Medical Students\u27 Experiences and Outcomes Using a Virtual Human Simulation to Improve Communication Skills: Mixed Methods Study

Background: Attending to the wide range of communication behaviors that convey empathy is an important but often underemphasized concept to reduce errors in care, improve patient satisfaction, and improve cancer patient outcomes. A virtual human (VH)–based simulation, MPathic-VR, was developed to train health care providers in empathic communication with patients and in interprofessional settings and evaluated through a randomized controlled trial. Objective: This mixed methods study aimed to investigate the differential effects of a VH-based simulation developed to train health care providers in empathic patient-provider and interprofessional communication. Methods: We employed a mixed methods intervention design, involving a comparison of 2 quantitative measures—MPathic-VR–calculated scores and the objective structured clinical exam (OSCE) scores—with qualitative reflections by medical students about their experiences. This paper is a secondary, focused analysis of intervention arm data from the larger trial. Students at 3 medical schools in the United States (n=206) received simulation to improve empathic communication skills. We conducted analysis of variance, thematic text analysis, and merging mixed methods analysis. Results: OSCE scores were significantly improved for learners in the intervention group (mean 0.806, SD 0.201) compared with the control group (mean 0.752, SD 0.198; F1,414=6.09; P=.01). Qualitative analysis revealed 3 major positive themes for the MPathic-VR group learners: gaining useful communication skills, learning awareness of nonverbal skills in addition to verbal skills, and feeling motivated to learn more about communication. Finally, the results of the mixed methods analysis indicated that most of the variation between high, middle, and lower performers was noted about nonverbal behaviors. Medium and high OSCE scorers most often commented on the importance of nonverbal communication. Themes of motivation to learn about communication were only present in middle and high scorers. Conclusions: VHs are a promising strategy for improving empathic communication in health care. Higher performers seemed most engaged to learn, particularly nonverbal skills

Somatostatin-expressing parafacial neurons are CO2/H+ sensitive and regulate baseline breathing.

Glutamatergic neurons in the retrotrapezoid nucleus (RTN) function as respiratory chemoreceptors by regulating breathing in response to tissue CO2/H+. The RTN and greater parafacial region may also function as a chemosensing network composed of CO2/H+-sensitive excitatory and inhibitory synaptic interactions. In the context of disease, we showed that loss of inhibitory neural activity in a mouse model of Dravet syndrome disinhibited RTN chemoreceptors and destabilized breathing (Kuo et al., 2019). Despite this, contributions of parafacial inhibitory neurons to control of breathing are unknown, and synaptic properties of RTN neurons have not been characterized. Here, we show the parafacial region contains a limited diversity of inhibitory neurons including somatostatin (Sst)-, parvalbumin (Pvalb)-, and cholecystokinin (Cck)-expressing neurons. Of these, Sst-expressing interneurons appear uniquely inhibited by CO2/H+. We also show RTN chemoreceptors receive inhibitory input that is withdrawn in a CO2/H+-dependent manner, and chemogenetic suppression of Sst+ parafacial neurons, but not Pvalb+ or Cck+ neurons, increases baseline breathing. These results suggest Sst-expressing parafacial neurons contribute to RTN chemoreception and respiratory activity

Initial Construct Validity Evidence of a Virtual Human Application for Competency Assessment in Breaking Bad News to a Cancer Patient

Background: Despite interest in using virtual humans (VHs) for assessing health care communication, evidence of validity is limited. We evaluated the validity of a VH application, MPathic-VR, for assessing performance-based competence in breaking bad news (BBN) to a VH patient. Methods: We used a two-group quasi-experimental design, with residents participating in a 3-hour seminar on BBN. Group A (n=15) completed the VH simulation before and after the seminar, and Group B (n=12) completed the VH simulation only after the BBN seminar to avoid the possibility that testing alone affected performance. Pre-and postseminar differences for Group A were analyzed with a paired t-test, and comparisons between Groups A and B were analyzed with an independent t-test. Results: Compared to the preseminar result, Group A\u27s postseminar scores improved significantly, indicating that the VH program was sensitive to differences in assessing performance-based competence in BBN. Postseminar scores of Group A and Group B were not significantly different, indicating that both groups performed similarly on the VH program. Conclusion: Improved pre-post scores demonstrate acquisition of skills in BBN to a VH patient. Pretest sensitization did not appear to influence posttest assessment. These results provide initial construct validity evidence that the VH program is effective for assessing BBN performance-based communication competence

Reducing Symptom Distress in Patients with Advanced Cancer Using an e-Alert System for Caregivers: Pooled Analysis of Two Randomized Clinical Trials

Background: Symptom distress in patients toward the end of life can change rapidly. Family caregivers have the potential to help patients manage those symptoms, as well as their own stress, if they are equipped with the proper resources. Electronic health (eHealth) systems may be able to provide those resources. Very sick patients may not be able to use such systems themselves to report their symptoms but family caregivers could. Objective: The aim of this paper was to assess the effects on cancer patient symptom distress of an eHealth system that alerts clinicians to significant changes in the patient’s symptoms, as reported by a family caregiver. Methods: A pooled analysis from two randomized clinical trials (NCT00214162 and NCT00365963) compared outcomes at 12 months for two unblinded groups: a control group (Comprehensive Health Enhancement Support System [CHESS]-Only) that gave caregivers access to CHESS, an online support system, and an experimental group (CHESS+CR [Clinician Report]), which also had CHESS but with a CR that automatically alerted clinicians if symptoms exceeded a predetermined threshold of severity. Participants were dyads (n=235) of patients with advanced lung, breast, or prostate cancer and their respective family caregivers from 5 oncology clinics in the United States of America. The proportion of improved patient threshold symptoms was compared between groups using area-under-the-curve analysis and binomial proportion tests. The proportion of threshold symptoms out of all reported symptoms was also examined. Results: When severe caregiver-reported symptoms were shared with clinicians, the symptoms were more likely to be subsequently reported as improved than when the symptoms were not shared with clinicians (P \u3c .001). Fewer symptom reports were completed in the group of caregivers whose reports went to clinicians than in the CHESS-Only group (P \u3c .001), perhaps because caregivers, knowing their reports might be sent to a doctor, feared they might be bothering the clinician. Conclusions: This study suggests that an eHealth system designed for caregivers that alerts clinicians to worrisome changes in patient health status may lead to reduced patient distress. Trial Registration: Clinicaltrials.gov NCT00214162; https://clinicaltrials.gov/ct2/show/NCT00214162 (Archived by WebCite at http://www.webcitation.org/6nmgdGfuD) and Clinicaltrials.gov NCT00365963; https://clinicaltrials.gov/ct2/show/NCT00365963 (Archived by WebCite at http://www.webcitation.org/6nmh0U8VP

Angular position of nodes in the superconducting gap of YBCO

The thermal conductivity of a YBCO single crystal has been studied as a function of the relative orientation of the crystal axes and a magnetic field rotating in the Cu-O planes. Measurements were carried out at several temperatures below T_c and at a fixed field of 30 kOe. A four-fold symmetry characteristic of a superconducting gap with nodes at odd multiples of 45 degrees in k-space was resolved. Experiments were performed to exclude a possible macroscopic origin for such a four-fold symmetry such as sample shape or anisotropic pinning. Our results impose an upper limit of 10% on the weight of the s-wave component of the essentially d-wave superconducting order parameter of YBCO.Comment: 10 pages, 4 figure

CHESS Improves Cancer Caregivers\u27 Burden and Mood: Results of an eHealth RCT

OBJECTIVE: Informal caregivers (family and friends) of people with cancer are often unprepared for their caregiving role, leading to increased burden or distress. Comprehensive Health Enhancement Support System (CHESS) is a Web-based lung cancer information, communication, and coaching system for caregivers. This randomized trial reports the impact on caregiver burden, disruptiveness, and mood of providing caregivers access to CHESS versus the Internet with a list of recommended lung cancer websites. METHODS: A total of 285 informal caregivers of patients with advanced nonsmall cell lung cancer were randomly assigned to a comparison group that received Internet or a treatment group that received Internet and CHESS. Caregivers were provided a computer and Internet service if needed. Written surveys were completed at pretest and during the intervention period bimonthly for up to 24 months. Analyses of covariance (ANCOVAs) compared the intervention\u27s effect on caregivers\u27 disruptiveness and burden (CQOLI-C), and negative mood (combined Anxiety, Depression, and Anger scales of the POMS) at 6 months, controlling for blocking variables (site, caregiver\u27s race, and relationship to patient) and the given outcome at pretest. RESULTS: Caregivers randomized to CHESS reported lower burden, t(84) = 2.36, p = .021, d = .39, and negative mood, t(86) = 2.82, p = .006, d = .44, than those in the Internet group. The effect on disruptiveness was not significant. CONCLUSIONS: Although caring for someone with a terminal illness will always exact a toll on caregivers, eHealth interventions like CHESS may improve caregivers\u27 understanding and coping skills and, as a result, ease their burden and mood

An eHealth System Supporting Palliative Care for Patients with Non-Small Cell Lung Cancer: A Randomized Trial

BACKGROUND: In this study, the authors examined the effectiveness of an online support system (Comprehensive Health Enhancement Support System [CHESS]) versus the Internet in relieving physical symptom distress in patients with non-small cell lung cancer (NSCLC). METHODS: In total, 285 informal caregiver-patient dyads were assigned randomly to receive, for up to 25 months, standard care plus training on and access to either use of the Internet and a list of Internet sites about lung cancer (the Internet arm) or CHESS (the CHESS arm). Caregivers agreed to use CHESS or the Internet and to complete bimonthly surveys; for patients, these tasks were optional. The primary endpoint-patient symptom distress-was measured by caregiver reports using a modified Edmonton Symptom Assessment Scale. RESULTS: Caregivers in the CHESS arm consistently reported lower patient physical symptom distress than caregivers in the Internet arm. Significant differences were observed at 4 months (P = .031; Cohen d = .42) and at 6 months (P = .004; d = .61). Similar but marginally significant effects were observed at 2 months (P = .051; d = .39) and at 8 months (P = .061; d = .43). Exploratory analyses indicated that survival curves did not differ significantly between the arms (log-rank P = .172), although a survival difference in an exploratory subgroup analysis suggested an avenue for further study. CONCLUSIONS: The current results indicated that an online support system may reduce patient symptom distress. The effect on survival bears further investigation

Tacrolimus does not abrogate the increased risk of acute graft-versus-host disease after unrelated-donor marrow transplantation with allelic mismatching at HLA-DRB1 and HLA-DQB1

AbstractOne hundred patients of median age 34 years (range, 14-53) received bone marrow transplants from unrelated donors serologically matched for human leukocyte antigen HLA-A, HLA-B, and HLA-DR using tacrolimus and minimethotrexate for prevention of acute graft-versus-host disease (GVHD). Sixty-eight patient-donor pairs had allelic matches at HLA-DRB1 and HLA-DQB1, 20 pairs had a single mismatch at HLA-DRB1 or HLA-DQB1, and 12 were mismatched at both HLA-DRB1 and HLA-DQB1. Minimum follow-up time was 6 months. Grades 2 to 4 GVHD occurred in 43% of patients with matched donors, 69% with single allele-mismatched donors, and 71% with double allele-mismatched donors; grades 3 to 4 GVHD occurred in 22%, 43%, and 64%, respectively. On multivariate analysis, the relative risk of grades 2 to 4 GVHD was 2.2 (95% CI, 1.1-4.5; P = .03) with a single allele mismatch and 2.7 (95% CI, 1.2-6.0; P = .02) with a double allele mismatch. The relative risks of grades 3 to 4 GVHD were 3.0 (95% CI, 1.2-7.6; P = .02) and 5.0 (95% CI, 1.9-12.6; P = .001), respectively. Day 100 treatment-related mortality was also adversely affected by allelic mismatching, occurring in 21% of those with matched donors, 50% with single allele-mismatched donors, and 42% with double allele-mismatched donors (P = .02), but overall survival at day 180 did not differ significantly among the 3 groups. Tacrolimus does not abrogate the adverse impact of allele mismatching at HLA-DRB1 and HLA-DQB1 on the risk of moderate-to-severe acute GVHD.Biol Blood Marrow Transplant 2000;6(2A):190-7

Unique quadruplex structure and interaction of an RNA aptamer against bovine prion protein

RNA aptamers against bovine prion protein (bPrP) were obtained, most of the obtained aptamers being found to contain the r(GGAGGAGGAGGA) (R12) sequence. Then, it was revealed that R12 binds to both bPrP and its β-isoform with high affinity. Here, we present the structure of R12. This is the first report on the structure of an RNA aptamer against prion protein. R12 forms an intramolecular parallel quadruplex. The quadruplex contains G:G:G:G tetrad and G(:A):G:G(:A):G hexad planes. Two quadruplexes form a dimer through intermolecular hexad–hexad stacking. Two lysine clusters of bPrP have been identified as binding sites for R12. The electrostatic interaction between the uniquely arranged phosphate groups of R12 and the lysine clusters is suggested to be responsible for the affinity of R12 to bPrP. The stacking interaction between the G:G:G:G tetrad planes and tryptophan residues may also contribute to the affinity. One R12 dimer molecule is supposed to simultaneously bind the two lysine clusters of one bPrP molecule, resulting in even higher affinity. The atomic coordinates of R12 would be useful for the development of R12 as a therapeutic agent against prion diseases and Alzheimer's disease

Preclinical testing of the glycogen synthase kinase-3β inhibitor tideglusib for rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common childhood soft tissue sarcoma. RMS often arise from myogenic precursors and displays a poorly differentiated skeletal muscle phenotype most closely resembling regenerating muscle. GSK3β is a ubiquitously expressed serine-threonine kinase capable of repressing the terminal myogenic differentiation program in cardiac and skeletal muscle. Recent unbiased chemical screening efforts have prioritized GSK3β inhibitors as inducers of myodifferentiation in RMS, suggesting efficacy as single agents in suppressing growth and promoting self-renewal in zebrafish transgenic embryonal RMS (eRMS) models in vivo. In this study, we tested the irreversible GSK3β-inhibitor, tideglusib for in vivo efficacy in patient-derived xenograft models of both alveolar rhabdomyosarcoma (aRMS) and eRMS. Tideglusib had effective on-target pharmacodynamic efficacy, but as a single agent had no effect on tumor progression or myodifferentiation. These results suggest that as monotherapy, GSK3β inhibitors may not be a viable treatment for aRMS or eRMS