Closed-loop acoustic stimulation during sedation with dexmedetomidine (CLASS-D): Protocol for a within-subject, crossover, controlled, interventional trial with healthy volunteers

Introduction: The relative power of slow-delta oscillations in the electroencephalogram (EEG), termed slow-wave activity (SWA), correlates with level of unconsciousness. Acoustic enhancement of SWA has been reported for sleep states, but it remains unknown if pharmacologically induced SWA can be enhanced using sound. Dexmedetomidine is a sedative whose EEG oscillations resemble those of natural sleep. This pilot study was designed to investigate whether SWA can be enhanced using closed-loop acoustic stimulation during sedation (CLASS) with dexmedetomidine. Methods: Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine (CLASS-D) is a within-subject, crossover, controlled, interventional trial with healthy volunteers. Each participant will be sedated with a dexmedetomidine target-controlled infusion (TCI). Participants will undergo three CLASS conditions in a multiple crossover design: in-phase (phase-locked to slow-wave upslopes), anti-phase (phase-locked to slow-wave downslopes) and sham (silence). High-density EEG recordings will assess the effects of CLASS across the scalp. A volitional behavioral task and sequential thermal arousals will assess the anesthetic effects of CLASS. Ambulatory sleep studies will be performed on nights immediately preceding and following the sedation session. EEG effects of CLASS will be assessed using linear mixed-effects models. The impacts of CLASS on behavior and arousal thresholds will be assessed using logistic regression modeling. Parametric modeling will determine differences in sleepiness and measures of sleep homeostasis before and after sedation. Results: The primary outcome of this pilot study is the effect of CLASS on EEG slow waves. Secondary outcomes include the effects of CLASS on the following: performance of a volitional task, arousal thresholds, and subsequent sleep. Discussion: This investigation will elucidate 1) the potential of exogenous sensory stimulation to potentiate SWA during sedation; 2) the physiologic significance of this intervention; and 3) the connection between EEG slow-waves observed during sleep and sedation

Exploring Learning Effectiveness for Participant Roles During Healthcare Simulation

Background: Universities face challenges in preparing future nurses for the workforce. It is essential to guide educators on strategies to achieve similar learning objectives to overcoming these challenges. Educators widely use the observer role in simulation, but researchers do not study the role thoroughly in current simulation research. There is a lack of discipline-specific research exploring how observers learn in simulation and if they can engage in the experiential learning intended in the simulation activity. Objectives: The objective of this research is to determine the difference in simulation effectiveness between the process-based role versus the response-based role (observers) in participants during simulation-based learning experiences. Design: This research used a quasi-experimental posttest only design to determine differences in simulation effectiveness among learner roles using the Simulation Effectiveness Tool-Modified (SET-M). Setting & participants: The researcher collected data from 193 prelicensure nursing students enrolled in any semester of one Midwestern undergraduate baccalaureate nursing program. Methods: Nursing students completed the assigned face-to-face simulations in their current curriculum plan. Each participant was randomly assigned to a participant role: direct participant role as either a primary or secondary nurse, non-directed observer with no briefing or observer guide, direct observer with an observation guide, or in- scenario observer assigned to a non-clinical or other professional role within the scenario. After debriefing of the simulation, participants completed the demographic survey and SET-M. Results: There were no significant differences found in prelicensure nursing students\u27 simulation effectiveness among the four participant roles studied. Conclusion: This study suggests simulation effectiveness (learning and confidence) happens regardless of the participants role during the simulation activity. Educators should consider what roles are necessary within each scenario and assign observation roles as needed

Impacts of Teacher–Child Managed Whole-Group Language and Literacy Instruction on the Depth of Preschoolers’ Social Interaction

Research Findings: This study examined the potential impacts of ongoing participation (twice weekly for 30 weeks) in teacher–child managed whole-group language and literacy instruction on prekindergarten children’s social interaction with classmates. Teacher–child managed whole-group instruction that provides children with opportunities to engage with all of their classmates regularly may potentially deepen the social depth within a classroom (i.e., the frequency with which children regularly interact with each other). Provision of this type of instruction occurred via teachers’ implementation of a whole-class literacy curriculum twice weekly. Participants were 119 preschoolers who received an experimental literacy curriculum in 26 classrooms and 76 children in 17 business-as-usual control classrooms. Condition predicted the strength of children’s social interaction, suggesting that children in experimental classrooms had relatively stronger social ties with peers than children in control classrooms. Practice or Policy: The findings suggest that participation in ongoing teacher–child managed whole-group instruction could facilitate stronger social connections among preschool children

Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial

BACKGROUND:Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis. METHODS:We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible. Patients were randomly assigned (1:1) via block randomisation using a random number generator to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. We analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02040298. FINDINGS:Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5-2·9; p=0·0048) when analysing the trial as a crossover. Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported. INTERPRETATION:To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage. FUNDING:University of California, San Francisco and the Rachleff Family