Efficacy and safety of modafinil in patients with idiopathic hypersomnia without long sleep time: a multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study.

BACKGROUND: Few treatments are available for patients with idiopathic hypersomnia (IH). Modafinil, an established treatment for narcolepsy, was tested for efficacy and safety in Japanese patients with IH without long sleep time. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study was conducted at 20 institutions in Japan. Patients who met the diagnostic criteria of IH in the International Classification of Sleep Disorders (second edition) were included. The study comprised a ≥17-day observation period and a 3-week treatment period during which modafinil (200 mg) or placebo was administered orally once daily (in the morning). The primary efficacy endpoint was change in mean sleep latency on the Maintenance of Wakefulness Test (MWT). Adverse events (AEs) were also recorded to evaluate safety. RESULTS: In total, 123 patients were screened and 71 were randomized to receive modafinil (N = 34) or placebo (N = 37). Patients treated with modafinil experienced a significantly prolonged mean sleep latency on the MWT at the end of the study compared with placebo (5.02 min, 95% confidence interval: 3.26-6.77 min; p < 0.001). AEs occurred in 58.8% (20/34) and 27.0% (10/37) of patients in the modafinil and placebo groups, respectively. Frequent AEs in the modafinil group were headache (n = 6), dry mouth (n = 3), and nausea (n = 3); no clinically significant AEs occurred. CONCLUSION: Modafinil was shown to be an effective and safe treatment for excessive daytime sleepiness in patients with IH without long sleep time. CLINICAL TRIAL REGISTRATION: JapicCTI; 142539.

Efficacy, safety, and pharmacokinetics of intravenous midazolam in Japanese children with status epilepticus.

BACKGROUND: No dosing regimen has been established for the initial treatment of pediatric status epilepticus with intravenous midazolam. We therefore evaluated the efficacy, safety, and pharmacokinetics of bolus and continuous midazolam infusion. METHODS: This open-label, prospective, multicenter study involved 34 Japanese children with status epilepticus unresponsive to diazepam. An initial bolus of 0.15 mg/kg midazolam was given, with additional doses of 0.1-0.3 mg/kg up to a cumulative dose of 0.6 mg/kg. A continuous infusion was initiated at 0.1 mg/kg/h (maximum 0.4 mg/kg/h) for patients at high risk of recurrence or in whom seizure reduction was achieved, and continued for 24 h after seizure cessation. Seizure cessation was assessed based on clinical observation (disappearance of motor symptoms regardless of recovery of consciousness), rather than the disappearance of electroencephalography abnormalities. RESULTS: The seizure cessation rate with bolus midazolam was 88%. The cumulative dose was ≤0.3 mg/kg in 90% of patients who responded to bolus administration. Adverse events were observed in three patients; one had mild respiratory depression that required supplemental oxygen and bag-valve-mask ventilation. Elimination half-life was 0.999 ±â€¯0.241 h in seven patients. Total body clearance ranged from 423 to 1220 mL/h/kg in older children but was notably higher in a 10-month-old infant (2010 mL/h/kg). CONCLUSIONS: The efficacy and safety of midazolam were demonstrated in children with status epilepticus, suggesting that intravenous midazolam is suitable as first-line treatment.

Ultrafast Generation of Unconventional {001} Loops in Si.

Ultrafast laser annealing of ion implanted Si has led to thermodynamically unexpected large {001} self-interstitial loops, and the failure of Ostwald ripening models for describing self-interstitial cluster growth. We have carried out molecular dynamics simulations in combination with focused experiments in order to demonstrate that at temperatures close to the melting point, self-interstitial rich Si is driven into dense liquidlike droplets that are highly mobile within the solid crystalline Si matrix. These liquid droplets grow by a coalescence mechanism and eventually transform into {001} loops through a liquid-to-solid phase transition in the nanosecond time scale.

Findings of the Maintenance of Wakefulness Test and its relationship with response to modafinil therapy for residual excessive daytime sleepiness in obstructive sleep apnea patients adequately treated with nasal continuous positive airway pressure.

OBJECTIVE: We aimed to examine the relationship between subjective and objective sleepiness in obstructive sleep apnea syndrome (OSAS) patients with residual sleepiness, and to determine whether baseline objective sleepiness severity predicts the response to modafinil therapy. METHODS: Data were obtained from a randomized, placebo-controlled modafinil (200 mg/day) study in Japanese OSAS patients with residual sleepiness receiving nasal continuous positive pressure (n-CPAP) treatment. We analyzed 50 participants whose subjective (Epworth Sleepiness Scale [ESS] total score) and objective (Maintenance of Wakefulness Test [MWT] sleep latency) sleepiness were evaluated before and after treatment. Subjects were dichotomized into two subgroups according to the mean baseline MWT sleep latency. ESS total score and MWT sleep latency changes after treatment were compared between the placebo and modafinil groups in both subgroups. RESULTS: The mean baseline ESS total score and MWT sleep latency were 14.1 ± 2.8 and 14.2 ± 4.9 min, respectively; there was no significant correlation between these two variables. Patient characteristics were similar between the two subgroups (MWT sleep latency: <14 min, n = 23; ≥14 min, n = 27). In the <14-min subgroup, changes in ESS total score and MWT sleep latency after treatment were significantly greater in the modafinil group than in the placebo group (p = 0.005). In the ≥14-min subgroup, changes in these parameters did not differ between the treatment groups. CONCLUSION: In OSAS patients with residual sleepiness, the objective sleepiness level was not as high as expected, despite increased subjective sleepiness. Improvements in subjective and objective sleepiness seemed difficult to achieve with modafinil treatment among subjects with less objective sleepiness.