Identifying serious underlying diagnoses among patients with brief resolved unexplained events (BRUEs): a Canadian cohort study.

OBJECTIVE: To describe the demographics and clinical outcomes of infants with brief resolved unexplained events (BRUE). DESIGN: A retrospective cohort study. SETTING: 11 centres within the Canadian Paediatric Inpatient Research Network. PATIENTS: Patients presenting to the emergency department (ED) following a BRUE (2017-2021) were eligible, when no clinical cause identified after a thorough history and physical examination. MAIN OUTCOME MEASURES: Serious underlying diagnosis (requiring prompt identification) and event recurrence (within 90 days). RESULTS: Of 1042 eligible patients, 665 were hospitalised (63.8%), with a median stay of 1.73 days. Diagnostic tests were performed on 855 patients (82.1%), and 440 (42.2%) received specialist consultations. In total, 977 patients (93.8%) were categorised as higher risk BRUE per the American Academy of Pediatrics guidelines. Most patients (n=551, 52.9%) lacked an explanatory diagnosis; however, serious underlying diagnoses were identified in 7.6% (n=79). Epilepsy/infantile spasms were the most common serious underlying diagnoses (2.0%, n=21). Gastro-oesophageal reflux was the most common non-serious underlying diagnosis identified in 268 otherwise healthy and thriving infants (25.7%). No instances of invasive bacterial infections, arrhythmias or metabolic disorders were found. Recurrent events were observed in 113 patients (10.8%) during the index visit, and 65 patients had a return to ED visit related to a recurrent event (6.2%). One death occurred within 90 days. CONCLUSIONS: There is a low risk for a serious underlying diagnosis, where the majority of patients remain without a clear explanation. This study provides evidence-based risk for adverse outcomes, critical information to be used when engaging in shared decision-making with caregivers.

Online Learning in Medical Student Clerkship: A Survey of Student Perceptions and Future Directions.

Background The coronavirus disease 2019 (COVID-19) pandemic had a major impact on medical education with clerkship students abruptly removed from clinical activities in 2020 and hastily immersed in online learning to maintain medical education. In 2022, students returned to in-person clinical experiences, but synchronous learning sessions continued online with extensive use of asynchronous online resources. This change offers a unique opportunity to gather information about students' perspectives regarding the acceptability and effectiveness of online learning strategies. This study aims to explore the clerkship student experience with the integration of online learning and in-person learning into formalized educational sessions in clerkship. Methodology The authors administered an online survey to clerkship students at the Cumming School of Medicine at the University of Calgary, Canada in spring 2022. The survey consisted of primarily Likert-style questions to explore the perceived effectiveness of various online learning strategies. Results are reported as the proportion selecting "quite effective" or "extremely effective." Results A total of 89 students responded to the survey (57.4% of graduating class). For synchronous online learning, case-based learning was perceived as the most effective teaching strategy (61.8%), and audience response systems were the most effective strategy for improving audience engagement (70.1%). For asynchronous online learning, interactive cases (84.9%) and student-developed online study guides (83.6%) were perceived as the most effective. Students held varying perceptions regarding how online learning impacted their well-being. When considering future clerkship curricula, the majority of clerkship students preferred a blend of in-person and online learning. Conclusions This study identified that most clerkship students prefer a hybrid of in-person and online learning and that ideal online learning curricula could include case-based learning, audience response systems, and a variety of asynchronous learning resources. These results can guide curriculum development and design at other medical institutions.

An Adolescent Female With Concurrent Presentation of Autoimmune Hepatitis and Secondary Syphilis.

We describe concurrent diagnoses of autoimmune hepatitis (AIH) and secondary syphilis in a 17-year-old adolescent with jaundice, with possible syphilitic hepatitis (SH) excluded after a thorough investigation. Our patient presented with a several-day history of malaise, progressive jaundice, and vomiting. She disclosed being sexually active and requested testing for sexually transmitted infections. Her subsequent investigations demonstrated acute hepatitis with a positive antinuclear antibody and elevated IgG. She also tested positive for syphilis with a reactive rapid plasma regain and treponema pallidum particle agglutination assay. We considered 2 etiologies for her elevated liver enzymes: syphilitic hepatitis and AIH. AIH was confirmed on liver biopsy, establishing the first reported pediatric case of concurrent AIH and secondary syphilis. Syphilis is hypothesized to be an infectious trigger for AIH.

Medical Education Blog and Podcast Utilization During the COVID-19 Pandemic.

Introduction The coronavirus disease 2019 (COVID-19) pandemic disrupted traditional in-person learning models. Free Open Access Medical (FOAM) education resources naturally filled this void, so we evaluated how medical blog and podcast utilization changed during the early months of the pandemic. Methods Academic medical podcast and blog producers were surveyed on blog and podcast utilization immediately before (January-March 2020) and after (April-May 2020) the COVID-19 pandemic declaration and subsequent lockdown. Utilization is quantified in terms of blog post pageviews and podcast downloads. Linear regression was used to estimate the effect of publication during the COVID-19 period on 30-day downloads or pageviews. A linear mixed model was developed to confirm this relationship after adjustment for independent predictors of higher 30-day downloads or pageviews, using the podcast or blog as a random intercept. Results Compared to the pre-pandemic period, downloads and pageviews per unique blog and podcast publication significantly increased for blogs (median 30-day pageviews 802 to 1860, p<0.0001) but not for podcasts (median 30-day downloads 2726 to 1781, p=0.27). Publications that contained COVID-19 content were strongly associated with higher monthly utilization (ß=7.21, 95% CI 6.29-8.14 p<0.001), and even non-COVID-19 material had higher utilization in the early pandemic (median 30-day downloads/pageviews 868 to 1380, p<0.0001). Discussion The increased blog pageviews during the early months of the COVID-19 pandemic demonstrated the important role of blogs in rapid knowledge translation. Podcasts did not experience a similar increase in utilization.

Current practices and policies regarding the use of high-flow nasal cannula on general pediatric inpatient wards in Canada.

OBJECTIVES: High-flow nasal cannula (HFNC) oxygen therapy has become a common treatment for respiratory conditions in children. To our knowledge, no study has described practice patterns for HFNC on pediatric inpatient wards in Canada. The aim of this study was to survey current practices and policies regarding the use of HFNC on the ward in children's hospitals in Canada. METHODS: We conducted a web-based survey of Pediatric Hospital Medicine section chiefs in major tertiary care hospitals in Canada. The primary outcome was the proportion of hospitals that use HFNC on the general pediatric ward. Secondary outcomes included indications for HFNC, initial and maximum flow rates, maximum FiO2, method of nutrition delivery while on HFNC, level of nursing and respiratory therapist care required, criteria for pediatric intensive care unit transfer, and subjective successes and challenges of implementing a ward-based HFNC policy. RESULTS: The section chief survey response rate was 100% (15/15). Eight centres (53%) allowed the use of HFNC outside of an intensive care setting. Six centres initiated HFNC on the ward, while two centres only accepted patients after HFNC had been initiated in an intensive care setting. Other practices and policies varied considerably from centre to centre. CONCLUSION: Our study reveals that approximately half of tertiary children's hospitals in Canada currently use HFNC on the ward and utilize a range of practices and policies. Other centres are considering implementation. Further research is needed to inform best practices for HFNC therapy, support stewardship of health care resources, and promote safe patient care.

Peripherally acting µ-opioid receptor antagonists for treatment of opioid-induced constipation in children.

BACKGROUND AND OBJECTIVE: Opioid-induced constipation (OIC) is a common and important problem in paediatric palliative care, critical care, and postoperative settings. Treatment for OIC is often ineffective and limited by enteral intake. A new class of drugs called peripherally acting mu-opioid receptor antagonists (PAMORAs) have been shown to be effective treatments of OIC in adults, including the agents methylnaltrexone and naloxegol. Data in children are limited to several small case reports, mostly in the palliative care setting. The goal of this study was to evaluate the effectiveness and safety of methylnaltrexone and naloxegol in hospitalized children, including those with critical illness. METHODS: We conducted a retrospective study of all children admitted to the Stollery Children's Hospital in Edmonton (Canada) who received either methylnaltrexone or naloxegol for OIC. The primary outcome was median time to first bowel movement (BM) after the first dose of PAMORA. RESULTS: A total of 27 patients were included in the study. Kaplan-Meier survival analysis showed the median time to the first BM after the first dose of PAMORA was 15.5 hours. Seventeen (63%) patients had laxation within 24 hours of first dose. No significant adverse events were observed. CONCLUSION: This study is the largest to date to evaluate efficacy and safety of PAMORAs in children. Future studies should be prospective and include larger numbers of patients with critical illness and postoperative OIC as indications for treatment.

Preparing residents to deal with human trafficking.

BACKGROUND: Victims of human trafficking (HT) are predisposed to numerous health concerns. Many encounter health care practitioners during captivity, but awareness and knowledge among front-line physicians is low. Limited data exist on attempts to address this within residency training programmes. Formal curriculum time in residency is limited and online modules may be a useful educational option. METHODS: Residents in family medicine, emergency medicine and general paediatrics at the University of Alberta were invited to participate. They completed short surveys to assess knowledge both before and after completing an online learning module either individually (n = 15) or in a facilitated session (n = 17). Baseline and post-intervention changes in self-reported and tested knowledge were assessed. RESULTS: Thirty-two residents completed the pre-intervention survey: only 6% self-identified as somewhat knowledgeable on HT and 16% knew the red flags used to identify victims. Eighty-one percent wanted this topic incorporated into residency training, but only 6% and 25% had received education previously in residency or medical school, respectively. Thirteen percent were comfortable supporting victims, and 6% reported knowing how to provide support. Twenty residents completed the post-intervention survey, with improvements in both self-reported (p < 0.001) and tested (p = 0.005) knowledge of HT. Residents also reported being more prepared to identify victims (p < 0.001), more comfortable supporting victims (p < 0.001) and more confident in knowing how to support victims (p < 0.001). DISCUSSION: Baseline HT knowledge in residents providing first-contact care appears limited. Residency programmes should consider providing more HT education in order to improve competency in care. Although an online module was shown to be effective, protected time might be necessary for the widespread adoption of online education delivery.

Medical Student Perceptions of On-Call Modalities: A Focus Group Study.

Phenomenon: The call component of clerkship presents students with unique opportunities and challenges. Clerkship programs employ various call modalities, including traditional call, night float, and evening call. The impact of these call models on the student experience has not been explored in depth. Approach: Focus groups were conducted with 4th-year medical students, exploring their multidimensional experiences with various call modalities during clerkship. Transcripts were analyzed using thematic analysis. Findings: Thirty-nine students participated in 6 focus groups. Four overarching themes were identified: (a) educational value conferred by clinical exposure and teaching, (b) maintaining quality of life and developing features of burnout, (c) formation of professional identity via relationships with team members, and (d) perceived quality of patient care provided. Students associated evening call with burnout and poor educational value but also better patient continuity of care. Night float and traditional call contributed to a sense of team bonding and had enhanced perceived educational value while on call but resulted in loss of formal academic teaching time. Insights: Call modality impacts student learning, well-being, professional identity formation, and patient care; however, trade-off among these elements exists across all call models. Enhancing the value of student call experience may be achieved by implementation of various purposeful changes. These may include creating consistency between student and resident call schedules, maximizing recovery time between call shifts, and avoiding scheduling of students for call prior to academic sessions.

Enhanced delivery of topically-applied formulations following skin pre-treatment with a hand-applied, plastic microneedle array.

The purpose of this work is to characterize microchannels created by polymeric microneedles, applied by hand, and to demonstrate enhanced delivery of topically applied formulations of lidocaine hydrochloride and methylprednisolone sodium succinate (MPSS). 3M's Microstructured Transdermal System (MTS) arrays were applied to domestic swine to demonstrate reliability of penetration, depth of penetration and durability of the structures to repeat application and high force. Tissue levels of lidocaine and MPSS following topical application with and without microneedle pretreatment were determined by HPLC-MS analysis following digestion of biopsies. Almost all microneedles penetrate the stratum corneum upon hand force application. The depth of penetration varies from <100µm to nearly 150µm depending on the application force and the firmness of the underlying tissue. The arrays show excellent durability to repeated in-vivo application, with less than 5% of the structures evidencing even minimal tip bending after 16 applications. Under extreme force against a rigid surface, the microneedles bend but do not break. A lidocaine hydrochloride formulation applied topically in-vivo showed ~340% increase in local tissue levels when the MTS arrays were used to twice pre-treat the skin prior to applying the drug. Local delivery of a topically applied formulation of MPSS was over one order of magnitude higher when the application site was twice pre-treated with the MTS array. 3M's MTS array (marketed as 3M(TM) Microchannel Skin System) provides repeatable and robust penetration of the stratum corneum and epidermis and enhances delivery of some formulations such as lidocaine hydrochloride.

A two one-sided parametric tolerance interval test for control of delivered dose uniformity--part 3--investigation of robustness to deviations from normality.

The robustness of the parametric tolerance interval test, which was proposed by the Food and Drug Administration for control of delivered dose uniformity in orally inhaled and nasal drug products, is investigated in this article using different scenarios for deviations from a univariate normal distribution. The studied scenarios span a wide range of conditions, the purpose of which is to provide an understanding of how the test performs depending on the nature and degree of the deviation from normality. Operating characteristic curves were generated to compare the performance of the test for different types of distributions (normal and non-normal) having the same proportion of doses in the tails (on one or both sides) outside the target interval. The results show that, in most cases, non-normality does not increase the probability of accepting a batch of unacceptable quality (i.e., the test is robust) except in extreme situations, which do not necessarily represent commercially viable products. The results also demonstrate that, in the case of bimodal distributions where the life-stage means differ from each other by up to 24% label claim, the test's criterion on life-stage means does not affect pass rates because the tolerance interval portion of the test reacts to shifting means as well.

A two one-sided parametric tolerance interval test for control of delivered dose uniformity. Part 1--characterization of FDA proposed test.

The FDA proposed a parametric tolerance interval (PTI) test at the October 2005 Advisory Committee meeting as a replacement of the attribute (counting) test for delivered dose uniformity (DDU), published in the 1998 draft guidance for metered dose inhalers (MDIs) and dry powder inhalers (DPIs) and the 2002 final guidance for inhalation sprays and intranasal products. This article (first in a series of three) focuses on the test named by the FDA "87.5% coverage." Unlike a typical two-sided PTI test, which controls the proportion of the DDU distribution within a target interval (coverage), this test is comprised of two one-sided tests (TOST) designed to control the maximum amount of DDU values in either tail of the distribution above and below the target interval. Through simulations, this article characterizes the properties and performance of the proposed PTI-TOST under different scenarios. The results show that coverages of 99% or greater are needed for a batch to have acceptance probability 98% or greater with the test named by the FDA "87.5% coverage" (95% confidence level), while batches with 87.5% coverage have less than 1% probability of being accepted. The results also illustrate that with this PTI-TOST, the coverage requirement for a given acceptance probability increases as the batch mean deviates from target. The accompanying articles study the effects of changing test parameters and the test robustness to deviations from normality.

A two one-sided parametric tolerance interval test for control of delivered dose uniformity--part 2--effect of changing parameters.

This article examines the effects of changing parameters in the test which was proposed by the FDA at the October 2005 Advisory Committee meeting for confirming delivered dose uniformity in orally inhaled and nasal drug products. This article is an extension of the characterization study presented in an accompanying article (Part 1). The goal of this study is to understand how parameters of the test affect the test performance. The effects of changing test parameters such as target interval, maximum allowable proportion in the tail area, and sample size are examined. The results show that changing the maximum allowable tail area and/or the target interval have the largest impact on the test outcomes, i.e., probability of acceptance for a given batch mean and standard deviation. The presented information may provide potential users of the test with a set of tools for optimizing the test characteristics for a particular product.

Microsphere bead arrays and sequence validation of 5/7/9T genotypes for multiplex screening of cystic fibrosis polymorphisms.

The development of simple and rapid methods for the detection of the common genetic mutations associated with cystic fibrosis (CF) requires access to positive-control samples including the 5/7/9T variants of intron 8. We used PCR and a simple multiplex bead-array assay to identify 5/7/9T control samples from 29 commercially available DNA samples. Unpurified PCR products were directly hybridized to color-coded beads containing allele-specific capture probes for 5/7/9T detection. The performance of the assay was investigated using reverse-complement oligonucleotides, individual PCR products, and multiplex PCR products for 5/7/9T detection within a complex CFTR screening assay. Samples were genotyped by grouping the relative signal intensities from each capture probe. Of 29 commercially available DNA samples analyzed, 2 5T/7T, 2 5T/9T, 9 7T/9T, 11 7T/7T, and 5 9T/9T genotypes were identified. The genotype within each sample group was confirmed by DNA sequencing. The assay was compatible with the analysis of 10 to 1000 ng of genomic DNA isolated from whole blood and allowed for the separate identification of primary CFTR mutations from reflex variants. The correct identification of positive controls demonstrated the utility of a simple bead-array assay and provided accessible samples for assay optimization and for routine quality control in the clinical laboratory.