Efficacy and safety of on-demand use of 2 treatments designed for different etiologies of female sexual interest/arousal disorder:3 Randomized Clinical Trials

Background In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. Aim To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. Methods 497 women (21–70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). Outcomes The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. Results In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57–2.84, P =.004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44–3.45, P =.012; T: Δ = 1.69, 95% CI = 0.58–2.80, P =.003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17–1.82, P =.019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57–2.46, P =.002; T: Δ = 0.98, 95% CI = 0.17–1.78, P =.018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). Clinical Implications T + S and T + B are promising treatments for women with FSIAD. Strengths and Limitations The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. Conclusions T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201–216

Temporal stability of the Launay-Slade Hallucination Scale for high- and low-scoring normal subjects

It has been documented that many normal people report hallucinatory experiences. The Launay-Slade Hallucination Scale is widely used to investigate differences between subjects who score high or low in hallucinatory predisposition. In this study we addressed the question of whether scores remain stable over time. We selected 19 high-scoring subjects and 17 low-scoring subjects (upper and lower quartile) from a group of 243 undergraduate students who completed the scale. These two groups retook the scale after a period of 3 to 6 weeks. 81% received the same classification, which supports the view of hallucinatory predisposition as a stable trait; however, for 30% of the subjects the mean rating at the second time differed more than 3 SDs from the mean rating at the first time. In addition, the mean rating of 19% of subjects changed enough so they did not receive the same classification, indicating that state characteristics may also affect these scores

Stochastic maximum likelihood mean and cross-spectrum structure modelling in neuro-magnetic source estimation

In [R.P.P.P. Grasman et al., Frequency domain simultaneous source and source coherence estimation with an application to MEG, IEEE Trans. Biomed. Eng. 51 (1) (2004) 45–55] we proposed to analyze cross-spectrum matrices obtained from electro- or magnetoencephalographic (EEG/MEG) signals, to obtain estimates of the EEG/MEG sources and their coherence. In this paper we extend this method in two ways. First, by modelling such interactions as linear filters, and second, by taking the mean of the signals across different trials into account. To obtain estimates we propose a stochastic maximum likelihood (SML) method, and obtain the concentrated likelihood that includes the trial\ud means

Event-related desynchronization related to the anticipation of a stimulus providing knowledge of results

In the present paper, event-related desynchronization (ERD) in the alpha and beta frequency bands is quantified in order to investigate the processes related to the anticipation of a knowledge of results (KR) stimulus. In a time estimation task, 10 subjects were instructed to press a button 4 s after the presentation of an auditory stimulus. Two seconds after the response they received auditory or visual feedback on the timing of their response. Preceding the button press, a centrally maximal ERD is found. Preceding the visual KR stimulus, an ERD is present that has an occipital maximum. Contrary to expectation, preceding the auditory KR stimulus there are no signs of a modalityspecific ERD. Results are related to a thalamo-cortical gating model which predicts a correspondence between negative slow potentials and ERD during motor preparation and stimulus anticipation