Influence of hospital capabilities and prehospital time on outcomes of thrombectomy for stroke in Japan from 2013 to 2016.

To determine whether increasing thrombectomy-capable hospitals with moderate comprehensive stroke center (CSC) capabilities is a valid alternative to centralization of those with high CSC capabilities. This retrospective, nationwide, observational study used data from the J-ASPECT database linked to national emergency medical service (EMS) records, captured during 2013-2016. We compared the influence of mechanical thrombectomy (MT) use, the CSC score, and the total EMS response time on the modified Rankin Scale score at discharge among patients with acute ischemic stroke transported by ambulance, in phases I (2013-2014, 1461 patients) and II (2015-2016, 3259 patients). We used ordinal logistic regression analyses to analyze outcomes. From phase I to II, MTs increased from 2.7 to 5.5%, and full-time endovascular physicians per hospital decreased. The CSC score and EMS response time remained unchanged. In phase I, higher CSC scores were associated with better outcomes (1-point increase, odds ratio [95% confidence interval]: 0.951 [0.915-0.989]) and longer EMS response time was associated with worse outcomes (1-min increase, 1.007 [1.001-1.013]). In phase II, neither influenced the outcomes. During the transitional shortage of thrombectomy-capable hospitals, increasing hospitals with moderate CSC scores may increase nationwide access to MT, improving outcomes.

Inconsistency in the Standard of Care-Toward Evidence-Based Management of Exertional Heat Stroke.

Tokyo 2020 Summer Olympics are projected to experience environmental heat stress that surpasses the environmental conditions observed in the Atlanta (1996), Athens (2004), Beijing (2008), and Rio (2016) Summer Olympics. This raises particular concerns for athletes who will likely to be exposed to extreme heat during the competitions. Therefore, in mass-participation event during warm season, it is vital for the hosting organization to build preparedness and resilience against heat, including appropriate treatment, and management strategies for exertional heat stroke (EHS). However, despite the existing literature regarding the evidence-based management of EHS, rectal thermometry and whole-body cold-water immersion are not readily accepted by medical professionals outside of the sports, and military medicine professionals. Current Japanese medical standard is no exception in falling behind on evidence-based management of EHS. Therefore, the first aim of this paper is to elucidate the inconsistency between the standard of care provided in Japan for EHS and what has been accepted as the gold standard by the scientific literature. The second aim of this paper is to provide optimal EHS management strategies that should be implemented at the Tokyo 2020 Summer Olympics from organizational level to maximize the safety of athletes and to improve organizational resilience to heat. The risk of extreme heat is often neglected until a catastrophic incidence occurs. It is vital for the Japanese medical leadership and athletic communities to re-examine the current EHS management strategies and implement evidence-based countermeasure for EHS to expand the application of scientific knowledge.

Grand Sumo Tournaments and Out-of-Hospital Cardiac Arrests in Tokyo.

BACKGROUND: Sumo wrestling is a demanding sport. Although watching sumo wrestling may have cardiovascular effects, no studies of this relationship have been performed. Thus, we aimed to evaluate the association between sumo wrestling tournaments and the rate of out-of-hospital cardiac arrests. METHODS AND RESULTS: We counted the daily number of patients aged 18 to 110 years who had an out-of-hospital cardiac arrest of presumed-cardiac origin in the Tokyo metropolis between 2005 and 2014. A Poisson regression was used to model out-of-hospital cardiac arrests of presumed-cardiac origin per day. Exposure days were the days on which a sumo tournament was held and broadcast, whereas control days were all other days. Events that occurred on exposure days were compared with those that occurred on control days. Risk ratios for out-of-hospital cardiac arrests on Grand Sumo tournaments days compared with control days were estimated. In total, 71 882 out-of-hospital cardiac arrests met the inclusion criteria. We recorded a 9% increase in the occurrence of out-of-hospital cardiac arrests on the day of a sumo tournament compared with control days. In patients aged 75 to 110 years, we found a 13% increase in the occurrence of out-of-hospital cardiac arrests on the day of a sumo tournament compared with control days. CONCLUSIONS: We found a significant increase in the occurrence of out-of-hospital cardiac arrests on the days of sumo tournaments compared with control days in the Tokyo metropolis between 2005 and 2014. Further studies are needed to verify these initial findings on sumo tournaments and cardiovascular events.

Dispatcher-assisted bystander cardiopulmonary resuscitation and survival in out-of-hospital cardiac arrest.

INTRODUCTION: Bystander cardiopulmonary resuscitation (CPR) is critical to the survival of patients with out-of-hospital cardiac arrest (OHCA). However, it is unknown whether bystander CPR with or without dispatcher assistance is more effective or why. Thus, we evaluated the association between dispatcher-assisted bystander CPR (vs. bystander CPR without dispatcher assistance) and survival of patients with OHCA. METHODS: This is a retrospective, nonrandomized, observational study using national registry data for all OHCAs. We performed a propensity analysis. Patients with OHCA of cardiac origin were 18-100 years of age and received bystander chest compression in Japan between 2005 and 2014. Outcome measures were bystander rescue breathing, return of spontaneous circulation (ROSC) before hospital arrival, and survival and Cerebral Performance Category (CPC) 1 or 2 at 1 month after the event. RESULTS: During the study period, 1,176,351 OHCAs occurred, and 87,400 cases met the inclusion criteria. Among propensity-matched patients, a negative association was observed between dispatcher-assisted bystander CPR and outcome measures in a fully-adjusted model [odds ratio (OR) (95% CI) for ROSC = 0.87 (0.78-0.97), P < 0.05; OR (95% CI) for 1-month survival = 0.81 (0.65-1.00), P < 0.05; OR (95% CI) for CPC 1 or 2 = 0.64 (0.43-0.93), P < 0.05]. OR of survival for dispatcher-assisted bystander CPR tended to decrease as the emergency medical services response time increased. CONCLUSIONS: Survival benefit was less for dispatcher-assisted bystander CPR with dispatcher assistance than without dispatcher assistance. Low quality is hypothesized to be the cause of the reduced benefit.

Interaction of defibrillation waveform with the time to defibrillation or the number of defibrillation attempts on survival from out-of-hospital cardiac arrest.

AIM: Early biphasic defibrillation is effective in out-of-hospital cardiac arrest (OHCA) cases. In the resuscitation of patients with OHCA, it is not clear how the defibrillation waveform interacts with the time to defibrillation to influence patient survival. The second, and any subsequent, shocks need to be administered by an on-line physician in Japan. Thus, we investigated the interaction between the defibrillation waveform and time to or the number of defibrillation on resuscitation outcomes. METHODS: This prospective observational study used data for all OHCAs that occurred between 2005 and 2014 in Japan. To investigate the interaction effect between the defibrillation waveform and the time to defibrillation or the number of defibrillations on the return to spontaneous circulation (ROSC), 1-month survival, and cerebral performance category (CPC) (1, 2), we assessed the modifying effects of the defibrillation waveform and the time to or the number of defibrillation on additive scale (i.e., the relative excessive risk due to interaction, RERI) and multiplicative scale (i.e., ratio of odds ratios (ORs)). RESULTS: In total, 71,566 cases met the inclusion criteria. For the measure of interaction between the defibrillation waveform and the time to defibrillation, ratio of ORs for ROSC was 0.84 (0.75-0.94), implying that the effect of time to first defibrillation on ROSC was negatively modified by defibrillation waveform. For the interaction between the defibrillation waveform and the number of defibrillations, RERI and ratio of ORs for CPC (1, 2) was -0.25 (-0.47 to -0.06) and 0.79 (0.67-0.93), respectively. It is implied that the effect of number of defibrillation on CPC (1, 2) was negatively modified by defibrillation waveform. CONCLUSIONS: An increased number of defibrillations was associated with a decreased ROSC in the case of biphasic and monophasic defibrillation, while an increased number of defibrillations was related to an increased 1-month survival rate and CPC (1, 2) only in the case of biphasic defibrillation. When two or more defibrillations were performed, a biphasic waveform was more effective in terms of long-term survival than a monophasic waveform.

Effects of advanced life support on patients who suffered cardiac arrest outside of hospital and were defibrillated.

BACKGROUND: The effects and relative benefits of advanced airway management and epinephrine on patients with out-of-hospital cardiac arrest (OHCA) who were defibrillated are not well understood. METHODS: This was a prospective observational study. Using data of all out-of-hospital cardiac arrest cases occurring between 2005 and 2013 in Japan, hierarchical logistic regression and conditional logistic regression along with time-dependent propensity matching were performed. Outcome measures were survival and minimal neurological impairment [cerebral performance category (CPC) 1 or 2] at 1month after the event. RESULTS: We analyzed 37,873 cases that met the inclusion criteria. Among propensity-matched patients, advanced airway management and/or prehospital epinephrine use was related to decreased rates of 1-month survival (adjusted odds ratio 0.88, 95% confidence interval 0.80 to 0.97) and CPC (1, 2) (adjusted odds ratio 0.56, 95% confidence interval 0.48 to 0.66). Advanced airway management was related to decreased rates of 1-month survival (adjusted odds ratio 0.89, 95% confidence interval 0.81to 0.98) and CPC (1, 2) (adjusted odds ratio 0.54, 95% confidence interval 0.46 to 0.64) in patients who did not receive epinephrine, whereas epinephrine use was not related to the outcome measures. CONCLUSIONS: In defibrillated patients with OHCA, advanced airway management and/or epinephrine are related to reduced long-term survival, and advanced airway management is less beneficial than epinephrine. However, the proportion of patients with OHCA who responded to an initial shock was very low in the study subjects, and the external validity of our findings might be limited.

Age × Gender Interaction Effect on Resuscitation Outcomes in Patients With Out-of-Hospital Cardiac Arrest.

Although an interaction between gender and age has been shown to influence resuscitation outcomes in patients with out-of-hospital cardiac arrest (OHCA), this interaction has not been investigated in Asian populations. In this prospective, observational study, data from all cases of OHCA in Japan between 2005 and 2012 were obtained from the Japanese National Registry. We determined the relative excess risk due to interaction and the ratio of odds ratios (ORs) to assess the interaction effect of gender and age on the incidence of return of spontaneous circulation (ROSC) before hospital arrival, 1-month survival, and neurologically intact survival 1 month after OHCA. Male gender was associated with decreased ROSC and lower 1-month survival rates in patients with OHCA of presumed cardiac origin. Older age was associated with lower 1-month and neurologically intact survival rates in male patients with OHCA of presumed cardiac and noncardiac origin and with increased ROSC in male patients with OHCA of presumed cardiac origin. The relative excess risk due to interaction for ROSC in patients with OHCA of presumed cardiac origin was statistically significant (OR 0.19, 95% confidence interval [CI] 0.06 to 0.32). The ratio of ORs for ROSC was statistically significant in patients with OHCA of presumed cardiac origin (OR 1.25, 95% CI 1.05 to 1.47) and of noncardiac origin (OR 0.40, 95% CI 0.17 to 0.92). In conclusion, the interaction effect between age and gender on ROSC was positive in OHCA cases of presumed cardiac origin and negative in those of noncardiac origin.

Successful Hospital Evacuation After the Kumamoto Earthquakes, Japan, 2016.

Two major earthquakes struck Kumamoto Prefecture in Japan in April 2016. Disaster response was immediately provided, including disaster medical services. Many hospitals were damaged and patients needed immediate evacuation to alternative facilities. The hospital bed capacity of Kumamoto Prefecture was overwhelmed, and transportation of more than 100 patients was needed. Hospital evacuation was carried out smoothly with the coordinated efforts of multiple agencies. The overall operation was deemed a success because patients were transported in a timely manner without any significant adverse events. Upon repair of facilities in Kumamoto Prefecture, patients were returned safely to their previous facilities. The management of inpatients after this natural disaster in Kumamoto Prefecture can serve as a model for hospital evacuation with multi-agency coordination in the future. Future efforts are needed to improve interfacility communications immediately following a natural disaster. (Disaster Med Public Health Preparedness. 2017;11:517-521).

Factors associated with the outcome of out-of-hospital cardiopulmonary arrest among people over 80 years old in Japan.

AIM: To determine if termination of resuscitation should be considered for older individuals, we sought to identify factors associated with clinical outcome following out-of-hospital cardiac arrest (OHCA) in people ≥80 years old and over. METHODS: A prospective, population-based, observational study was conducted for ≥80-year-old individuals who experienced out-of-hospital cardiac arrest and to whom resuscitation was provided by emergency responders between January 1, 2005 and December 31, 2012 (n=377,577). The primary endpoint was 1-month survival. Signal detection analysis was applied to estimate predictive factors among 17 variables. RESULTS: Among all out-of-hospital cardiac arrest cases, 59.4% were of cardiac origin, and 1-month survival rate was 3.3%. Following signal detection analysis, cases of both cardiac and non-cardiac origin were categorized into three subgroups defined by return of spontaneous circulation (ROSC) and epinephrine use. One-month survival ranged between 1.2 and 41.0% for the three subgroups of cardiac origin and between 2.0 and 41.1% for the three subgroups of non-cardiac origin. CONCLUSIONS: ROSC was the most significant predictor of 1-month survival among patients with cardiac and non-cardiac OHCA who were ≥80 years old. Absence of ROSC might be an important factor to the termination of resuscitation rule for OHCA in individuals who are ≥80years old.

Resuscitation outcomes of reproductive-age females who experienced out-of-hospital cardiac arrest.

BACKGROUND: Although some studies have shown that women in their reproductive years have better resuscitation outcomes of out-of-hospital cardiac arrest (OHCA), conflicting results and methodological problems have also been noted. Thus, we evaluated the resuscitation outcomes of OHCA of females by age. METHODS: This was a prospective observational study using registry data from all OHCA cases between 2005 and 2012 in Japan. The subjects were females aged 18-110 years who suffered an out-of-hospital cardiac arrest. Logistic regression analyses were performed using total and propensity-matched patients. RESULTS: There were 381,123 OHCA cases that met the inclusion criteria. Among propensity-matched patients, females aged 18-49 and 50-60 years of age had similar rates of return of spontaneous circulation before hospital arrival and 1-month survival (all p>0.60). In contrast, females aged 18-49 years of age had significantly lower rates of 1-month survival with minimal neurological impairment than did females aged 50-60 years of age (after adjusting for selected variables: Cerebral Performance Category scale 1 or 2 (CPC (1, 2)), OR=0.45, p=0.020; Overall Performance Category scale 1 or 2 (OPC (1, 2)): OR=0.42, p= 0.014; after adjustment for all variables: CPC (1, 2), OR=0.27, p= 0.008; OPC (1, 2), OR=0.29, p=0.009). CONCLUSION: Women of reproductive age did not show improved resuscitation outcomes in OHCA. Additionally, women in their reproductive years showed worse neurological outcomes one month after the event, which may be explained by the negative effects of estrogen. These findings need to be verified in further studies.

Ambulance Dispatches From Unaffected Areas After the Great East Japan Earthquake: Impact on Emergency Care in the Unaffected Areas.

OBJECTIVE: Although dispatching ambulance crews from unaffected areas to a disaster zone is inevitable when a major disaster occurs, the effect on emergency care in the unaffected areas has not been studied. We evaluated whether dispatching ambulance crews from unaffected prefectures to those damaged by the Great East Japan Earthquake was associated with reduced resuscitation outcomes in out-of-hospital cardiac arrest (OHCA) cases in the unaffected areas. METHODS: We used the Box-Jenkins transfer function model to assess the relationship between ambulance crew dispatches and return of spontaneous circulation (ROSC) before hospital arrival or 1-month survival after the cardiac event. RESULTS: In a model whose output was the rate of ROSC before hospital arrival, dispatching 1000 ambulance crews was associated with a 0.474% decrease in the rate of ROSC after the dispatch in the prefectures (p=0.023). In a model whose output was the rate of 1-month survival, dispatching 1000 ambulance crews was associated with a 0.502% decrease in the rate of 1-month survival after the dispatch in the prefectures (p=0.011). CONCLUSIONS: The dispatch of ambulances from unaffected prefectures to earthquake-stricken areas was associated with a subsequent decrease in the ROSC and 1-month survival rates in OHCA cases in the unaffected prefectures.

The number of prehospital defibrillation shocks and 1-month survival in patients with out-of-hospital cardiac arrest.

BACKGROUND: The relationship between the number of pre-hospital defibrillation shocks and treatment outcome in patients with out-of-hospital cardiac arrest (OHCA) presenting with ventricular fibrillation (VF) is unknown currently. We examined the association between the number of pre-hospitalization defibrillation shocks and 1-month survival in OHCA patients. METHODS: We conducted a prospective observational study using national registry data obtained from patients with OHCA between January 1, 2009 and December 31, 2012 in Japan. The study subjects were ≥ 18-110 years of age, had suffered from an OHCA before arrival of EMS personnel, had a witnessed collapse, had an initial rhythm that was shockable [VF/ventricular tachycardia (pulseless VT)], were not delivered a shock using a public automated external defibrillator (AED), received one or more shocks using a biphasic defibrillator by EMS personnel, and were transported to a medical institution between January 1, 2009 and December 31, 2012. There were 20,851 OHCA cases which met the inclusion criteria during the study period. Signal detection analysis was used to identify the cutoff point in the number of prehospital defibrillation shocks most closely related to one-month survival. Variables related to the number of defibrillations or one-month survival in OHCA were identified using multiple logistic regression analysis. RESULTS: A cutoff point in the number of pre-hospital defibrillation shocks most closely associated with 1-month OHCA survival was between two and three (χ(2) = 209.61, p < 0.0001). Among those patients who received two shocks or less, 34.48% survived for at least 1 month, compared with 24.75% of those who received three shocks or more. The number of defibrillations (odds ratio [OR] = 1.19, 95% CI: 1.03, 1.38), OHCA origin (OR = 2.81, 95% CI: 2.26, 3.49), use of ALS devices (OR = 0.68, 95% CI: 0.59, 0.79), use of epinephrine (OR = 0.33, 95% C: 0.28, 0.39), interval between first defibrillation and first ROSC (OR = 1.45, 95% CI: 1.18, 1.78), and chest compression (OR = 1.21, 95% CI: 1.06, 1.38) were associated significantly with 1-month OCHA survival. CONCLUSIONS: The cutoff point in the number of defibrillations of patients with OHCA most closely related to one-month survival was between 2 and 3, and the likelihood of non-survival 1 month after an OHCA was increased when ≥3 shocks were needed. Further studies are needed to verify this finding.

Favipiravir: a new medication for the Ebola virus disease pandemic.

The purpose of this report is to advocate speedy approval and less stringent regulations for the use of experimental drugs such as favipiravir in emergencies. Favipiravir is a new antiviral medication that can be used in emerging viral pandemics such as Ebola virus, 2009 pandemic influenza H1N1 virus, Lassa fever, and Argentine hemorrhagic fever. Although favipiravir is one of the choices for the treatment of patients with Ebola virus, several concerns exist. First, a clinical trial of favipiravir in patients infected with the Ebola virus has not yet been conducted, and further studies are required. Second, favipiravir has a risk for teratogenicity and embryotoxicity. Therefore, the Ministry of Health, Welfare and Labor of Japan has approved this medication with strict regulations for its production and clinical use. However, owing to the emerging Ebola virus epidemic in West Africa, on August 15, 2014, the Minister of Health, Welfare and Labor of Japan approved the use of favipiravir, if needed.

Factors associated with the clinical outcomes of paediatric out-of-hospital cardiac arrest in Japan.

OBJECTIVES: To better understand and predict clinical outcomes of paediatric out-of-hospital cardiac arrest (OHCA). DESIGN: A population-based, observational study. SETTING: The National Japan Utstein Registry. PARTICIPANTS: 2900 children aged 5-17 years who experienced OHCA and received resuscitation by emergency responders. Signal detection analysis using 17 variables was applied to identify factors associated with OHCA outcomes; the primary endpoint was cerebral performance category (CPC) 1 or 2. A validation study was conducted to verify the model. RESULTS: OHCA was identified as cardiac origin in 706 participants and non-cardiac origin in 2194 participants. Rates of CPC 1 or 2 for cardiac and non-cardiac causes were 20% and 6.4%, respectively. Cardiac origin arrest was categorised following signal detection into six subgroups defined by public automated external defibrillator use, defibrillation by emergency medical service, age, initial ECG rhythm and eye-witness to arrest; the ranges of CPC 1 or 2 in the six subgroups were between 87.5% and 0.7%. Non-cardiac origin arrest was categorised into four subgroups. Bystander rescue breathing was the most significant factor contributing to outcome; additionally, two other factors-eye-witness to arrest and age-were also significant. CPC 1 or 2 rates ranged between 38.5% and 4% across the four subgroups. Rates of CPC 1 or 2 in the validation study did not differ among any subgroup. CONCLUSIONS: For children who have OHCA from non-cardiac origin, bystander rescue breathing is mandatory to achieve CPC 1 or 2.

Rationale and study design of the Japan environment and children's study (JECS).

BACKGROUND: There is global concern over significant threats from a wide variety of environmental hazards to which children face. Large-scale and long-term birth cohort studies are needed for better environmental management based on sound science. The primary objective of the Japan Environment and Children's Study (JECS), a nation-wide birth cohort study that started its recruitment in January 2011, is to elucidate environmental factors that affect children's health and development. METHODS/DESIGN: Approximately 100,000 expecting mothers who live in designated study areas will be recruited over a 3-year period from January 2011. Participating children will be followed until they reach 13 years of age. Exposure to environmental factors will be assessed by chemical analyses of bio-specimens (blood, cord blood, urine, breast milk, and hair), household environment measurements, and computational simulations using monitoring data (e.g. ambient air quality monitoring) as well as questionnaires. JECS' priority outcomes include reproduction/pregnancy complications, congenital anomalies, neuropsychiatric disorders, immune system disorders, and metabolic/endocrine system disorders. Genetic factors, socioeconomic status, and lifestyle factors will also be examined as covariates and potential confounders. To maximize representativeness, we adopted provider-mediated community-based recruitment. DISCUSSION: Through JECS, chemical substances to which children are exposed during the fetal stage or early childhood will be identified. The JECS results will be translated to better risk assessment and management to provide healthy environment for next generations.

Physician presence in an ambulance car is associated with increased survival in out-of-hospital cardiac arrest: a prospective cohort analysis.

The presence of a physician seems to be beneficial for pre-hospital cardiopulmonary resuscitation (CPR) of patients with out-of-hospital cardiac arrest. However, the effectiveness of a physician's presence during CPR before hospital arrival has not been established. We conducted a prospective, non-randomized, observational study using national data from out-of-hospital cardiac arrests between 2005 and 2010 in Japan. We performed a propensity analysis and examined the association between a physician's presence during an ambulance car ride and short- and long-term survival from out-of-hospital cardiac arrest. Specifically, a full non-parsimonious logistic regression model was fitted with the physician presence in the ambulance as the dependent variable; the independent variables included all study variables except for endpoint variables plus dummy variables for the 47 prefectures in Japan (i.e., 46 variables). In total, 619,928 out-of-hospital cardiac arrest cases that met the inclusion criteria were analyzed. Among propensity-matched patients, a positive association was observed between a physician's presence during an ambulance car ride and return of spontaneous circulation (ROSC) before hospital arrival, 1-month survival, and 1-month survival with minimal neurological or physical impairment (ROSC: OR = 1.84, 95% CI 1.63-2.07, p = 0.00 in adjusted for propensity and all covariates); 1-month survival: OR = 1.29, 95% CI 1.04-1.61, p = 0.02 in adjusted for propensity and all covariates); cerebral performance category (1 or 2): OR = 1.54, 95% CI 1.03-2.29, p = 0.04 in adjusted for propensity and all covariates); and overall performance category (1 or 2): OR = 1.50, 95% CI 1.01-2.24, p = 0.05 in adjusted for propensity and all covariates). A prospective observational study using national data from out-of-hospital cardiac arrests shows that a physician's presence during an ambulance car ride was independently associated with increased short- and long-term survival.

Real-time NMR monitoring of protein-folding kinetics by a recycle flow system for temperature jump.

An NMR method was developed that allows for real-time monitoring of reactions (on the order of seconds) induced by a temperature jump. In a recycle flow system, heating and cooling baths were integrated, with the latter inside the NMR probe. A refolding reaction of ribonuclease A was triggered by rapid cooling and monitored by a series of NMR measurements over 12 s. Data were processed by principal component analysis, in which a factor related to the structural change with an exponential rate constant of 0.2-0.7 s(-1) was successfully separated from factors related to baseline instability and/or noise. Temperature dependency of the rate constant revealed the entropy-driven formation of the transition state of the refolding reaction.