Developmental health of Canadian kindergarten children with teacher-reported asthma between 2010 and 2015: A population-level cross-sectional study.

Asthma can impact children's quality of life. It is unclear how asthma is associated with the developmental health (i.e. a broad range of skills and abilities associated with growth and development) of young children at school entry. The goals of this cross-sectional, population-level study were to: (1) investigate the association between teacher-reported asthma and children's concurrent indicators of developmental health (developmental vulnerability); and (2) explore whether school absences and functional impairments modified this association. Participants were a Canadian population-based sample of 564 582 kindergarten children (Mage = 5.71 years, SD = 0.32, 51.3 % male) with data on the Early Development Instrument (EDI) collected between 2010 and 2015. Adjusted binary logistic regressions were conducted to address the objectives. From the sample, 958 (0.2 %) children were identified as having a diagnosis of asthma. These children were absent on average 9.4 days and 53.5 % had functional impairments (vs. 6.7 days absent and 15.9 % with functional impairments in children without asthma). After controlling for demographic characteristics, children with asthma had between 1.51 and 2.42 higher odds of being developmentally vulnerable. Only the presence of functional impairments modified this relationship and only for physical health and well-being. In this large, population-based sample of Canadian kindergarten children, few teachers reported knowledge of their students' asthma diagnosis. Among teacher-reported cases, asthma was a risk factor for developmental vulnerability in the domain of physical health and well-being only. Functional impairments may therefore be more detrimental for child development at school entry than asthma alone.

Diagnosis and clinical presentation of two individuals with a rare TCF20 pathogenic variant.

TCF20-associated neurodevelopmental disorder (TAND) is a rare and phenotypically variable genetic condition. Common features include intellectual disability, neurobehavioural concerns, postnatal tall stature and hypotonia.Two unrelated early adolescent males were referred to genetics for assessment of developmental delay. The first male of Caucasian descent had a history of autism spectrum disorder (ASD), mitral valve prolapse and subtle craniofacial dysmorphisms. The second male of Somali descent had a history of intellectual disability, thick corpus callosum and ASD. Whole-exome sequencing revealed a pathogenic variant in TCF20 in both individuals. Further testing revealed that the former individual's mother was mosaic for the TCF20 pathogenic variant.We report two individuals with TCF20 pathogenic variants presenting with unique findings, including thick corpus callosum, family history of mosaicism and cardiac anomalies. These examples expand the TAND phenotype, describe associated dysmorphism in a minority group and highlight the importance of rare disease research.

An Advanced Nursing Directive for Children With Suspected Appendicitis: Protocol for a Quality Improvement Feasibility Study.

BACKGROUND: Pediatric appendicitis accounts for an estimated 7% to 10% of abdominal pain cases in the emergency department (ED). The diagnosis is time-consuming, and the investigative process depends on physician assessment, resulting in delays in diagnosis and therapeutic management. The utility of an advanced nursing directive (AND) to expedite this process is unclear and needs further exploration. OBJECTIVE: This study aims to describe key components of ED flow in patients with suspected appendicitis seen at a pediatric ED and pilot a directive that allows ED nurses to perform an order set that includes blood work, urine tests, analgesics, fluids, and an abdominal-pelvis ultrasound prior to physician assessment. METHODS: This study involves conducting a retrospective chart review alongside a quality improvement initiative to compare key ED flow metrics before and after AND implementation. Primary outcome measures include median time from ED triage assessment to ultrasound completion, analgesia administration, blood work results, and time to disposition (consult or discharge), alongside other key ED flow metrics for suspected appendicitis. Secondary outcomes will involve patient and caretaker satisfaction surveys. Descriptive statistics will be used to summarize the data. For differences in proportions, a chi-square test will be used. The Student t test will be used for continuous variables. A variable-controlled run chart will be performed to assess impact on ED flow metrics. Patient and family satisfaction surveys are administered immediately after the directive encounter and 7 days afterward. RESULTS: There are currently 3900 patients who have been screened, 344 patients who have been enrolled, and 90 patients who have received the medical directive since implementation in June 2020. Interim results on reduction of time to diagnostic and therapeutic ED flow parameters and satisfaction surveys are expected to be published in February 2022. The final study endpoint will be in June 2022. CONCLUSIONS: This study proposes a novel protocol for improving the diagnosis and treatment of suspected pediatric appendicitis through implementation of an evidence-based AND. This model may provide a standardized, international pathway for management of common pediatric and adult emergencies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/33158.

Targeted genome editing in vivo corrects a Dmd duplication restoring wild-type dystrophin expression.

Tandem duplication mutations are increasingly found to be the direct cause of many rare heritable diseases, accounting for up to 10% of cases. Unfortunately, animal models recapitulating such mutations are scarce, limiting our ability to study them and develop genome editing therapies. Here, we describe the generation of a novel duplication mouse model, harboring a multi-exonic tandem duplication in the Dmd gene which recapitulates a human mutation. Duplication correction of this mouse was achieved by implementing a single-guide RNA (sgRNA) CRISPR/Cas9 approach. This strategy precisely removed a duplication mutation in vivo, restored full-length dystrophin expression, and was accompanied by improvements in both histopathological and clinical phenotypes. We conclude that CRISPR/Cas9 represents a powerful tool to accurately model and treat tandem duplication mutations. Our findings will open new avenues of research for exploring the study and therapeutics of duplication disorders.