Efficacy and safety of intravenous fosphenytoin for patients with acute herpes zoster-associated pain: A placebo-controlled randomized trial.

Acute zoster-associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster-associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster-associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double-blind, placebo-controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low-dose fosphenytoin group (n = 6, median age 62.5 years, range 39-75 years), high-dose fosphenytoin group (n = 5, median age 69.0 years, range 22-75 years), and placebo group (n = 5, median age 52.0 years, range 38-72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10-15 µg/mL. Treatment-emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster-associated pain. Trial Registration: ClinicalTrials.gov NCT04139330.

Effects of different visual presentation methods on movement procedure learning.

[Purpose] There is no established learning methods for movement procedures for activities of daily living. Patients with higher brain dysfunction and other disorders encounter challenges with movement procedures. Therefore, as a basic study on the memorization methods for movement procedures, we examined the differences between the effects of two memorization methods on healthy participants. [Participants and Methods] Forty student participants were asked to memorize and recall 10 movement elements. The control condition comprised all presented movements; whereas the intervention method comprised two movement elements (one block) each. The number of sets wherein all 10 movements were recalled and the number of consecutive recalls per set after 7 days were compared between the two conditions. [Results] The intervention method engendered significantly fewer sets that were recalled and significantly more consecutive recalls. [Conclusion] It is suggested that the method of presenting the movement procedure in smaller pieces is a more effective memory method than presenting the entire procedure.

Fosphenytoin Alleviates Herpes Simplex Virus Infection-Induced Provoked and Spontaneous Pain-Like Behaviors in Mice.

In this study, we investigated the effects of fosphenytoin (fPHT), a water-soluble prodrug of phenytoin, on the pain responses of a mouse herpes zoster (HZ) pain model. Transdermal herpes simplex virus type 1 (HSV-1) inoculation induced mechanical allodynia and hyperalgesia of the hind paw and spontaneous pain-like behaviors, such as licking the affected skin. Intravenous injection of fPHT (15 and 30 mg/kg) alleviated HSV-1-induced provoked pain (allodynia and hyperalgesia). The suppressive effects of fPHT on provoked pain were weaker than those of diclofenac and pregabalin which were used as positive controls. fPHT, diclofenac, and pregabalin significantly suppressed HSV-1-induced spontaneous pain-like behaviors. Among them, high-dose fPHT (30 mg/kg) showed the strongest suppression. Intravenous fPHT may become a viable option for an acute HZ pain, especially for spontaneous pain.

Validity and reliability of isometric knee extension muscle strength measurements using a belt-stabilized hand-held dynamometer: a comparison with the measurement using an isokinetic dynamometer in a sitting posture.

[Purpose] This study aimed to determine the validity and reliability of isometric knee extension muscle strength measurements using a belt-stabilized hand-held dynamometer compared to that using an isokinetic dynamometer with the participant in a sitting posture. [Participants and Methods] Forty-two university students participated. The isometric knee extension muscle strength was measured using a hand-held dynamometer and an isokinetic dynamometer. For both measurements, the participants were in the similar sitting posture. The sitting posture maintained trunk stability, with the hands on the bed, and the non-measurement-side toe touching the floor or table. The intra-class correlation coefficient and the relevance were verified. [Results] Intra-rater correlation coefficient (1, 1) of the two measurements was ≥0.75. A significant difference was found in the measurement value between males and females. No significant difference was found between the measurements value of the two devices. A significant positive correlation was found in the measurement value of two devices in the male participants. [Conclusion] When compared to the standard method of isometric knee extension muscle strength measurements using an isokinetic dynamometer with the participant in the sitting posture, measurements using the belt-stabilized hand-held dynamometer were considered valid and highly reliable in the male participants.