The effects of ketamine on symptoms of depression and anxiety in real-world care settings: A retrospective controlled analysis.

INTRODUCTION: Ketamine intravenous therapy (KIT) appears effective for treating depression in controlled trials testing a short series of infusions. A rapidly proliferating number of clinics offer KIT for depression and anxiety, using protocols without a strong evidence basis. Controlled comparison of mood and anxiety from real-world KIT clinics, and the stability of outcomes, is lacking. METHODS: We performed a retrospective controlled analysis on patients treated with KIT in ten community clinics across the US, between 08/2017-03/2020. Depression and anxiety symptoms were evaluated using the Quick Inventory of Depressive Symptomatology-Self Report 16-item (QIDS) and the Generalized Anxiety Disorder 7-item (GAD-7) scales, respectively. Comparison data sets from patients who did not undergo KIT were obtained from previously published real-world studies. RESULTS: Of 2758 patients treated, 714 and 836 met criteria for analysis of KIT induction and maintenance outcomes, respectively. Patients exhibited significant and concordant reduction in both anxiety and depression symptoms after induction (Cohen's d = -1.17 and d = -1.56, respectively). Compared to two external datasets of KIT-naive depressed patients or patients starting standard antidepressant therapy, KIT patients experienced a significantly greater reduction in depression symptoms at eight weeks (Cohen's d = -1.03 and d = -0.62 respectively). Furthermore, we identified a subpopulation of late-responders. During maintenance, up to a year post-induction, increases in symptoms were minimal. LIMITATIONS: Due to the retrospective nature of the analyses, interpreting this dataset is limited by incomplete patient information and sample attrition. CONCLUSIONS: KIT treatment elicited robust symptomatic relief that remained stable up to one year of follow-up.

Assessing Pediatric Life Support Skills Using Augmented Reality Medical Simulation With Eye Tracking: A Pilot Study.

Background: Augmented reality (AR) and eye tracking are promising adjuncts for medical simulation, but they have remained distinct tools. The recently developed Chariot Augmented Reality Medical (CHARM) Simulator combines AR medical simulation with eye tracking. We present a novel approach to applying eye tracking within an AR simulation to assess anesthesiologists during an AR pediatric life support simulation. The primary aim was to explore clinician performance in the simulation. Secondary outcomes explored eye tracking as a measure of shockable rhythm recognition and participant satisfaction. Methods: Anesthesiology residents, pediatric anesthesiology fellows, and attending pediatric anesthesiologists were recruited. Using CHARM, they participated in a pediatric crisis simulation. Performance was scored using the Anesthesia-centric Pediatric Advanced Life Support (A-PALS) scoring instrument, and eye tracking data were analyzed. The Simulation Design Scale measured participant satisfaction. Results: Nine each of residents, fellows, and attendings participated for a total of 27. We were able to successfully progress participants through the AR simulation as demonstrated by typical A-PALS performance scores. We observed no differences in performance across training levels. Eye tracking data successfully allowed comparisons of time to rhythm recognition across training levels, revealing no differences. Finally, simulation satisfaction was high across all participants. Conclusions: While the agreement between A-PALS score and gaze patterns is promising, further research is needed to fully demonstrate the use of AR eye tracking for medical training and assessment. Physicians of multiple training levels were satisfied with the technology.

Communication Skills Training Using Remote Augmented Reality Medical Simulation: a Feasibility and Acceptability Qualitative Study.

Introduction: Augmented reality (AR) has promise as a clinical teaching tool, particularly for remote learning. The Chariot Augmented Reality Medical (CHARM) simulator integrates real-time communication into a portable medical simulator with a holographic patient and monitor. The primary aim was to analyze feedback from medical and physician assistant students regarding acceptability and feasibility of the simulator. Methods: Using the CHARM simulator, we created an advanced cardiovascular life support (ACLS) simulation scenario. After IRB approval, preclinical medical and physician assistant students volunteered to participate from August to September 2020. We delivered augmented reality headsets (Magic Leap One) to students before the study. Prior to the simulation, via video conference, we introduced students to effective communication skills during a cardiac arrest. Participants then, individually and remotely from their homes, synchronously completed an instructor-led ACLS AR simulation in groups of three. After the simulation, students participated in a structured focus group using a qualitative interview guide. Our study team coded their responses and interpreted them using team-based thematic analysis. Results: Eighteen medical and physician assistant students participated. We identified four domains that reflected trainee experiences: experiential satisfaction, learning engagement, technology learning curve, and opportunities for improvement. Students reported that the simulator was acceptable and enjoyable for teaching trainees communication skills; however, there were some technical difficulties associated with initial use. Conclusion: This study suggests that multiplayer AR is a promising and feasible approach for remote medical education of communication skills during medical crises. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01598-7.

A retrospective analysis of ketamine intravenous therapy for depression in real-world care settings.

BACKGROUND: Outcomes of ketamine intravenous therapy (KIT) for depression in real-world care settings have been minimally evaluated. We set out to quantify treatment response to KIT in a large sample of patients from community-based practices. METHODS: We retrospectively analyzed 9016 depression patients who received KIT between 2016 and 2020 at one of 178 community practices across the United States. Depression symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). The induction phase of KIT was defined to be a series of 4-8 infusions administered over 7 to 28 days. RESULTS: Among the 537 patients who underwent induction and had sufficient data, 53.6% of patients showed a response (≥ 50% reduction in PHQ-9 score) at 14-31 days post-induction and 28.9% remitted (PHQ-9 score drop to < 5). The effect size was d = 1.5. Among patients with baseline suicidal ideation (SI), 73.0% exhibited a reduction in SI. A subset (8.4%) of patients experienced an increase in depressive symptoms after induction while 6.0% of patients reported increased SI. The response rate was uniform across 4 levels of baseline depression severity. However, more severe illness was weakly correlated with a greater drop in scores while remission status was weakly inversely correlated with depression severity. Kaplan-Meier analyses showed that a patient who responds to KIT induction has approximately 80% probability of sustaining response at 4 weeks and approximately 60% probability at 8 weeks, even without maintenance infusions. CONCLUSION: KIT can elicit a robust antidepressant response in community clinics; however, a small percentage of patients worsened.

Development and assessment of an efficient pediatric affect and cooperation scale.

STUDY OBJECTIVE: HRAD± was developed to quickly evaluate pediatric preprocedural affect and cooperativity during mask induction of anesthesia and peripheral intravenous (PIV) placement. HRAD± represents: Happy, Relaxed, Anxious, Distressed, with a yes/no answer to cooperativity. The primary aim of this study was to compare HRAD± to previously published scales. DESIGN: We conducted an observational study. SETTING: Videos of pediatric patients were collected in the perioperative environment. PATIENTS: Twenty-four children, twenty-one pediatric anesthesiologists and twenty pediatric perioperative providers were included. INTERVENTIONS: To assess the reliability of HRAD±, standard patient videos were created. Children underwent mask induction or PIV placement, and these interventions were video recorded. Mask induction and PIV placement videos were rated by pediatric anesthesiologists and perioperative non-physician providers respectively using HRAD±. MEASUREMENTS: Two trained researchers provided the modified Yale Preoperative Anxiety Scale (mYPAS), Observation Scale of Behavioral Distress (OSBD), and Induction Compliance Checklist (ICC) scores, and we calculated correlations to HRAD±, inter-rater reliability, and intra-rater reliability. MAIN RESULTS: HRAD± scores strongly correlated with mYPAS (r = 0.846, p < 0.0001) and OSBD scores (r = 0.723, p < 0.0001). Cooperativity scores correlated strongly with ICC scores in the mask induction group (r = -0.715, p < 0.0001) and in the PIV group (r = -0.869, p < 0.0001). HRAD± inter-rater reliability for mask induction was 0.414 (p < 0.0001) and for PIV assessment was 0.378 (p < 0.0001). Inter-rater reliability for cooperativity on mask induction was 0.797 (p < 0.0001) and PIV assessment was 0.683 (p < 0.0001). Intra-rater reliability for mask induction was 0.675 and PIV assessments was 0.678. Intra-rater reliability for cooperativity for mask induction was 0.894 and for PIV assessments was 0.765. CONCLUSIONS: HRAD± is an efficient and reliable scale that serves as a practical alternative for measuring pediatric affect during mask induction and PIV placement. The results demonstrate strong correlation with commonly utilized yet more complex affect scales.

From Socrates to Virtual Reality: A Historical Review of Learning Theories and Their Influence on the Training of Anesthesiologists.

Over the past couple of centuries, the training of American physicians, and anesthesiologists in particular, has undergone a radical transformation. The revolution of medical training has been and continues to be fueled by insights from learning theorists. In this historical review, we discuss the origins of American medical education in the 1700s and continue through the centuries illustrating the impact of learning theories on the education and training of anesthesiologists. In particular, we explore the impact of learning theories of the 1800s and the adult-centered teaching strategies of the 1900s. We also discuss the role of learning theories in molding medical education in the modern technological age.

Retrospective Review of the Safety and Efficacy of Virtual Reality in a Pediatric Hospital.

INTRODUCTION: Virtual reality (VR) is an emerging tool for anxiety and fear reduction in pediatric patients. VR use is facilitated by Certified Child Life Specialists (CCLS) at pediatric hospitals. The primary aim of this study was to retrospectively review the safety of VR by analyzing adverse events after the utilization of VR under CCLS supervision. Secondary objectives were to characterize the efficacy of VR in enhancing patient cooperation, describe the integration of VR into Child Life services, and identify interventions that accompanied VR. METHODS: The Stanford Chariot Program developed VR applications, customized VR interfaces, and patient head straps, and distributed these to CCLS. Chart review analyzed VR utilization through CCLS patient notes. Inclusion criteria were all patients ages 6 to 18-years-old who received a Child Life intervention. RESULTS: From June 2017 to July 2018, 31 CCLS saw 8,098 patients, 3,696 of which met age criteria with pre- and post-intervention cooperation data. Two hundred thirteen patients received VR with an accompanying intervention, while 34 patients received only VR. Adverse events were rare, and included increased anxiety (3.8%, n=8), dizziness (0.5%, n=1), and nausea (0.5%, n=1). Patients were more likely to be cooperative after receiving VR (99.5%, n=212) compared to pre-intervention (96.7%, n=206, p=0.041). VR use was most common in the perioperative setting (60%, n=128), followed by outpatient clinics (15%, n=32). CONCLUSION: VR is safe in pediatric patients with appropriate hardware, software, and patient selection. Side effects were rare and self-limited. VR appears to be associated with improvements in cooperation.

The balance of interaction types determines the assembly and stability of ecological communities.

What determines the assembly and stability of complex communities is a central question in ecology. Past work has suggested that mutualistic interactions are inherently destabilizing. However, this conclusion relies on the assumption that benefits from mutualisms never stop increasing. Furthermore, almost all theoretical work focuses on the internal (asymptotic) stability of communities assembled all at once. Here, we present a model with saturating benefits from mutualisms and sequentially assembled communities. We show that such communities are internally stable for any level of diversity and any combination of species interaction types. External stability, or resistance to invasion, is thus an important but overlooked measure of stability. We demonstrate that the balance of different interaction types governs community dynamics. A higher fraction of mutualistic interactions can increase the external stability and diversity of communities as well as species persistence, if mutualistic interactions tend to provide unique benefits. Ecological selection increases the prevalence of mutualisms, and limits on biodiversity emerge from species interactions. Our results help resolve long-standing debates on the stability, saturation and diversity of communities.

Competition and niche construction in a model of cancer metastasis.

Niche construction theory states that not only does the environment act on populations to generate Darwinian selection, but organisms reciprocally modify the environment and the sources of natural selection. Cancer cells participate in niche construction as they alter their microenvironments and create pre-metastatic niches; in fact, metastasis is a product of niche construction. Here, we present a mathematical model of niche construction and metastasis. Our model contains producers, which pay a cost to contribute to niche construction that benefits all tumor cells, and cheaters, which reap the benefits without paying the cost. We derive expressions for the conditions necessary for metastasis, showing that the establishment of a mutant lineage that promotes metastasis depends on niche construction specificity and strength of interclonal competition. We identify a tension between the arrival and invasion of metastasis-promoting mutants, where tumors composed only of cheaters remain small but are susceptible to invasion whereas larger tumors containing producers may be unable to facilitate metastasis depending on the level of niche construction specificity. Our results indicate that even if metastatic subclones arise through mutation, metastasis may be hindered by interclonal competition, providing a potential explanation for recent surprising findings that most metastases are derived from early mutants in primary tumors.