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Onychomycosis with longitudinal spikes in the nail plate has been reported to be refractory to oral drugs as with dermatophytoma. We evaluated the efficacy of 10% efinaconazole solution in the treatment of onychomycosis with longitudinal spikes. Of the 223 subjects who were enrolled in a previous study, a post-hoc analysis of 82 subjects with longitudinal spikes was performed in this study. The opacity ratio of longitudinal spikes was decreased over time from 8.1 to 0.9 at the final assessment. In addition, the longitudinal spike disappearance rate increased early after the application to 81.7% at the final assessment. Therefore, 10% efinaconazole solution can be a first-line drug for longitudinal spikes, which have been regarded as refractory to oral drugs., (© 2021 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

The "Guidelines for the management of dermatomycosis" of the Japanese Dermatological Association were first published in Japanese in 2009 and the Guidelines Committee of the Japanese Dermatological Association revised it in 2019. The first guidelines was prepared according to the opinions of the Guidelines Committee members and it was of educational value. The revised version is composed of introductory descriptions of the disease concepts, diagnosis, medical mycology and recent advances in treatment, along with clinical questions (CQ), which is intended to help in general practice for dermatologists. The CQ are limited to those involved in therapy but include some of the recently launched antifungal agents. The level of evidence and the degree of recommendation for each item were reviewed by the committee based on clinical studies published by 2018. For rare dermatomycoses, recommendations by the committee are described in the guidelines. In this field, there are still few good quality studies on treatment. Periodic revision in line with new evidence is necessary., (© 2020 Japanese Dermatological Association.)

We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis., (© 2019 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

We determined the effect of cocaine on ventricular vulnerability to fibrillation, as measured by ventricular fibrillation threshold (VFT), and cardiac electrophysiology in 20 anesthetized dogs with normal hearts. Animals were randomized in blinded fashion to receive a continuous 3-hour infusion of cocaine 0.11 mg/kg/minute (total dose 20 mg/kg) or placebo (lactose dissolved in normal saline). The VFT, systolic and diastolic blood pressures, ventricular effective refractory period (ERP), and electrocardiographic intervals were measured at baseline and every 30 minutes during infusion. Baseline mean +/- SE VFT in cocaine and placebo groups was 57.0 +/- 7.8 and 51.8 +/- 7.6 mA, respectively (p = 0.64). Cocaine did not significantly decrease VFT, but actually increased it (i.e., reduced ventricular vulnerability to fibrillation) compared with placebo (84.6 +/- 10.4 vs 55.8 +/- 7.2 mA, respectively, at 150 minutes, p = 0.04). Cocaine prolonged ERP and PR, QRS, QT, QTc, JT, and JTc intervals. Cocaine does not increase ventricular vulnerability to fibrillation in anesthetized dogs with normal intact hearts. Its electrophysiologic effects are similar to those of class I antiarrhythmic agents in this model.

To determine and describe relationships between plasma cocaine concentrations and electrophysiologic and electrocardiographic effects, 10 anesthetized dogs with normal intact hearts received a continuous 3-hour infusion of cocaine 0.11 mg/kg/minute (total dose 20 mg/kg). Data were collected as part of a randomized, blinded, placebo-controlled study investigating the effects of cocaine on ventricular fibrillation threshold. Every 30 minutes during infusion of cocaine or placebo and for 3 hours after discontinuation of the infusion, heart rate and mean arterial pressure were determined, effective refractory period (ERP) was measured, and QRS duration and PR, QTc, and JTc intervals were recorded. At the time of each 30-minute measurement, arterial blood was obtained to determine plasma cocaine concentrations. Hysteresis curves were observed for cocaine-induced increases in ERP and PR interval. The effects of cocaine on QRS duration and QTc and JTc intervals were not well described by tested models. Pharmacodynamic modeling techniques may be used to describe relationships between plasma cocaine concentrations and specific cardiovascular effects of cocaine. Further study is required to determine applicability of this model for prediction of cocaine's cardiovascular effects in humans.