Anti-parkinsonian activity of the adenosine A2A receptor antagonist/inverse agonist KW-6356 as monotherapy in MPTP-treated common marmosets.

KW-6356 is a novel adenosine A2A receptor antagonist/inverse agonist that not only blocks binding of adenosine to adenosine A2A receptor but also inhibits the constitutive activity of adenosine A2A receptor. The efficacy of KW-6356 as both monotherapy and an adjunct therapy to L-3,4-dihydroxyphenylalanine (L-DOPA)/decarboxylase inhibitor in Parkinson's disease (PD) patients has been reported. However, the first-generation A2A antagonist istradefylline, which is approved for use as an adjunct treatment to L-DOPA/decarboxylase inhibitor in adult PD patients experiencing OFF episodes, has not shown statistically significant efficacy as monotherapy. In vitro pharmacological studies have shown that the pharmacological properties of KW-6356 and istradefylline at adenosine A2A receptor are markedly different. However, the anti-parkinsonian activity and effects on dyskinesia of KW-6356 in PD animal models and the differences in the efficacy between KW-6356 and istradefylline are unknown. The present study investigated the anti-parkinsonian activity of KW-6356 as monotherapy in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets, and its efficacy was directly compared with that of istradefylline. In addition, we investigated whether or not repeated administration of KW-6356 induced dyskinesia. Oral administration of KW-6356 reversed motor disability in a dose-dependent manner up to 1 mg/kg in MPTP-treated common marmosets. The magnitude of anti-parkinsonian activity induced by KW-6356 was significantly greater than that of istradefylline. Repeated administration of KW-6356 induced little dyskinesia in MPTP-treated common marmosets primed to exhibit dyskinesia by prior exposure to L-DOPA. These results indicate that KW-6356 can be a novel non-dopaminergic therapy as monotherapy without inducing dyskinesia in PD patients.

Survival From Pediatric Out-of-Hospital Cardiac Arrest During Nights and Weekends: An Updated Japanese Registry-Based Study.

Background: Disparities in survival after pediatric out-of-hospital cardiac arrest (OHCA) between on-duty hours and off-duty hours have previously been reported. However, little is known about whether these disparities have remained in recent years. Objectives: This study aimed to examine the association of outcomes after pediatric OHCA with time of day and day of week. Methods: This observational study analyzed the Japanese government-led nationwide population-based registry data of OHCA patients. Pediatric (<18 years) patients who experienced OHCA between 2012 and 2017 were included. A multivariable logistic regression model was used to examine the association of both time of day (day/evening vs night) and day of week (weekday vs weekend) with outcomes after OHCA. The primary outcome was 1-month survival. Results: A total of 7,106 patients (mean age, 5.7 ± 6.5 years; 60.9% male) were included. 1,897 events (26.7%) occurred during night hours, and 2,096 events (29.5%) occurred on weekends. Overall, 1,192 (16.8%) survived 1 month after OHCA. After adjusting for potential confounders, 1-month survival during day/evening (1,047/5,209 [20.1%]) was significantly higher than that at night (145/1,897 [7.6%]) (adjusted odds ratio: 2.31 [95% CI: 1.87-2.86]), whereas there was no significant difference in 1-month survival between weekdays (845/5,010 [16.9%]) and weekends (347/2,096 [16.6%]) (adjusted odds ratio: 1.04 [95% CI: 0.88-1.23]). Conclusions: One-month survival after pediatric OHCA remained significantly lower during night than during day/evening, although disparities in 1-month survival between weekdays and weekends have been eliminated over time. Further studies are warranted to investigate the mechanisms underlying decreased survival at night.

Association between time to advanced airway management and survival during pediatric out-of-hospital cardiac arrest.

Background: Respiratory care, including advanced airway management (AAM), is an important part of pediatric resuscitation. This study aimed to determine whether time to AAM is associated with outcomes after out-of-hospital cardiac arrest (OHCA) in children. Methods: This was a nationwide population-based observational study using the Japanese government-led registry of OHCA patients. Children (aged 1-17 years) who experienced OHCA and received AAM by emergency medical service (EMS) personnel in the prehospital setting from 2014 to 2019 were included. Multivariable logistic regression models were used to assess the associations between time to AAM (defined as time in minutes from emergency call to the first successful AAM) and outcomes after OHCA. The primary outcome was one-month overall survival. The secondary outcomes were prehospital return of spontaneous circulation (ROSC) and one-month neurologically favorable survival. Results: A total of 761 patients (mean [SD] age, 12.7 [4.8] years) were included. The mean time to AAM was 18.9 min (SD, 7.9). Overall, 77 (10.1%) patients survived one month after OHCA. After adjusting for potential confounders, longer time to AAM was significantly associated with a decreased chance of one-month survival (multivariable adjusted OR per minute delay, 0.93 [95% CI, 0.89-0.97]; P = 0.001). Similar association was observed for prehospital ROSC (adjusted OR, 0.94 [95% CI, 0.90-0.99]; P = 0.01) and neurologically favorable survival (adjusted OR, 0.83 [95% CI, 0.72-0.95]; P = 0.006). This association between time to AAM and survival was consistent across a variety of sensitivity and subgroup analyses. Conclusions: Among pediatric OHCA patients, delayed AAM was associated with a decreased chance of survival, although the influence of resuscitation time bias might remain.

Epinephrine dosing interval and neurological outcome in out-of-hospital cardiac arrest.

OBJECTIVE: Current guidelines for cardiopulmonary resuscitation (CPR) recommend that standard-dose epinephrine be administered every 3-5 minutes during cardiac arrest. However, there is a knowledge gap regarding the optimal epinephrine dosing interval. This study aimed to examine the association between epinephrine dosing intervals and outcomes after out-of-hospital cardiac arrest (OHCA). METHODS: This was a nationwide population-based observational study using data from a Japanese government-led registry of OHCA, including patients who experienced OHCA in Japan from 2011 to 2017. We defined the epinephrine dosing interval as the time interval between the first epinephrine administration and return of spontaneous circulation in the prehospital setting, divided by the total number of epinephrine doses. The primary outcome was 1-month neurologically favorable survival. RESULTS: A total of 10,965 patients (mean (SD) age, 75.8 (14.3) years; 59.8% male) were included. The median epinephrine dosing interval was 3.5 minutes (IQR, 2.5-4.5; mean (SD), 3.6 (1.8)). Only approximately half of the patients received epinephrine administration with a standard dosing interval, as recommended in the current CPR guidelines. After multivariable adjustment, compared with the standard dosing interval, neither shorter nor longer epinephrine dosing intervals were associated with neurologically favorable survival after OHCA (Short vs Standard: adjusted OR 0.87 [95%CI 0.66-1.15]; and Long vs Standard: adjusted OR 1.08 [95%CI 0.76-1.55]). Similar associations were observed in propensity score-matched analyses. CONCLUSIONS: The epinephrine dosing interval was not associated with 1-month neurologically favorable survival after OHCA. Our findings do not deny the recommended epinephrine dosing interval in the current CPR guidelines.

Association of Nights and Weekends with Survival of Traumatic Out-of-Hospital Cardiac Arrest following Traffic Collisions: Japanese Registry-Based Study.

BACKGROUND: The process of care for traumatic out-of-hospital cardiac arrest (OHCA) may be different at night and on the weekend. However, little is known about whether the rate of survival after OHCA is affected by the time of day and day of the week. METHODS: This observational study analyzed the Japanese government-led nationwide population-based registry data of OHCA patients. Patients who experienced traumatic OHCA following traffic collisions from 2013 to 2017 were included in the study. A multivariable logistic regression model was used to examine the association of both time of day (day/evening vs. night) and day of the week (weekday vs. weekend) with outcomes after traumatic OHCA. Night was defined as 23:00 p.m. to 6:59 a.m., and weekends were defined as Saturday and Sunday. The primary outcome was one-month survival. RESULTS: A total of 8500 patients (mean [SD] age, 57.7 [22.3] years; 68.6% male) were included. 2267 events (26.7%) occurred at night, and 2482 events (29.2%) occurred on weekends. Overall, 173 patients (2.0%) survived one month after OHCA. After adjusting for potential confounders, one-month survival during the day/evening (148/6233 [2.4%]) was significantly higher than during the night (25/2267 [1.1%]) (adjusted OR, 1.95 [95%CI, 1.24-3.07]), whereas there was no significant difference in one-month survival between weekdays (121/6018 [2.0%]) and weekends (52/2482 [2.1%]) (adjusted OR, 0.97 [95%CI, 0.69-1.38]). CONCLUSIONS: One-month survival after traumatic OHCA was significantly lower during the night than during the day/evening, although there was no difference in one-month survival between weekdays and weekends. Further studies are warranted to investigate the underlying mechanisms of decreased survival at night.

Emphysematous gastritis.

An 89-year-old woman who had type 2 diabetes mellitus suddenly presented with abdominal pain. Abdominal computed tomography showed thickening of the wall and intramural gas in the gastric hilum, suggesting emphysematous gastritis. The patient underwent treatment with a proton-pump inhibitor and broad-spectrum antibacterial agents.

Association between time to advanced airway management and neurologically favourable survival during out-of-hospital cardiac arrest.

BACKGROUND: Advanced airway management (AAM) is commonly performed as part of advanced life support. However, there is controversy about the association between the timing of AAM and outcomes after out-of-hospital cardiac arrest (OHCA). This study aimed to determine whether time to AAM is associated with outcomes after OHCA. METHODS: This was a nationwide population-based observational study using the Japanese government-led registry of OHCA. Adults who experienced OHCA and received AAM by EMS personnel in the prehospital setting from 2014 to 2017 were included. Multivariable logistic regression models were used to assess the associations between time to AAM (defined as time in minutes from emergency call to the first successful AAM) and outcomes after OHCA. Then, associations between early (≤ 20 min) vs. delayed (> 20 min) AAM and outcomes after OHCA were examined using propensity score-matched analyses. The primary outcome was one-month neurologically favourable survival. RESULTS: A total of 164,223 patients (median [IQR] age, 80 [69-86] years; 57.7% male) were included. The median time to AAM was 17 min (IQR, 14-22). Longer time to AAM was significantly associated with a decreased chance of one-month neurologically favourable survival (multivariable adjusted OR per minute delay, 0.90 [95% CI, 0.90-0.91]). In the propensity score-matched cohort, compared with early AAM, delayed AAM was associated with a decreased chance of one-month neurologically favourable survival (516 of 50,997 [1.0%] vs. 226 of 50,997 [0.4%]; RR, 0.44; 95% CI, 0.37-0.51; NNT, 176). CONCLUSIONS: Delay in AAM was associated with a decreased chance of one-month neurologically favourable survival among patients with OHCA.

High diagnostic yield in skeletal ciliopathies using massively parallel genome sequencing, structural variant screening and RNA analyses.

Skeletal ciliopathies are a heterogenous group of disorders with overlapping clinical and radiographic features including bone dysplasia and internal abnormalities. To date, pathogenic variants in at least 30 genes, coding for different structural cilia proteins, are reported to cause skeletal ciliopathies. Here, we summarize genetic and phenotypic features of 34 affected individuals from 29 families with skeletal ciliopathies. Molecular diagnostic testing was performed using massively parallel sequencing (MPS) in combination with copy number variant (CNV) analyses and in silico filtering for variants in known skeletal ciliopathy genes. We identified biallelic disease-causing variants in seven genes: DYNC2H1, KIAA0753, WDR19, C2CD3, TTC21B, EVC, and EVC2. Four variants located in non-canonical splice sites of DYNC2H1, EVC, and KIAA0753 led to aberrant splicing that was shown by sequencing of cDNA. Furthermore, CNV analyses showed an intragenic deletion of DYNC2H1 in one individual and a 6.7 Mb de novo deletion on chromosome 1q24q25 in another. In five unsolved cases, MPS was performed in family setting. In one proband we identified a de novo variant in PRKACA and in another we found a homozygous intragenic deletion of IFT74, removing the first coding exon and leading to expression of a shorter message predicted to result in loss of 40 amino acids at the N-terminus. These findings establish IFT74 as a new skeletal ciliopathy gene. In conclusion, combined single nucleotide variant, CNV and cDNA analyses lead to a high yield of genetic diagnoses (90%) in a cohort of patients with skeletal ciliopathies.

Timing of Intravenous Epinephrine Administration During Out-of-Hospital Cardiac Arrest.

BACKGROUND: Current guidelines for cardiopulmonary resuscitation recommend that standard dose of epinephrine be administered every 3 to 5 min during cardiac arrest. However, there is controversy about the association between timing of epinephrine administration and outcomes after out-of-hospital cardiac arrest (OHCA). This study aimed to determine whether the timing of intravenous epinephrine administration is associated with outcomes after OHCA. METHODS: We analyzed Japanese government-led nationwide population-based registry data for OHCA. Adult OHCA patients who received intravenous epinephrine by emergency medical service personnel in the prehospital setting from 2011 to 2017 were included. Multivariable logistic regression models were used to assess the associations between time to first epinephrine administration and outcomes after OHCA. Subsequently, associations between early (≤20 min) versus delayed (>20 min) epinephrine administration and outcomes after OHCA were examined using propensity score-matched analyses. The primary outcome was 1-month neurologically favorable survival. RESULTS: A total of 119,946 patients (mean [SD] age, 75.2 [14.8] years; 61.4% male) were included. The median time to epinephrine was 23 min (interquartile range, 19-29). Longer time to epinephrine was significantly associated with a decreased chance of 1-month neurologically favorable survival (multivariable adjusted OR per minute delay, 0.91 [95% CI, 0.90-0.92]). In the propensity score-matched cohort, when compared with early (≤20 min) epinephrine, delayed (>20 min) epinephrine was associated with a decreased chance of 1-month neurologically favorable survival (959/42,804 [2.2%] vs. 330/42,804 [0.8%]; RR, 0.34; 95% CI, 0.30-0.39; NNT, 69). CONCLUSIONS: Delay in epinephrine administration was associated with a decreased chance of 1-month neurologically favorable survival among patients with OHCA.

Type of advanced airway and survival after pediatric out-of-hospital cardiac arrest.

BACKGROUND: There is a knowledge gap about advanced airway management (AAM) after pediatric out-of-hospital cardiac arrest (OHCA) in the prehospital setting. We assessed which AAM strategy would be associated with an increased chance of survival after pediatric OHCA. METHODS: A nationwide population-based observational study was conducted using the Japanese government-led registry data of OHCA. Pediatric OHCA patients (aged 1-17 years) who received prehospital AAM via endotracheal intubation (ETI) or supraglottic airway (SGA) insertion by emergency medical service (EMS) personnel from 2011 to 2017 were included. Patients who received ETI were compared with those who received SGA insertion. The primary outcome was one-month survival after OHCA. RESULTS: A total of 967 patients (mean [SD] age, 12.2 [5.1] years; 66.6% male) were included; 113 received ETI, and 854 received SGA insertion. Among the total cohort, 118 (12.2%) survived one month after OHCA. In the propensity score-matched cohort, no difference was observed in one-month survival between the ETI and SGA insertion groups: 13 of 113 patients (11.5%) vs 12 of 113 patients (10.6%); RR, 1.08; 95%CI, 0.52-2.27. This lack of association between AAM strategy and survival was observed across a variety of subgroup and sensitivity analyses, and also for neurologically favorable survival (P = 0.5611) in the propensity score-matched analysis. CONCLUSIONS: In Japan, among pediatric OHCA patients, there was no significant difference in one-month survival between prehospital ETI and SGA insertion by EMS personnel. Although an adequately powered randomized controlled trial is needed, EMS personnel may choose their familiar strategy when prehospital AAM was performed during pediatric OHCA.

Bystander-initiated conventional vs compression-only cardiopulmonary resuscitation and outcomes after out-of-hospital cardiac arrest due to drowning.

BACKGROUND: Great emphasis has been placed on rescue breathing in out-of-hospital cardiac arrest (OHCA) due to drowning. However, there is no evidence about the effect of rescue breathing on neurologically favorable survival after OHCA due to drowning. The aim of this study is to examine the effect of bystander-initiated conventional (with rescue breathing) versus compression-only (without rescue breathing) cardiopulmonary resuscitation (CPR) in OHCA due to drowning. METHODS: This nationwide population-based observational study using prospectively collected government-led registry data included patients with OHCA due to drowning who were transported to an emergency hospital in Japan between 2013 and 2016. The primary outcome was one-month neurologically favorable survival. RESULTS: The full cohort (n = 5121) comprised 2486 (48.5%) male patients, and the mean age was 72.4 years (standard deviation, 21.6). Of these, 968 (18.9%) received conventional CPR, and 4153 (81.1%) received compression-only CPR. 928 patients receiving conventional CPR were propensity-matched with 928 patients receiving compression-only CPR. In the propensity score-matched cohort, one-month neurologically favorable survival was not significantly different between the two groups (7.5% in the conventional CPR group vs. 6.6% in the compression-only CPR group; risk ratio, 1.15; 95% confidence interval, 0.82-1.60; P = 0.4147). This association was consistent across a variety of subgroup analyses. CONCLUSIONS: Among patients with OHCA due to drowning, there were no differences in one-month neurologically favorable survival between bystander-initiated conventional and compression-only CPR groups, although several important data (e.g., water temperature, submersion duration, or body of water) could not be addressed. Further study is warranted to confirm our findings.

Association of bystander cardiopulmonary resuscitation and neurological outcome after out-of-hospital cardiac arrest due to drowning in Japan, 2013-2016.

BACKGROUND: Early initiation of cardiopulmonary resuscitation (CPR) performed by bystanders is essential in patients with out-of-hospital cardiac arrest (OHCA) due to primary cardiac cause. However, evidence about the effect of bystander CPR on neurologically favorable survival after OHCA due to drowning is scarce and controversial. METHODS: This nationwide population-based observational study using prospectively collected government-led registry data included patients with OHCA due to drowning who were transported to an emergency hospital between 2013 and 2016. The primary outcome was one-month neurologically favorable survival defined as Glasgow-Pittsburgh Cerebral Performance Category score of 1-2. The secondary outcomes were one-month survival and prehospital return of spontaneous circulation (ROSC). RESULTS: The full cohort (n = 12,139) comprised 6291 (51.8%) male patients, and the mean age was 73.7 (standard deviation [SD], 18.8). Of these, 5157 (42.5%) received bystander CPR, and 6982 (57.5%) did not. 4345 patients receiving bystander CPR were propensity-matched with 4345 patients not receiving bystander CPR. In the propensity score-matched cohort, bystander CPR was associated with increased chance of one-month neurologically favorable survival (0.4% vs. 0.8%; risk ratio [RR], 2.19; 95%confidence interval [CI], 1.21-3.95; P = 0.0076), one-month survival (1.1% vs. 1.7%; RR, 1.55; 95%CI, 1.09-2.22; P = 0.0150), and prehospital ROSC (2.7% vs. 3.5%; RR, 1.30; 95%CI, 1.03-1.65; P = 0.0296). Similar association was observed across a variety of sensitivity analyses. In subgroup analysis, statistically significant difference was not observed in pediatric OHCA due to drowning, although the sample size was too small (n = 218). CONCLUSIONS: Among patients with OHCA due to drowning, bystander CPR was associated with increased chance of neurologically favorable survival.

Radiation Monitoring of an Isolation Room for 131I Therapy After the Patients Were Released.

PURPOSE: This study was performed to obtain a better understanding of the radiation environment in an I isolation room after the release of patients with metastasis from thyroid cancer that were treated with I doses ranging from 3.7 GBq (100 mCi) to 5.5 GBq (150 mCi) because there have not been any previous studies regarding the ambient radiation levels encountered in I isolation rooms after patients are released. METHODS: Ambient radiation levels and total and removable surface contamination levels were monitored for 3 weeks after each patient's release (and before the entry of the next patient). An area located 0.75 m along the corridor outside the room, the door, window, bedside, and the wall of the shower room were monitored with a Nal scintillation survey meter, which was used to obtain readings of the ambient radiation level in six directions, and the mean value for each area was recorded. In addition, areas that were suspected to be highly contaminated, including the toilet bowl, toilet sink, bed head, back of the bed, sink, trash box, and the patient's pillow, were monitored for total surface contamination with a GM survey meter. Furthermore, the toilet's U-bend, toilet sink, bed guard, table, shielding, sink plug, and door knob were swabbed for monitoring removable surface contamination, which was measured using a well counter. CONCLUSION: Ambient radiation monitoring in an I isolation room showed that there was negligible risk of harm in terms of the occupational radiation dose level after patients were released. The ambient radiation dose rate was higher near the door because the sink and trash box were located nearby. The toilet bowl, the toilet's U-bend, and the area around the sink exhibited heavy surface contamination, so these areas require cautious hygiene management.

Association of Prehospital Advanced Life Support by Physician With Survival After Out-of-Hospital Cardiac Arrest With Blunt Trauma Following Traffic Collisions: Japanese Registry-Based Study.

Importance: Controversy remains as to whether advanced life support (ALS) or basic life support (BLS) is superior for critically ill and injured patients, including out-of-hospital cardiac arrest (OHCA) and major trauma, in the prehospital setting. Objective: To assess whether prehospital ALS should be provided for traumatic OHCA and who should perform it. Design, Setting, and Participants: Japanese government-managed nationwide population-based registry data of patients with OHCA transported to an emergency hospital were analyzed. Patients who experienced traumatic OHCA following a traffic collision from 2013 to 2014 were included. Patients provided prehospital ALS by a physician were compared with both patients provided ALS by emergency medical service (EMS) personnel and patients with only BLS. The data were analyzed on May 1, 2017. Exposures: Advanced life support by physician, ALS by EMS personnel, or BLS only. Main Outcomes and Measures: The primary outcome was 1-month survival. The secondary outcomes were prehospital return of spontaneous circulation and favorable neurologic outcomes with the Glasgow-Pittsburgh cerebral performance category score of 1 or 2. Results: A total of 4382 patients were included (mean [SD] age, 57.5 [22.2] years; 67.9% male); 828 (18.9%) received prehospital ALS by physician, 1591 (36.3%) received prehospital ALS by EMS personnel, and 1963 (44.8%) received BLS only. Among these patients, 96 (2.2%) survived 1 month after OHCA, including 26 of 828 (3.1%) for ALS by physician, 25 of 1591 (1.6%) for ALS by EMS personnel, and 45 of 1963 (2.3%) for BLS. After adjusting for potential confounders using multivariable logistic regression, ALS by physician was significantly associated with higher odds for 1-month survival compared with both ALS by EMS personnel and BLS (adjusted OR, 2.13; 95% CI, 1.20-3.78; and adjusted OR, 1.94; 95% CI, 1.14-3.25; respectively), whereas there was no significant difference between ALS by EMS personnel and BLS (adjusted OR, 0.91; 95% CI, 0.54-1.51). A propensity score-matched analysis in the ALS cohort showed that ALS by physician was associated with increased chance of 1-month survival compared with ALS by EMS personnel (risk ratio, 2.00; 95% CI, 1.01-3.97; P = .04). This association was consistent across a variety of sensitivity analyses. Conclusions and Relevance: In traumatic OHCA, ALS by physician was associated with increased chance of 1-month survival compared with both ALS by EMS personnel and BLS.

Effect of prehospital advanced airway management for pediatric out-of-hospital cardiac arrest.

BACKGROUND: Respiratory care may be important in pediatric out-of-hospital cardiac arrest (OHCA) due to the asphyxial nature of the majority of events. However, evidence of the effect of prehospital advanced airway management (AAM) for pediatric OHCA is scarce. METHODS: This was a nationwide population-based study of pediatric OHCA in Japan from 2011 to 2012 based on data from the All-Japan Utstein Registry. We included pediatric OHCA patients aged between 1 and 17 years old. The primary outcome was one-month neurologically favorable survival defined as a Glasgow-Pittsburgh cerebral performance category (CPC) score of 1-2 (corresponding to a Pediatric CPC score of 1-3). RESULTS: A total of 2157 patients were included in the final cohort; 365 received AAM and 1792 received bag-valve-mask (BVM) ventilation only. Among the 2157 patients, 213 (9.9%) survived with favorable neurological outcomes (CPC of 1-2) one month after OHCA. There were no significant differences in neurologically favorable survival between the AAM and BVM groups after adjusting for potential confounders, although there was a tendency favoring BVM ventilation: propensity score matching, OR 0.74 (95%CI 0.35-1.59), and multivariable logistic regression modeling, ORadjusted 0.55 (95%CI 0.24-1.14). Subgroup analyses demonstrated that there were no subgroups in which AAM was associated with neurologically favorable survival, including the non-cardiac (primarily asphyxial) etiology group. CONCLUSIONS: In pediatric OHCA, prehospital AAM was not associated with an increased chance of neurologically favorable survival compared with BVM-only ventilation. However, careful consideration is required to interpret the findings, as there may be unmeasured residual confounders and selection bias.

Public access defibrillation and outcomes after pediatric out-of-hospital cardiac arrest.

BACKGROUND: Use of automated external defibrillators (AEDs) has been recommended for pediatric out-of-hospital cardiac arrest (OHCA). However, there are no conclusive studies that elucidated the effectiveness of public-access defibrillation (PAD) in children. METHODS: This was a nationwide, population-based, propensity score-matched study of pediatric OHCA in Japan from 2011 to 2012, based on data from the All-Japan Utstein Registry. We included pediatric OHCA patients (aged 1-17 years) who received bystander cardiopulmonary resuscitation. The primary outcome was a favorable neurological state 1 month after OHCA (defined as a CPC score of 1-2). RESULTS: A total of 1193 patients were included in the final cohort; 57 received PAD and 1136 did not. Among 1193 patients, 188 (15.8%) survived with a favorable neurological status 1 month after OHCA. The odds of neurologically favorable survival were significantly higher for patients receiving PAD after adjusting for potential confounders: propensity score matching, OR 3.17 (95% CI 1.40-7.17), and multivariable logistic regression modeling, ORadjusted 5.10 (95% CI 2.01-13.70). Similar findings were observed for the secondary outcomes (i.e., neurologically favorable survival with a CPC score of 1, one-month survival, and prehospital return of spontaneous circulation). In subgroup analyses, there were no significant differences in neurologically favorable survival between the PAD group and non-PAD group in the unwitnessed cohort (ORadjusted 7.76 [0.75-81.90]) or the non-cardiac etiology cohort (ORadjusted 6.65 [0.64-66.24]). CONCLUSIONS: PAD was associated with an increased chance of neurologically favorable survival in pediatric OHCA (aged 1-17 years) who received bystander CPR, except for in cases of unwitnessed or non-cardiac etiology.

Effect of rescue breathing by lay rescuers for out-of-hospital cardiac arrest caused by respiratory disease: a nationwide, population-based, propensity score-matched study.

The importance of respiratory care in cardiopulmonary resuscitation may vary depending on the cause of cardiac arrest. No previous study has investigated the effects of rescue breathing performed by a lay rescuer on the outcomes of patients with out-of-hospital cardiac arrest (OHCA) caused by intrinsic respiratory diseases. The aim of this study was to investigate whether rescue breathing performed by a lay rescuer is associated with outcomes after respiratory disease-related OHCA. In a nationwide, population-based, propensity score-matched study in Japan, among adult patients with OHCA caused by respiratory disease who received bystander cardiopulmonary resuscitation from January 1, 2005 to December 31, 2010, we compared patients with rescue breathing to those without rescue breathing. The primary outcome was neurologically favorable survival 1 month after OHCA. Of the eligible 14,781 patients, 4970 received rescue breathing from a lay rescuer and 9811 did not receive rescue breathing. In a propensity score-matched cohort (4897 vs. 4897 patients), the neurologically favorable survival rate was similar between patients with and without rescue breathing from a lay rescuer [0.9 vs. 0.7 %; OR 1.23 (95 % CI 0.79-1.93)]. Additionally, in subgroup analyses, rescue breathing was not associated with neurological outcome regardless of the type of rescuer [family member: adjusted OR 0.83 (95 % CI 0.39-1.70); or non-family member: adjusted OR 1.91 (95 % CI 0.79-5.35)]. Even among patients with OHCA caused by respiratory disease, rescue breathing performed by a lay rescuer was not associated with neurological outcomes, regardless of the type of lay rescuer.

Conventional Versus Compression-Only Versus No-Bystander Cardiopulmonary Resuscitation for Pediatric Out-of-Hospital Cardiac Arrest.

BACKGROUND: Conventional cardiopulmonary resuscitation (CPR) (chest compression and rescue breathing) has been recommended for pediatric out-of-hospital cardiac arrest (OHCA) because of the asphyxial nature of the majority of pediatric cardiac arrest events. However, the clinical effectiveness of additional rescue breathing (conventional CPR) compared with compression-only CPR in children is uncertain. METHODS: This nationwide population-based study of pediatric OHCA patients was based on data from the All-Japan Utstein Registry. We included all pediatric patients who experienced OHCA in Japan from January 1, 2011, to December 31, 2012. The primary outcome was a favorable neurological state 1 month after OHCA defined as a Glasgow-Pittsburgh Cerebral Performance Category score of 1 to 2 (corresponding to a Pediatric Cerebral Performance Category score of 1-3). Outcomes were compared with logistic regression with uni- and multivariable modeling in the overall cohort and for a propensity-matched subset of patients. RESULTS: A total of 2157 patients were included; 417 received conventional CPR, 733 received compression-only CPR, and 1007 did not receive any bystander CPR. Among these patients, 213 (9.9%) survived with a favorable neurological status 1 month after OHCA, including 108/417 (25.9%) for conventional, 68/733 (9.3%) for compression-only, and 37/1007 (3.7%) for no-bystander CPR. In unadjusted analyses, conventional CPR was superior to compression-only CPR in neurologically favorable survival (odds ratio [OR] 3.42, 95% confidence interval [CI] 2.45-4.76; P<0.0001), with a trend favoring conventional CPR that was no longer statistically significant after multivariable adjustment (ORadjusted 1.52, 95% CI 0.93-2.49), and with further attenuation of the difference in a propensity-matched subset (OR 1.20, 95% CI 0.81-1.77). Both conventional and compression-only CPR were associated with higher odds for neurologically favorable survival compared with no-bystander CPR (ORadjusted 5.01, 95% CI 2.98-8.57, and ORadjusted 3.29, 95% CI 1.93-5.71), respectively. CONCLUSIONS: In this population-based study of pediatric OHCA in Japan, both conventional and compression-only CPR were associated with superior outcomes compared with no-bystander CPR. Unadjusted outcomes with conventional CPR were superior to compression-only CPR, with the magnitude of difference attenuated and no longer statistically significant after statistical adjustments. These findings support randomized clinical trials comparing conventional versus compression-only CPR in children, with conventional CPR preferred until such controlled comparative data are available, and either method preferred over no-bystander CPR.

Effect of prehospital epinephrine on out-of-hospital cardiac arrest: a report from the national out-of-hospital cardiac arrest data registry in Japan, 2011-2012.

PURPOSE: The effect of prehospital epinephrine on neurological outcome in out-of-hospital cardiac arrest (OHCA) is still controversial. We sought to determine whether prehospital epinephrine administration was associated with improved outcomes in adult OHCA. METHODS: A nationwide, population-based, propensity score-matched study of OHCA patients from January 1, 2011, to December 31, 2012, in Japan was conducted. We included adult OHCA patients treated by emergency medical service personnel without an excessive delay. The primary outcome was neurologically favorable survival 1 month after OHCA. RESULTS: A total of 237,068 patients (16,616 with a shockable rhythm and 220,452 with a non-shockable rhythm) were included in the final cohort. A total of 4024 out of the 16,616 shockable OHCAs and 29,393 out of the 220,452 non-shockable OHCAs received prehospital epinephrine. In the propensity score-matched cohort, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival (shockable OHCA 7.6 vs. 17.9 %, OR 0.38 [95%CI 0.33-0.43]; non-shockable OHCA 0.6 vs. 1.2 %, OR 0.47 [95%CI 0.39-0.56]). In the subgroup analyses, prehospital epinephrine was significantly associated with poor neurological outcome in all subgroups. In the ancillary analyses, although the neurological outcome was worse as the number of epinephrine doses increased or the time to epinephrine increased, patients had a greater chance of a favorable neurological outcome only when a single dose of epinephrine was administered within 15 min of the emergency call in shockable OHCA. CONCLUSIONS: Among adult OHCA patients, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival. Situations in which prehospital epinephrine is effective may be extremely limited.

Epidemiology, Risk Factors, and Outcomes of Out-of-Hospital Cardiac Arrest Caused by Stroke: A Population-Based Study.

Limited information is available regarding stroke-related out-of-hospital cardiac arrest (OHCA). We aimed to assess the clinical characteristics of stroke-related OHCA and to identify the factors associated with patient outcomes.We conducted a nationwide population-based study of adult OHCA patients in Japan from January 1, 2006 to December 31, 2009. We examined the epidemiology, risk factors, and outcomes of stroke-related OHCA compared with cardiogenic OHCA. The primary outcome was neurologically favorable survival.Of the 243,140 eligible patients, 18,682 (7.7%) were diagnosed with stroke-related OHCA. Compared to OHCA with a presumed cardiac etiology, stroke-related OHCA patients had a greater chance of prehospital return of spontaneous circulation (ROSC) (9.9% vs 5.9%, P < 0.0001) but a reduced chance of 1-month survival (3.6% vs 4.9%, P < 0.0001) or favorable neurological outcomes (1.2% vs 2.6%, P < 0.0001). After adjusting for a variety of confounding factors, the prehospital ROSC rates were higher (adjusted OR 2.47, 95% confidence interval [CI] 2.34-2.62), but the neurologically favorable survival rates were lower (adjusted OR 0.66, 95%CI 0.57-0.76), among the stroke-related OHCA patients. In stroke-related OHCA cases, having a younger age, witness, and shockable 1st documented rhythm were associated with improved outcomes. Men had more favorable neurological outcomes. Seasonal or circadian factors had no critical impact on favorable neurological outcomes. Prehospital advanced life support techniques (i.e., epinephrine administration or advanced airway management) were not associated with favorable neurological outcomes.Although stroke-related OHCA had lower 1-month survival rates and poorer neurological outcomes than cardiogenic OHCA, the rates were not considered to be medically futile. Characteristically, sex differences might impact neurologically favorable survival.