Genetic Mutations, Birth Lengths, Weights and Head Circumferences of Children with IGF-I Receptor Defects. Comparison with other Congenital Defects in the GH/IGF-I axis.

BACKGROUND: In recent years more and more genetic defects along the GHRH-GH-IGF-I axis have been reported. Mutations of the IGF-I receptor (R) are a rare abnormality of whom only the heterozygote progenies survive. OBJECTIVES: To summarize, from the literature, data on birth length, weight and head circumference of neonates with IGF-I-R mutations, and to correlate the data with that of other types of mutations in the GH/IGF-I axis. SUBJECTS: Sixty seven neonates from 24 published articles were included and forty seven different mutations of the IGF-I (R) located on chromosome 15 have been identified. RESULTS: Mean (±SD) birth length (BL), available for 26, (10 M, 16F) neonates with a gestational age of 34-41weeks, was 44.2±4cm; one was premature (30cm at 31 weeks). There was a significant correlation between birth length and gestational age (GA) r=0.71 (p>.001). Mean birth weight (BW) of 41 neonates (18M, 23F) was 2388±743gr. Two premature neonates weighed 650gr and 950gr respectively. The BW correlated significantly with gestational age, (males: r=0.68; p=0.007, females: r=0.49; p=0.024). The BMI of 25 neonates ranged from 6 to 13. In 22 records marked microcephaly was ascertained or stated. Nine of 16 mothers were short (133 -148cm), m±SD = 150.5±7.3cm.

Homozygous MED25 mutation implicated in eye-intellectual disability syndrome.

Genetic syndromes involving both brain and eye abnormalities are numerous and include syndromes such as Warburg micro syndrome, Kaufman oculocerebrofacial syndrome, Cerebro-oculo-facio-skeletal syndrome, Kahrizi syndrome and others. Using exome sequencing, we have been able to identify homozygous mutation p.(Tyr39Cys) in MED25 as the cause of a syndrome characterized by eye, brain, cardiac and palatal abnormalities as well as growth retardation, microcephaly and severe intellectual disability in seven patients from four unrelated families, all originating from the same village. The protein encoded by MED25 belongs to Mediator complex or MED complex, which is an evolutionary conserved multi-subunit RNA polymerase II transcriptional regulator complex. The MED25 point mutation is located in the von Willebrand factor type A (MED25 VWA) domain which is responsible for MED25 recruitment into the Mediator complex; co-immunoprecipitation experiment demonstrated that this mutation dramatically impairs MED25 interaction with the Mediator complex in mammalian cells.

Acknowledging and Addressing Microaggressions: A Virtual Experiential Learning Approach for Faculty.

Introduction: Although the ACGME and other accrediting organizations are increasingly emphasizing the importance of clinical learning environments that value diversity, equity, and inclusion, faculty development surrounding behavioral skills that promote inclusivity in the learning environment still needs cultivation. We designed a virtual longitudinal faculty development curriculum focused on direct observation, feedback, and practice of behavioral skills to acknowledge and address microaggressions in the learning environment. Methods: We used Kern's six steps of curriculum development to create four voluntary virtual workshops offered twice throughout the academic year, with topics including: (1) recognizing and naming microaggressions, (2) apologizing when harm has been experienced, (3) setting expectations surrounding microaggressions, and (4) debriefing microaggressions. Participant learners included residency program directors, associate program directors, and other leaders across all medical and surgical departments from one institution. Results: Thirty-one faculty from 10 departments participated in this yearlong curriculum. Pre- and postworkshop surveys analyzed participants' self-assessments of confidence and comfort in applying learned skills. Participants were more confident in openly naming bias, delivering expectations surrounding microaggressions, and debriefing microaggressions with learners. Participants also reported greater comfort in apologizing to learners when harm has occurred in public, in person, and electronically. Discussion: To create an inclusive learning environment, faculty can increase their comfort and confidence with addressing bias and microaggressions through practice and feedback. Our curriculum demonstrates how experiential learning allows for continual practice to solidify a new skill.

Changing the conversation: impact of guidelines designed to optimize interprofessional facilitation of simulation-based team training.

BACKGROUND: Interprofessional simulation-based team training (ISBTT) is commonly used to optimize interprofessional teamwork in healthcare. The literature documents the benefits of ISBTT, yet effective interprofessional collaboration continues to be challenged by complex hierarchies and power dynamics. Explicitly addressing these issues during ISBTT may help participants acquire skills to navigate such challenges, but guidelines on how to do this are limited. METHODS: We applied an educational design research approach to develop and pilot structured facilitator guidelines that explicitly address power and hierarchy with interprofessional teams. We conducted this work in a previously established ISBTT program at our institution, between September 2020 and December 2021. We first reviewed the literature to identify relevant educational theories and developed design principles. We subsequently designed, revised, and tested guidelines. We used qualitative thematic and content analysis of facilitator interviews and video-recording of IBSTT sessions to evaluate the effects of the guidelines on the pre- and debriefs. RESULTS: Qualitative content analysis showed that structured guidelines shifted debriefing participation and content. Debriefings changed from physician-led discussions with a strong focus on medical content to conversations with more equal participation by nurses and physicians and more emphasis on teamwork and communication. The thematic analysis further showed how the conversation during debriefing changed and how interprofessional learning improved after the implementation of the guidelines. While power and hierarchy were more frequently discussed, for many facilitators these topics remained challenging to address. CONCLUSION: We successfully created and implemented guidelines for ISBTT facilitators to explicitly address hierarchy and power. Future work will explore how this approach to ISBTT impacts interprofessional collaboration in clinical practice.

Incidence of Hemodynamic Changes Following Intravenous Acetaminophen Administration in Critically Ill Pediatric Patients.

OBJECTIVE: Acetaminophen is a commonly administered analgesic and antipyretic medication that is generally well-tolerated. Recent studies in critically ill adults and subsets of pediatric patients with underlying cardiac disease identify an association between adverse hemodynamic effects with intravenous (IV) acetaminophen. However, the data may not be generalizable to a broader population of critically ill children. The objective of this study was to determine the incidence of hemodynamic changes associated with IV acetaminophen administration in critically ill pediatric medical-surgical patients. METHODS: This was a retrospective observational study of all patients 18 years of age and younger who received at least 1 dose of IV acetaminophen in a pediatric intensive care unit at a quaternary care medical center, between July and December 2018. The primary outcome was the incidence of hypotension, defined as a decrease in mean arterial pressure (MAP) by at least 15% from baseline. Potential risk factors for IV acetaminophen-associated hypotension were assessed. RESULTS: A total of 212 patients received 492 doses of IV acetaminophen. The primary endpoint of hypotension occurred following 24% of doses. An intervention for hypotension, primarily fluid resuscitation, was required for 11.9% of the dose-associated hypotension events. Patients receiving vasoactive infusions had more frequent dose-associated hypotension events than those not receiving infusions; however, no other potential risk factors were identified. CONCLUSIONS: The incidence of hypotension observed in critically ill pediatric patients after IV acetaminophen administration is clinically relevant. Large placebo-controlled trial and further study of the risk factors and mechanism of this hemodynamic change are warranted.

Using Simulation to Teach Learners in Health Care Behavioral Skills Related to Diversity, Equity, and Inclusion: A Scoping Review.

SUMMARY STATEMENT: Bias is commonplace in the health care environment and can negatively impact patients and their health outcomes. Simulation has long been shown to be an effective teaching tool for communication skills in health care, but it has rarely been used to deliver concrete behavioral skills that address issues of diversity, equity, and inclusion (DEI). This scoping review examines 23 published articles surrounding the use of simulation in health care education to impart behavioral skills that reduce bias and promote DEI. Included articles described various behavioral skills including communication, history-taking, and system/community-level advocacy. The most commonly used simulation modality to teach these skills included the use of simulated participants (16 articles, 70%). The main DEI topics addressed in the trainings included sexual orientation/gender identity, language, and culture/ethnicity. Based on findings from this review, the authors suggest recommendations for educators who are considering teaching DEI-related skills through simulation.

A case of severe acidosis in a 12-month-old: Succinyl-CoA:3-ketoacid-CoA transferase deficiency with OXCT1 gene mutations.

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency is a rare autosomal recessive disorder that results in severe ketoacidosis due to a defect in ketone utilization. We describe a case of a 12-month-old infant presenting with severe metabolic acidosis, ketosis, and hyperammonemia, a combination of symptoms suggestive of an inborn error of metabolism. Genetic testing found our patient had a homozygous variant in the OXCT1 gene, c.1543A>G (p.Met515Val). This was the first identified case of SCOT deficiency at our institution. We share our acute management strategies for initial stabilization in the intensive care unit, as well as our approach to preventing morning ketosis after discharge using uncooked cornstarch.

Standardized Patients' Perspectives on Bias in Student Encounters.

PURPOSE: Standardized patient (SP) encounters are widely used in health professional education to evaluate trainees' clinical skills. Prior literature suggests that bias can influence the evaluations of student learners in SP-student encounters. Understanding how SPs perceive bias in their work and how they view their role in mitigating or perpetuating bias in simulation is an important first step in addressing bias in the SP-student encounter. METHOD: Researchers designed a qualitative interview study and conducted 16 semistructured interviews with SPs at the University of California, San Francisco Kanbar Simulation Center from July through September of 2020. Participants were selected using purposive sampling. The interviews were transcribed and analyzed by researchers using inductive thematic analysis. Researchers met iteratively to reconcile codes and identify themes. RESULTS: SPs identified bias occurring in multiple directions: SP-to-student, student-to-SP, student-to-character, and SP-to-character. SPs were hesitant to label their own biases and instead used words such as "comfort" or "preference." SPs reported little bias from students, because students were being evaluated and therefore behaving carefully. Additionally, SPs perceived bias in the implementation of health care simulation, which manifests as underrepresentation of certain groups amongst actors and character descriptions. Most SPs felt that they should play a role in mitigating bias in SP-student encounters, including addressing bias that occurs, challenging stereotypes, teaching about cultural differences, and/or being conscious of bias in their assessments of learners. CONCLUSIONS: In the SP-student encounter, bias can occur on many levels and between many individuals, including between the SP and the character they are portraying. Identifying the areas in which bias can exist can help simulation educators mitigate bias.

Serotonin Syndrome in an Infant Associated With Linezolid and Opioid Use.

Most reported cases of serotonin syndrome involve either a selective serotonin reuptake inhibitor (SSRI) or monoamine oxidase inhibitors (MAOI) and at least 1 other serotonergic medication or exposure to a single serotonin-augmenting drug. This case report describes serotonin syndrome occurring in association with the concomitant use of the antibiotic linezolid and opioids, specifically methadone, in a pediatric intensive care unit patient. The patient developed hyperpyrexia, muscle rigidity, clonus, and multiorgan dysfunction within 48 hours of receiving linezolid while concurrently on methadone. This drug-drug interaction is a rare cause of serotonin syndrome that has only been described 1 other time in the adult literature. This report raises awareness of this rare but serious and potentially lethal complication of serotonin syndrome associated with concomitant linezolid and opioid use. Timely consideration of the diagnosis in the setting of hyperpyrexia can facilitate prompt initiation of targeted therapies to prevent sequela.

The effects of rudeness, experience, and perspective-taking on challenging premature closure after pediatric ICU physicians receive hand-off with the wrong diagnosis: a randomized controlled simulation trial.

OBJECTIVES: Rudeness exposure has been shown to inhibit diagnostic performance. The effects of rudeness on challenging a handed-off diagnostic error has not been studied. METHODS: This was a randomized controlled study of attending, fellow, and resident physicians in a tertiary care pediatric ICU. Participants underwent a standardized simulation that started with the wrong diagnosis in hand-off. The hand-off was randomized to neutral vs. rude. Participants were not informed of the randomization nor diagnostic error prior to the simulation. Perspective taking questionnaires were administrated for each participant. Primary outcome was challenging diagnostic error post-simulation. Secondary outcomes included rate and frequency of diagnostic error challenge during simulation. RESULTS: Among 41 simulations (16 residents, 14 fellows, and 11 attendings), the neutral group challenged the diagnostic error more than the rude group (neutral: 71%, rude: 55%, p=0.28). The magnitude of this trend was larger among resident physicians only, although not statistically significant (neutral: 50%, rude: 12.5%, p=0.11). Experience was associated with a higher percentage of challenging diagnostic error (residents: 31%, fellows: 86%, attendings: 82%, p=0.003). Experienced physicians were faster to challenge diagnostic error (p<0.0003), and experience was associated with a greater frequency of diagnostic error challenges (p<0.0001). High perspective taking scores were also associated with 1.63 times more diagnostic error challenges (p=0.007). CONCLUSIONS: Experience was strongly associated with likelihood to challenge diagnostic error. Rudeness may disproportionally hinder diagnostic performance among less experienced physicians. Perspective taking merits further research in possibly reducing diagnostic error momentum.