4), showed a statistically significant drop of 10.3 points (−13.7 to −6.9; P < 0.0001). Standard effect size (Cohen's d) was 2.68 for change in ISI. Figure 4 Baseline and post-HIRREM Insomnia Severity Index (ISI) scores for usual care (UC) and HIRREM plus usual care (HUC) groups. see more Differential change: −10.3 (95% CI: −13.7 to −6.9), P < 0.0001. Secondary outcomes The UC group was then offered crossover to receive HIRREM. There was no statistical difference for analysis of differential change Inhibitors,research,lifescience,medical in the ISI following

HIRREM intervention between the HUC group and the crossover UC group. The ISI was also administered at a telephone follow-up at least 4 weeks following completion of the HIRREM intervention. The improvement in insomnia symptoms reported following completion of the HIRREM sessions persisted through that period (Fig. 5). Figure 5 Baseline to post-HIRREM changes in Insomnia Inhibitors,research,lifescience,medical Severity Index (ISI) scores for usual care (UC) and HIRREM

plus usual care (HUC) groups after cross-over, with 4- to 6-week late follow-up ISI scores. Considering clinical threshold correlates for insomnia, based on the differential change in mean ISI, the HUC group improved to just under the cut point for Inhibitors,research,lifescience,medical subthreshold insomnia category, while the UC group remained in the moderate insomnia category (Table 3). As a way to consider clinically relevant changes for individual subjects, the number of subjects in each category,

before and after each study epoch, shows that 9/10 in the UC group remained in the moderate-to-severe Inhibitors,research,lifescience,medical insomnia category, while 9/10 in the HUC group moved to the no insomnia or subthreshold categories following HIRREM. Following crossover and receipt of HIRREM, 6/9 in the UC group also improved to no insomnia or subthreshold insomnia, and the effects persisted with late follow-up after HIRREM for both groups. Table 3 Changes in clinical category for insomnia after Inhibitors,research,lifescience,medical HIRREM based on ISI scores Differential change in the CES-D score during the primary intervention period reached statistical significance with a drop of 8.8 points (−17.5 to −0.1; P = 0.047). Differential change was not statistically significant for the total SF-36 score, which increased by 4.0 (−6.8 to 14.8; P = 0.446), but there were small effect sizes for some components of the SF-36, with effect size values ranging Phosphatidylinositol diacylglycerol-lyase from 0.07 for physical function to 0.58 for energy and fatigue. There were also no statistically significant changes for the neurocognitive measures, although several domains, psychomotor speed (0.38), neurocognitive index (0.24), and complex attention (0.22) showed small effect sizes. Due to the small sample size, there was inadequate power for analysis of other secondary and exploratory outcome measures. Poor technical quality of recordings precluded analysis of HRV measures.