Design and characteristics of the prophylactic intra-operative ventricular arrhythmia ablation in high-risk LVAD candidates (PIVATAL) trial.

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.

Feasibility and Consistency of Results with Deployment of an In-Line Filter for Exercise-Based Evaluations of Patients With Heart Failure During the Novel Coronavirus Disease-2019 Pandemic.

BACKGROUND: Exercise testing plays an important role in evaluating heart failure prognosis and selecting patients for advanced therapeutic interventions. However, concern for severe acute respiratory syndrome novel coronavirus-2 transmission during exercise testing has markedly curtailed performance of exercise testing during the novel coronavirus disease-2019 pandemic. METHODS AND RESULTS: To examine the feasibility to conducting exercise testing with an in-line filter, 2 healthy volunteer subjects each completed 2 incremental exercise tests, one with discrete stages of increasing resistance and one with a continuous ramp. Each subject performed 1 test with an electrostatic filter in-line with the system measuring gas exchange and air flow, and 1 test without the filter in place. Oxygen uptake and minute ventilation were highly consistent when evaluated with and without use of an electrostatic filter with a >99.9% viral efficiency. CONCLUSIONS: Deployment of a commercially available in-line electrostatic viral filter during cardiopulmonary exercise testing is feasible and provides consistent data compared with testing without a filter.

Finding the Unicorn, a New Mouse Model of Midfacial Clefting.

Human midfacial clefting is a rare subset of orofacial clefting and in severe cases, the cleft separates the nostrils splitting the nose into two independent structures. To begin to understand the morphological and genetic causes of midfacial clefting we recovered the Unicorn mouse line. Unicorn embryos develop a complete midfacial cleft through the lip, and snout closely modelling human midfacial clefting. The Unicorn mouse line has ethylnitrosourea (ENU)-induced missense mutations in Raldh2 and Leo1. The mutations segregate with the cleft face phenotype. Importantly, the nasal cartilages and surrounding bones are patterned and develop normal morphology, except for the lateral displacement because of the cleft. We conclude that the midfacial cleft arises from the failure of the medial convergence of the paired medial nasal prominences between E10.5 to E11.5 rather than defective cell proliferation and death. Our work uncovers a novel mouse model and mechanism for the etiology of midfacial clefting.

Localization of Tfap2ß, Casq2, Penk, Zic1, and Zic3 Expression in the Developing Retina, Muscle, and Sclera of the Embryonic Mouse Eye.

Optic development involves sequential interactions between several different tissue types, including the overlying ectoderm, adjacent mesoderm, and neural crest mesenchyme and the neuroectoderm. In an ongoing expression screen, we identified that Tfap2ß, Casq2, Penk, Zic1, and Zic3 are expressed in unique cell types in and around the developing eye. Tfap2ß, Zic1, and Zic3 are transcription factors, Casq2 is a calcium binding protein and Penk is a neurotransmitter. Tfap2ß, Zic1, and Zic3 have reported roles in brain and craniofacial development, while Casq2 and Penk have unknown roles. These five genes are expressed in the major tissue types in the eye, including the muscles, nerves, cornea, and sclera. Penk expression is found in the sclera and perichondrium. At E12.5 and E15.5, the extra-ocular muscles express Casq2, the entire neural retina expresses Zic1, and Zic3 is expressed in the optic disk and lip of the optic cup. The expression of Tfap2ß expanded from corneal epithelium to the neural retina between E12.5 to E15.5. These genes are expressed in similar domains as Hedgehog (Gli1, and Ptch1) and the Wnt (Lef1) pathways. The expression patterns of these five genes warrant further study to determine their role in eye morphogenesis.

Residents' perspective on professionalism in the learning environment.

All accrediting organizations for medical education in the US require teaching hospitals to ensure the learning environment fosters professionalism behaviors of trainees and faculty. This study analyzes the learning environment of professionalism from the perspective of residents. An on-line anonymous survey that explored the learning climate of professionalism was sent to all residents at the University of Virginia in 2013-14. Residents rated their personal commitment, their residency program's, and the institution's commitment to demonstrating professionalism behaviors, described professionalism education, reasons for not participating in curricular offerings, the quality of role modeling, and barriers to professionalism. Nearly half the residents completed the survey (47%, N = 365/771). Residents rated their personal commitment and commitment of their residency program significantly greater than the institution's commitment to demonstrating professionalism.(p < 0.001) They noted only 25% of faculty modeled these behaviors all the time; and more than half stated poor role modeling impacted their attitudes about the importance of professionalism. Other areas in need of improvement include communicating with patients with cultural differences, and inter-professional teamwork. Despite accreditation requirements for learning environments, residency curricula, and faculty development programs to promote professionalism, residents perceive their commitment to professionalism greater than the institution where they work.

Post-Exercise Oxygen Uptake Recovery Delay: A Novel Index of Impaired Cardiac Reserve Capacity in Heart Failure.

OBJECTIVES: This study sought to characterize the functional and prognostic significance of oxygen uptake (VO2) kinetics following peak exercise in individuals with heart failure (HF). BACKGROUND: It is unknown to what extent patterns of VO2 recovery following exercise reflect circulatory response during exercise in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). METHODS: We investigated patients (30 HFpEF, 20 HFrEF, and 22 control subjects) who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and a second distinct HF cohort (n = 106) who underwent noninvasive cardiopulmonary exercise testing with assessment of long-term outcomes. Fick cardiac output (CO) and cardiac filling pressures were measured at rest and throughout exercise in the initial cohort. A novel metric, VO2 recovery delay (VO2RD), defined as time until post-exercise VO2 falls permanently below peak VO2, was measured to characterize VO2 recovery kinetics. RESULTS: VO2RD in patients with HFpEF (median 25 s [interquartile range (IQR): 9 to 39 s]) and HFrEF (28 s [IQR: 2 to 52 s]) was in excess of control subjects (5 s [IQR: 0 to 7 s]; p < 0.0001 and p = 0.003, respectively). VO2RD was inversely related to cardiac output augmentation during exercise in HFpEF (ρ = -0.70) and HFrEF (ρ = -0.73, both p < 0.001). In the second cohort, VO2RD predicted transplant-free survival in univariate and multivariable Cox regression analysis (Cox hazard ratios: 1.49 and 1.37 per 10-s increase in VO2RD, respectively; both p < 0.005). CONCLUSIONS: Post-exercise VO2RD is an easily recognizable, noninvasively derived pattern that signals impaired cardiac output augmentation during exercise and predicts outcomes in HF. The presence and duration of VO2RD may complement established exercise measurements for assessment of cardiac reserve capacity.

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines.

Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study.

Using a computer simulation for teaching communication skills: A blinded multisite mixed methods randomized controlled trial.

OBJECTIVES: To assess advanced communication skills among second-year medical students exposed either to a computer simulation (MPathic-VR) featuring virtual humans, or to a multimedia computer-based learning module, and to understand each group's experiences and learning preferences. METHODS: A single-blinded, mixed methods, randomized, multisite trial compared MPathic-VR (N=210) to computer-based learning (N=211). Primary outcomes: communication scores during repeat interactions with MPathic-VR's intercultural and interprofessional communication scenarios and scores on a subsequent advanced communication skills objective structured clinical examination (OSCE). Multivariate analysis of variance was used to compare outcomes. SECONDARY OUTCOMES: student attitude surveys and qualitative assessments of their experiences with MPathic-VR or computer-based learning. RESULTS: MPathic-VR-trained students improved their intercultural and interprofessional communication performance between their first and second interactions with each scenario. They also achieved significantly higher composite scores on the OSCE than computer-based learning-trained students. Attitudes and experiences were more positive among students trained with MPathic-VR, who valued its providing immediate feedback, teaching nonverbal communication skills, and preparing them for emotion-charged patient encounters. CONCLUSIONS: MPathic-VR was effective in training advanced communication skills and in enabling knowledge transfer into a more realistic clinical situation. PRACTICE IMPLICATIONS: MPathic-VR's virtual human simulation offers an effective and engaging means of advanced communication training.

Do Variations in Agency Indirectly Affect Behavior with Others? An Analysis of Gaze Behavior.

In a group setting, it is possible for attributes of one group member to indirectly affect how other group members are perceived. In this paper, we explore whether one group member's agency (e.g. if they are real or virtual) can indirectly affect behavior with other group members. We also consider whether variations in the agency of a group member directly affects behavior with that group member. To do so, we examined gaze behavior during a team training exercise, in which sixty-nine nurses worked with a surgeon and an anesthesiologist to prepare a simulated patient for surgery. The agency of the surgeon and the anesthesiologist were varied between conditions. Nurses' gaze behavior was coded using videos of their interactions. Agency was observed to directly affect behavior, such that participants spent more time gazing at virtual teammates than human teammates. However, participants continued to obey polite gaze norms with virtual teammates. In contrast, agency was not observed to indirectly affect gaze behavior. The presence of a second human did not affect participants' gaze behavior with virtual teammates.

Relationships between preclinical course grades and standardized exam performance.

Success in residency matching is largely contingent upon standardized exam scores. Identifying predictors of standardized exam performance could promote primary intervention and lead to design insights for preclinical courses. We hypothesized that clinically relevant courses with an emphasis on higher-order cognitive understanding are most strongly associated with performance on United States Medical Licensing Examination Step exams and National Board of Medical Examiners clinical subject exams. Academic data from students between 2007 and 2012 were collected. Preclinical course scores and standardized exam scores were used for statistical modeling with multiple linear regression. Preclinical courses were categorized as having either a basic science or a clinical knowledge focus. Medical College Admissions Test scores were included as an additional predictive variable. The study sample comprised 795 graduating medical students. Median score on Step 1 was 234 (interquartile range 219-245.5), and 10.2 % (81/795) scored lower than one standard deviation below the national average (205). Pathology course score was the strongest predictor of performance on all clinical subject exams and Step exams, outperforming the Medical College Admissions Test in strength of association. Using Pathology score <75 as a screening metric for Step 1 score <205 results in sensitivity and specificity of 37 and 97 %, respectively, and a likelihood ratio of 11.9. Performance in Pathology, a clinically relevant course with case-based learning, is significantly related to subsequent performance on standardized exams. Multiple linear regression is useful for identifying courses that have potential as risk stratifiers.

Teaming Up with Virtual Humans: How Other People Change Our Perceptions of and Behavior with Virtual Teammates.

In this paper we present a study exploring whether the physical presence of another human changes how people perceive and behave with virtual teammates. We conducted a study (n = 69) in which nurses worked with a simulated health care team to prepare a patient for surgery. The agency of participants' teammates was varied between conditions; participants either worked with a virtual surgeon and a virtual anesthesiologist, a human confederate playing a surgeon and a virtual anesthesiologist, or a virtual surgeon and a human confederate playing an anesthesiologist. While participants perceived the human confederates to have more social presence (p <; 0.01), participants did not preferentially agree with their human team members. We also observed an interaction effect between agency and behavioral realism. Participants experienced less social presence from the virtual anesthesiologist, whose behavior was less in line with participants' expectations, when a human surgeon was present.

Using a Critical Incident Scenario With Virtual Humans to Assess Educational Needs of Nurses in a Postanesthesia Care Unit.

INTRODUCTION: During critical incidents, teamwork failures can compromise patient safety. This study provides evidence that virtual humans can be used in simulated critical incidents to assess the learning needs of health professionals, and provide important information that can inform the development of continuing education programs in patient safety. We explored the effectiveness of information transfer during a devolving medical situation between postanesthesia care unit (PACU) nurses and a virtual attending physician. METHODS: We designed a three-stage scenario: tutorial, patient transfer, and critical incident. We developed 2 checklists to assess information transfer: Critical Patient Information and Interprofessional Communication Skills. All participants were videotaped; 2 raters reviewed all videos and assessed performance using the checklists. RESULTS: Participants (n = 43) who completed all 3 stages scored 62.3% correct on critical patient information transfer and 61.6% correct on interprofessional communication skills. Almost 87% missed a fatal drug error. The checklists measured each item on a 1/0 (done/not) calculation. Additionally, no relationship was found between years of nursing experience and performance on either checklist. DISCUSSION: The PACU nurses in this study did not consistently share critical information with an attending (virtual) physician during a critical incident, and most missed a fatal dosage error. These findings strongly suggest a crucial need for additional structured team training among practicing health care teams, and they demonstrate the utility of using virtual humans to simulate team members.

What is appropriate to post on social media? Ratings from students, faculty members and the public.

OBJECTIVES: The purpose of this study was to ascertain what medical students, doctors and the public felt was unprofessional for medical students, as future doctors, to post on a social media site, Facebook(®) . The significance of this is that unprofessional content reflects poorly on a student, which in turn can significantly affect a patient's confidence in that student's clinical abilities. METHODS: An online survey was designed to investigate the perceptions of University of Michigan medical students, attending physicians and non-health care university-wide employees (that serves as a subset of the public) regarding mock medical students' Facebook(®) profile screenshots. For each screenshot, respondents used a 5-point Likert scale to rate 'appropriateness' and whether they would be 'comfortable' having students posting such content as their future doctors. RESULTS: Compared with medical students, faculty members and public groups rated images as significantly less appropriate (p < 0.001) and indicated that they would be less comfortable (p < 0.001) having posting students as future doctors. All three groups rated screenshots containing derogatory or private information about patients, followed by images suggesting marijuana use, as least appropriate. Images conveying intimate heterosexual couples were rated as most appropriate. Overall, the doctor group, females and older individuals were less permissive when compared with employee and student groups, males and younger individuals, respectively. CONCLUSIONS: The most significant conclusion of our study is that faculty members, medical students and the 'public' have different thresholds of what is acceptable on a social networking site. Our findings will prove useful for students to consider the perspectives of patients and faculty members when considering what type of content to post on their social media sites. In this way, we hope that our findings provide insight for discussions, awareness and the development of guidelines related to online professionalism for medical students.

Why are medical students 'checking out' of active learning in a new curriculum?

OBJECTIVES: The University of Virginia School of Medicine recently transformed its pre-clerkship medical education programme to emphasise student engagement and active learning in the classroom. As in other medical schools, many students are opting out of attending class and others are inattentive while in class. We sought to understand why, especially with a new student-centred curriculum, so many students were still opting to learn on their own outside of class or to disengage from educational activities while in class. METHODS: Focus groups were conducted with students from two classes who had participated in the new curriculum, which is designed to foster small-group and collaborative learning. The sessions were audio-recorded and then transcribed. The authors read through all of the transcripts and then reviewed them for themes. Quotes were analysed and organised by theme. RESULTS: Interview transcripts revealed candid responses to questions about learning and the learning environment. The semi-structured nature of the interviews enabled the interviewers to probe unanticipated issues (e.g. reasons for choosing to sit with friends although that diminishes learning and attention). A content analysis of these transcripts ultimately identified three major themes embracing multiple sub-themes: (i) learning studio physical space; (ii) interaction patterns among learners, and (iii) the quality of and engagement in learning in the space. CONCLUSIONS: Students' reluctance to engage in class activities is not surprising if classroom exercises are passive and not consistently well designed or executed as active learning exercises that students perceive as enhancing their learning through collaboration. Students' comments also suggest that their reluctance to participate regularly in class may be because they have not yet achieved the developmental level compatible with adult and active learning, on which the curriculum is based. Challenges include helping students better understand the nature of deep learning and their own developmental progress as learners, and providing robust faculty development to ensure the consistent deployment of higher-order learning activities linked with higher-order assessments.

Developmental changes in expression and biophysics of ion channels in the canine ventricle.

BACKGROUND: Developmental changes in the electrical characteristics of the ventricular myocardium are not well defined. This study examines the contribution of inwardly rectifying K(+) current (IK1), transient outward K(+) current (Ito), delayed rectifier K(+) currents (IKr and IKs) and sodium channel current (INa) to repolarization in the canine neonate myocardium. METHODS: Single myocytes isolated from the left ventricle of 2-3week old canine neonate hearts were studied using patch-clamp techniques. RESULTS: Neonate cells were ~6-fold smaller than those of adults (28.8±8.8 vs. 176±6.7pF). IK1 was larger in neonate myocytes and displayed a substantial inward component and an outward component with negative slope conductance, peaking at -60mV (4.13 pA/pF). IKr tail currents (at -40mV), were small (<20pA). IKs could not be detected, even after exposure to isoproterenol (100nM). Ito was also absent in the neonate, consistent with the absence of a phase 1 in the action potential. Peak INa, late INa and ICa were smaller in the neonate compared with adults. KCND3, KCNIP2 and KCNQ1 mRNA expression was half, while KCNH2 was equal and KCNJ2 was greater in the neonate when compared with adults. CONCLUSIONS: Two major repolarizing K(+) currents (IKs and Ito) present in adult ventricular cells are absent in the 2week old neonate. Peak and late INa are significantly smaller in the neonate. Our results suggest that the absence of these two currents in the neonate heart may increase the susceptibility to arrhythmias under certain long QT conditions.

Online learning applied to a course on rational therapeutics: an international comparison between final year students of two medical schools.

INTRODUCTION: Poor prescribing is probably the most common cause of preventable medication errors and many of these events involve junior doctors. In 2009, an electronic problem-based therapeutics course developed at the University of Michigan Medical School (UMMS) was translated and adapted for use at the University of Zagreb Medical School (UZMS). METHODS: After students from both schools took the course in 2010, we compared their responses with an online questionnaire addressing the course quality and its effectiveness. RESULTS: There were no statistically significant differences in the overall average grades awarded for the course (UZMS 4.11 ± 0.86 vs. UMMS 3.96 ± 0.93; 95% CI mean difference (MD) -0.36, 0.07; P = 0.175) with both student groups expressing high satisfaction rates with its quality, accessibility and overall design. UZMS students reported spending less time working through the course than their American colleagues (2.14 ± 1.01 vs. 2.89 ± 1.02 on a five point Likert scale; 95% CI MD 0.51, 0.99; P < 0.05). Furthermore, Croatian students indicated greater difficulty with course materials (3.54 ± 0.59 vs. 3.25 ± 0.59; 95% CI MD -0.42, -0.15; P < 0,05) and weekly multiple choice questions (3.83 ± 0.62 vs. 3.4 ± 0.61; 95% CI MD -0.58, -0.29; P < 0,05) compared with the UMMS students. CONCLUSION: It is possible to adapt and translate successfully whole online teaching resources and implement them internationally in different countries and health care systems, achieving similar, high student satisfaction rates while decreasing administrative and cost burdens. Web based learning may have great potential to offer a cost effective and safe environment in which prescribing skills can be improved.

Implementing a nurse-shadowing program for first-year medical students to improve interprofessional collaborations on health care teams.

Although physicians and nurses play critical roles in providing team-based collaborative care, the literature on current relationships between physicians and nurses in typical health care settings reveals troublesome characteristics that affect the quality of the patient care that they provide. Studies report communication failures, poor coordination, and fragmented care within and across organizations, which then have been associated with medication errors, patient safety issues, and patient deaths. Because the physician-nurse relationship is a critical component of a high-functioning patient care team, curricular interventions are needed to improve communication between physicians and nurses and to avoid professional conflict that can potentially compromise the quality of the patient care they offer.Currently, medical schools provide students with limited education and training on the roles of other health care professionals. In 2009, to begin addressing this need in the curriculum, the authors implemented a nurse-shadowing program at the University of Michigan Medical School. They set out to help first-year medical students learn more about the role of nurses in health care to positively influence their attitudes toward nurses and improve their understanding of nurses' roles in health care teams. Pre- and postprogram survey results revealed that medical students' attitudes toward nurses improved and their knowledge of the profession increased as a result of this intervention. In this article, the authors provide a description of the half-day program, evidence of its effectiveness, the implications of those findings, and future directions for teaching medical students about effectively working on interprofessional teams.