The Impact of IT on Team Situational Awareness during In-Hospital Cardiac Arrest Interventions: Implications for Team Coordination

Effective team coordination during in-hospital cardiac arrest interventions is central to improving treatment outcomes. However, research highlights many obstacles to effective coordination during resuscitation attempts, including communication breakdowns and lack of information sharing. These factors are also associated with degradation in team situational awareness. Furthermore, resuscitation teams must interact with many IT to provide adequate treatment. While IT use supports the creation of task-oriented knowledge, the extent to which it enables shared knowledge and team situational awareness is not clear. Our study reveals that IT promotes team situational awareness in two ways: by providing shared access to information, and by aligning members’ higher-level situational awareness. However, some team-oriented processes may be hindered by IT featuring high data density and detailed information displays. Our results contribute to IS literature on team coordination by revealing the role of IT in enabling team situational awareness and coordination in dynamic and complex environments

In-situ simulations to detect patient safety threats during in-hospital cardiac arrest

Introduction: Errors during treatment may affect patient outcomes and can include errors in treatment algorithms, teamwork, and system errors. In-hospital cardiac arrests (IHCA) require immediate and effective treatment, and delays are known to reduce survival. In-situ simulation is a tool that can be used to study emergency responses, including IHCA. We investigated system errors discovered during unannounced in-situ simulated IHCA. Method: This multicenter cohort study included unannounced, full-scale IHCA in-situ simulations followed by a debriefing based on PEARLS with plus-delta used in the analysis phase. Simulations and debriefings were video-recorded for subsequent analysis. System errors observed were categorized by thematic analysis and analyzed for clinical implications. Errors related to treatment algorithm and clinical performance were excluded. Results: We conducted 36 in-situ simulations across 4 hospitals with a total discovery of 30 system errors. On average, we discovered 0.8 system errors per simulation within the categories: human, organizational, hardware, or software errors. Of these, 25 errors (83%) had direct treatment consequences. System errors caused treatment delays in 15 cases, a need for alternative actions in 6 cases, omission of actions in 4 cases, and other consequences in 5 cases. Conclusion: Using unannounced in-situ simulations, we identified almost one system error per simulation, and most of these errors were deemed to impact treatment negatively. The errors affected treatment by either causing delays, need for alternative treatment options, or omitting treatment actions. We suggest that hospitals focus on the need for regular testing of the emergency response by conducting full-scale unannounced in-situ simulations. This should be a priority to improve patient safety and care

POU3F3-related disorder:Defining the phenotype and expanding the molecular spectrum

POU3F3 variants cause developmental delay, behavioral problems, hypotonia and dysmorphic features. We investigated the phenotypic and genetic landscape, and genotype–phenotype correlations in individuals with POU3F3-related disorders. We recruited unpublished individuals with POU3F3 variants through international collaborations and obtained updated clinical data on previously published individuals. Trio exome sequencing or single exome sequencing followed by segregation analysis were performed in the novel cohort. Functional effects of missense variants were investigated with 3D protein modeling. We included 28 individuals (5 previously published) from 26 families carrying POU3F3 variants; 23 de novo and one inherited from an affected parent. Median age at study inclusion was 7.4 years. All had developmental delay mainly affecting speech, behavioral difficulties, psychiatric comorbidities and dysmorphisms. Additional features included gastrointestinal comorbidities, hearing loss, ophthalmological anomalies, epilepsy, sleep disturbances and joint hypermobility. Autism, hearing and eye comorbidities, dysmorphisms were more common in individuals with truncating variants, whereas epilepsy was only associated with missense variants. In silico structural modeling predicted that all (likely) pathogenic variants destabilize the DNA-binding region of POU3F3. Our study refined the phenotypic and genetic landscape of POU3F3-related disorders, it reports the functional properties of the identified pathogenic variants, and delineates some genotype–phenotype correlations.</p

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders

Background: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype–phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations. Methods: We tested our hypothesis by considering gene families that have multiple members with an enrichment of de novo variants among NDDs, as determined by previous meta-analyses. One of these gene families is the heterogeneous nuclear ribonucleoproteins (hnRNPs), which has 33 members, five of which have been recently identified as NDD genes (HNRNPK, HNRNPU, HNRNPH1, HNRNPH2, and HNRNPR) and two of which have significant enrichment in our previous meta-analysis of probands with NDDs (HNRNPU and SYNCRIP). Utilizing protein homology, mutation analyses, gene expression analyses, and phenotypic characterization, we provide evidence for variation in 12 HNRNP genes as candidates for NDDs. Seven are potentially novel while the remaining genes in the family likely do not significantly contribute to NDD risk. Results: We report 119 new NDD cases (64 de novo variants) through sequencing and international collaborations and combined with published clinical case reports. We consider 235 cases with gene-disruptive single-nucleotide variants or indels and 15 cases with small copy number variants. Three hnRNP-encoding genes reach nominal or exome-wide significance for de novo variant enrichment, while nine are candidates for pathogenic mutations. Comparison of HNRNP gene expression shows a pattern consistent with a role in cerebral cortical development with enriched expression among radial glial progenitors. Clinical assessment of probands (n = 188–221) expands the phenotypes associated with HNRNP rare variants, and phenotypes associated with variation in the HNRNP genes distinguishes them as a subgroup of NDDs. Conclusions: Overall, our novel approach of exploiting gene families in NDDs identifies new HNRNP-related disorders, expands the phenotypes of known HNRNP-related disorders, strongly implicates disruption of the hnRNPs as a whole in NDDs, and supports that NDD subtypes likely have shared molecular pathogenesis. To date, this is the first study to identify novel genetic disorders based on the presence of disorders in related genes. We also perform the first phenotypic analyses focusing on related genes. Finally, we show that radial glial expression of these genes is likely critical during neurodevelopment. This is important for diagnostics, as well as developing strategies to best study these genes for the development of therapeutics.Medicine, Faculty ofOther UBCNon UBCMedical Genetics, Department ofPediatrics, Department ofReviewedFacult

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.

BackgroundWith the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations.MethodsWe tested our hypothesis by considering gene families that have multiple members with an enrichment of de novo variants among NDDs, as determined by previous meta-analyses. One of these gene families is the heterogeneous nuclear ribonucleoproteins (hnRNPs), which has 33 members, five of which have been recently identified as NDD genes (HNRNPK, HNRNPU, HNRNPH1, HNRNPH2, and HNRNPR) and two of which have significant enrichment in our previous meta-analysis of probands with NDDs (HNRNPU and SYNCRIP). Utilizing protein homology, mutation analyses, gene expression analyses, and phenotypic characterization, we provide evidence for variation in 12 HNRNP genes as candidates for NDDs. Seven are potentially novel while the remaining genes in the family likely do not significantly contribute to NDD risk.ResultsWe report 119 new NDD cases (64 de novo variants) through sequencing and international collaborations and combined with published clinical case reports. We consider 235 cases with gene-disruptive single-nucleotide variants or indels and 15 cases with small copy number variants. Three hnRNP-encoding genes reach nominal or exome-wide significance for de novo variant enrichment, while nine are candidates for pathogenic mutations. Comparison of HNRNP gene expression shows a pattern consistent with a role in cerebral cortical development with enriched expression among radial glial progenitors. Clinical assessment of probands (n = 188-221) expands the phenotypes associated with HNRNP rare variants, and phenotypes associated with variation in the HNRNP genes distinguishes them as a subgroup of NDDs.ConclusionsOverall, our novel approach of exploiting gene families in NDDs identifies new HNRNP-related disorders, expands the phenotypes of known HNRNP-related disorders, strongly implicates disruption of the hnRNPs as a whole in NDDs, and supports that NDD subtypes likely have shared molecular pathogenesis. To date, this is the first study to identify novel genetic disorders based on the presence of disorders in related genes. We also perform the first phenotypic analyses focusing on related genes. Finally, we show that radial glial expression of these genes is likely critical during neurodevelopment. This is important for diagnostics, as well as developing strategies to best study these genes for the development of therapeutics