Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trial.

OBJECTIVE: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam (LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE. METHODS: We initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000-3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug. RESULTS: A total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061). CONCLUSION: The efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT. TRIAL REGISTRATION NUMBER: jRCTs031190160.

Impact of the COVID-19 pandemic on a trauma center of a university hospital in Japan.

BACKGROUND: The Coronavirus disease 2019 pandemic caused the Japanese government to declare a State of Emergency on April 7, 2020. The aim of this study is to provide an overview of the effects of the pandemic on surgical cases at a university hospital trauma center. METHODS: An observational study was performed at a trauma center in a tertiary hospital in Tokyo, Japan. The number of surgeries was compared between two periods: a historical control period (Tuesday April 9 to Monday May 27, 2019) and the period of the Japan State of Emergency due to COVID-19 (Tuesday April 7-Monday May 25, 2020). Information on patient age, gender, and surgical diagnosis, site, and procedure was collected for cases operated on in each period. The number of trauma surgeries was compared between the two periods. Data from the two periods were compared statistically. RESULTS: The total number of surgical cases was 151 in the control period and 83 in the COVID-19 period (including no cases with COVID-19), a decrease of 45.0%. There were significantly more surgeries for patients with hip fractures in the COVID-19 period (9 vs. 19, P < 0.001 by Fisher exact test). CONCLUSIONS: During the State of Emergency in Japan, the number of operations for trauma patients at the trauma center decreased, but surgeries for hip fracture increased.

Serum D-dimer level as a predictor of neurological functional prognosis in cases of head injuries caused by road traffic accidents.

BACKGROUND: The number of traffic fatalities is declining in Japan; however, a large proportion of head injuries are still attributable to traffic accidents. Severe head trauma may cause progressive and devastating coagulopathy owing to exacerbated coagulation and fibrinolysis, which results in massive bleeding and poor patient outcomes. D-dimer is a fibrinolytic marker, which remarkably increases in severe coagulopathy due to the exacerbated fibrinolytic system. Because the degree of coagulopathy is associated with patient outcomes, the D-dimer level is a useful prognostic predictor in patients with head trauma. However, the usefulness of D-dimer in cases of head trauma caused by road traffic accidents remains inadequately explored. In this study, we investigated the relationship between D-dimer levels and outcomes in head injuries caused by traffic accidents. METHODS: We extracted data on traffic injuries from Japan Neuro-Trauma Data Bank Project 2015, which is a prospective multicenter registry of head injuries. The analysis included 335 individuals with no missing data. The outcome variable was the score of the Glasgow Outcome Scale (GOS), a neurological outcome index. The participants were categorized into the favorable outcome (GOS score ≥ 4) and poor outcome (GOS score ≤ 3) groups. The serum D-dimer levels at the time of admission were divided into four categories at the quartiles, and the reference category was less than the first quartile (< 17.4 µg/mL). We performed a logistic regression analysis with GOS as the dependent variable and D-dimer as a predictor and performed a multivariate analysis that was adjusted for 10 physiological parameters. RESULTS: In the univariate analysis, all groups with serum D-dimer values ≥ 17.4 µg/dL showed significantly poorer outcomes than those of the reference group. In the multivariate analysis, after adjusting for other factors, D-dimer levels ≥ 89.3 µg/dL were an independent predictor of poor outcome. CONCLUSION: After adjusting for physiological parameters, high serum D-dimer levels can be an independent factor for predicting neurological prognosis in head trauma caused by road traffic accidents.

[Symptomatic seizure associated with takotsubo cardiomyopathy: a case report].

A 68-year-old woman was admitted for symptomatic seizure. She had a history of cerebral infarction in the right fronto-temporal lobes, and was medicated for the symptomatic seizure with valproic acid. Her electrocardiogram(EEG)showed ST-segment elevation in leads II, III, aVF, and V2-V6. Emergency coronary angiography showed normal coronary arteries, however, left ventriculography showed apical ballooning in the systolic phase. She had no chest pain or dyspnea, and takotsubo cardiomyopathy was diagnosed due to ECG abnormality. The majority of the takotusbo cardiomyopathy patients recover rapidly, but in some the condition proves fatal. Seizure-associated takotsubo cardiomyopathy may cause sudden unexplained death in epilepsy(SUDEP), and EEG measurements should be carefully checked for seizure patients.

Impact of physician-staffed ground emergency medical services-administered pre-hospital trauma care on in-hospital survival outcomes in Japan.

PURPOSE: In Japan, the vehicle used in pre-hospital trauma care systems with physician-staffed ground emergency medical services (GEMS) is referred to as a "doctor car". Doctor cars are highly mobile physician-staffed GEMS that can provide complex pre-hospital trauma management using various treatment strategies. The number of doctor car operations for patients with severe trauma has increased. Considering facility factors, the association between doctor cars and patient outcomes remains unclear. Therefore, this study aimed to examine the relationship between doctor cars for patients with severe trauma and survival outcomes in Japan. METHODS: A nationwide retrospective cohort study was conducted to compare the impact of the doctor car group with the non-physician-staffed GEMS group on in-hospital survival in adult patients with severe trauma. The data were analyzed using multivariable logistic regression models with generalized estimating equations. RESULTS: This study included 372,365 patients registered in the Japan Trauma Data Bank between April 2009 and March 2019. Of the 49,144 eligible patients, 2361 and 46,783 were classified into the doctor car and non-physician staffed GEMS groups, respectively. The adjusted odds ratio (OR) for survival was significantly higher in the doctor car group than in the non-physician staffed GEMS group (adjusted OR = 1.228 [95% confidence interval 1.065-1.415]). CONCLUSION: Using nationwide data, this novel study suggests that doctor cars improve the in-hospital survival rate of patients with severe trauma in Japan. Therefore, doctor cars could be an option for trauma strategies.

Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial.

BACKGROUND: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE. METHODS: This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is "continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance." In both groups, diazepam is initially administered at 1-20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000-3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes. DISCUSSION: The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019.