Acute asthma management with IV magnesium in obese, overweight and non-overweight inner-city children.

OBJECTIVE: IV Magnesium (IV Mg) is increasingly used as adjunctive therapy for asthma exacerbations. In obese patients, delays in recognition of asthma severity may lead to delays in IV Mg administration. Our objective was to examine whether timing of IV Mg administration varied by Body Mass Index (BMI) category and whether this relates to hospitalization course. METHODS: This is a retrospective chart review of IV Mg use for asthma in children 2-17 years of age hospitalized in an urban children's hospital. Weight status was categorized by BMI percentile for age. The primary outcome was time to IV Mg administration. Secondary outcomes included admission to the intensive care unit, time to discharge readiness and Length of Stay (LOS). Continuous variables were analyzed using Student's t-test or Mann-Whitney test, categorical variables with Chi-Square test or Fisher's exact test, as appropriate. A linear regression model examined factors related to time to IV Mg administration. RESULTS: In 2017, 361/698 (52%) of patients admitted with acute asthma received IV Mg. Of these, 210 patients met study criteria. Except for age, baseline characteristics did not vary by BMI category. No differences were found in Time to IV Mg, rates of admission to the intensive care unit, time to discharge readiness, or LOS comparing non-overweight to overweight or obese patients. CONCLUSIONS: In this sample of inner-city children who received IV Mg there were no differences in timing of IV Mg based on BMI category. Further work is needed to examine whether standardizing timing of IV Mg improves care.

Medical student remote eConsult participation during the COVID-19 pandemic.

BACKGROUND: Undergraduate medical education was severely impacted by the COVID-19 pandemic. As traditional clinical rotations were suspended, medical students quickly began alternative, novel educational experiences. Third-year medical students at an academic medical center were given the opportunity to join inpatient eConsult teams within the department of medicine. This study describes the development and implementation of this program as well as the experiences of student and faculty participants. METHODS: Student eConsult participation was rapidly developed and implemented within medical subspecialty teams in either infectious diseases (ID) or nephrology. Twelve third-year medical students and 15 subspecialty attendings participated in this program during an eight-week period from April 6 through May 29, 2020. Breadth of student clinical experience was assessed via review of clinical documentation and surveys. Participating students and attending physicians completed surveys to reflect upon their impressions of the program. Surveys were returned by nine students and eight faculty members. Survey responses were summarized with descriptive statistics. RESULTS: Over an eight-week period, student consultants wrote 126 notes on 100 patients; 74 of these patients (74%) were hospitalized with COVID-19. Student experiences were largely positive with most strongly agreeing that attendings promoted interactive and engaged learning (N = 8 of 8, 100%), that the experience helped to expand their knowledge about consultant roles (N = 6, 75%), and that they would participate in a remote eConsult program again if given the opportunity (N = 6, 75%). Faculty also were largely positive about the experience with most agreeing or strongly agreeing with the importance of teaching medical students about telehealth (N = 7 of 8, 88%) and eConsults (N = 6, 75%). In narrative responses, students and faculty agreed that teaching was a strength of the program whereas lack of in-person contact was a challenge. CONCLUSIONS: Rapid development of an inpatient eConsult-based educational experience for third-year medical students was feasible and successful. Student-consultants saw a range of pathology including COVID-19 and related complications. Students were satisfied with the program. They were able to develop a strong relationship with attendings while learning about the role of a consultant. Faculty agreed with the importance of teaching students about telehealth and eConsults specifically.

Serial follow-up of corrected QT interval in Rett syndrome.

AIM: To identify factors associated with baseline prolonged corrected QT (QTc) and higher risk of QTc prolongation during follow-up in patients with Rett syndrome (RTT). METHOD: A retrospective review of patients receiving an electrocardiogram (ECG) between June 2012 and June 2018 was performed. Age, methyl-CpG binding protein 2 gene (MECP2) mutation, RTT Severity Scale (RSSS) score, breathing abnormalities, seizure frequency, medications, and ECG parameters were collected. Prolonged QTc was defined as greater than or equal to 460ms. Comparisons at baseline and during follow-up were made. RESULTS: In total, 129 unique patients (all female) had 349 ECGs. At baseline, 12 (9.3%) had a prolonged QTc (median 474ms, interquartile range 470-486ms) and were more likely to have moderate/severe breathing abnormalities (66.7% vs 24.8%; p=0.005) and take selective serotonin reuptake inhibitors (SSRIs) (41.7% vs 15.4%; p=0.04). There was no difference in age, RSSS score, seizures, or mutation. Twenty-six developed prolonged QTc during a median follow-up of 1 year 7 months (interquartile range 0-3y 6mo). QTc prolongation was associated with p.(Thr158Met) mutation versus the remaining six common mutations (hazard ratio 4.1, 95% confidence interval 1.4-12.0; p=0.01) but not with age, RSSS score, seizures, breathing abnormalities, or SSRIs. INTERPRETATION: Breathing abnormalities and SSRIs were associated with baseline QTc prolongation and those with p.(Thr158Met) mutation were more likely to develop prolonged QTc over time. Identification of patients with prolonged QTc warrants increased clinical monitoring. WHAT THIS PAPER ADDS: Breathing abnormalities and selective serotonin reuptake inhibitors are associated with prolonged baseline corrected QT (QTc). Development of QTc prolongation is associated with the p.(Thr158Met) mutation.

A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.

Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.