Acute respiratory infections in hospitalised infants with congenital heart disease.

OBJECTIVES: To assess the overall burden and outcomes of acute respiratory infections in paediatric inpatients with congenital heart disease (CHD). METHODS: This is a retrospective cross-sectional study of non-neonates <1 year with CHD in the Kid's Inpatient Database from 2012. We compared demographics, clinical characteristics, cost, length of stay, and mortality rate for those with and without respiratory infections. We also compared those with respiratory infections who had critical CHD versus non-critical CHD. Multi-variable regression analyses were done to look for associations between respiratory infections and mortality, length of stay, and cost. RESULTS: Of the 28,696 infants with CHD in our sample, 26% had respiratory infections. Respiratory infection-associated hospitalisations accounted for $440 million in costs (32%) for all CHD patients. After adjusting for confounders including severity, mortality was higher for those with respiratory infections (OR 1.5, p = 0.003), estimated mean length of stay was longer (14.7 versus 12.2 days, p < 0.001), and estimated mean costs were higher ($53,760 versus $46,526, p < 0.001). Compared to infants with respiratory infections and non-critical CHD, infants with respiratory infections and critical CHD had higher mortality (4.5 versus 2.3%, p < 0.001), longer mean length of stay (20.1 versus 15.5 days, p < 0.001), and higher mean costs ($94,284 versus $52,585, p < 0.001). CONCLUSION: Acute respiratory infections are a significant burden on infant inpatients with CHD and are associated with higher mortality, costs, and longer length of stay; particularly in those with critical CHD. Future interventions should focus on reducing the burden of respiratory infections in this population.

Giants among Cnidaria: Large Nuclear Genomes and Rearranged Mitochondrial Genomes in Siphonophores.

Siphonophores (Cnidaria: Hydrozoa) are abundant predators found throughout the ocean and are important constituents of the global zooplankton community. They range in length from a few centimeters to tens of meters. They are gelatinous, fragile, and difficult to collect, so many aspects of the biology of these roughly 200 species remain poorly understood. To survey siphonophore genome diversity, we performed Illumina sequencing of 32 species sampled broadly across the phylogeny. Sequencing depth was sufficient to estimate nuclear genome size from k-mer spectra in six specimens, ranging from 0.7 to 2.3 Gb, with heterozygosity estimates between 0.69% and 2.32%. Incremental k-mer counting indicates k-mer peaks can be absent with nearly 20× read coverage, suggesting minimum genome sizes range from 1.4 to 5.6 Gb in the 25 samples without peaks in the k-mer spectra. This work confirms most siphonophore nuclear genomes are large relative to the genomes of other cnidarians, but also identifies several with reduced size that are tractable targets for future siphonophore nuclear genome assembly projects. We also assembled complete mitochondrial genomes for 33 specimens from these new data, indicating a conserved gene order shared among nonsiphonophore hydrozoans, Cystonectae, and some Physonectae, revealing the ancestral mitochondrial gene order of siphonophores. Our results also suggest extensive rearrangement of mitochondrial genomes within other Physonectae and in Calycophorae. Though siphonophores comprise a small fraction of cnidarian species, this survey greatly expands our understanding of cnidarian genome diversity. This study further illustrates both the importance of deep phylogenetic sampling and the utility of k-mer-based genome skimming in understanding the genomic diversity of a clade.

Creating Culturally Adapted Multilingual Materials for Research.

Patients who speak languages other than English are frequently excluded from research. This exclusion exacerbates inequities, biases results, and may violate federal regulations and research ethics. Language justice is the right to communicate in an individual's preferred language to address power imbalances and promote equity. To promote language justice in research, we propose a method to translate and culturally-adapt multifaceted research materials into multiple languages simultaneously. Our method involves a multistep approach, including professional translation, review by bilingual expert panels to refine and reach consensus, and piloting or cognitive interviews with patients and families. Key differences from other translation approaches (eg, the World Health Organization) include omitting back-translation, given its limited utility in identifying translation challenges, and limiting expert panelist and piloting-participant numbers for feasibility. We detail a step-by-step approach to operationalizing this method and outline key considerations learned after utilizing this method to translate materials into 8 languages other than English for an ongoing multicenter pediatric research study on family safety-reporting. Materials included family brochures, surveys, and intervention materials. This approach took ∼6 months overall at a cost of <$2000 per language (not including study personnel costs). Key themes across the project included (1) tailor scope to timeline, budget, and resources, (2) thoughtfully design English source materials, (3) identify and apply guiding principles throughout the translation and editing process, and (4) carefully review content and formatting to account for nuances across multiple languages. This method balances feasibility and rigor in translating participant-facing materials into multiple languages simultaneously, advancing language justice in research.

Variation in Inhaled Medication Use for Infants With Congenital Heart Disease and Bronchiolitis.

BACKGROUND AND OBJECTIVES: Current viral bronchiolitis guidelines exclude infants with congenital heart disease (CHD). Variations in the use of common therapeutics in this population and their associations with clinical outcomes are unknown. Our objective was to evaluate variations in (1) the use of ß-2-agonists and hypertonic saline across hospitals among infants with CHD hospitalized with bronchiolitis, and (2) hospital-level associations between medication use and outcomes. METHODS: We performed a multicenter retrospective cohort study using administrative data from 52 hospitals in the Pediatric Health Information System. We included infants ≤12 months old hospitalized from January 1, 2015 to June 30, 2019 for bronchiolitis with a secondary diagnosis of CHD. Primary exposures were the hospital-level proportion of days that patients received ß-2-agonists or hypertonic saline. Linear regression models assessed the association between the primary exposure and length of stay, 7-day readmission, mechanical ventilation use, and ICU utilization, adjusting for patient covariates and accounting for clustering by center. RESULTS: We identified 6846 index hospitalizations for bronchiolitis in infants with CHD. Overall, 43% received a ß-2-agonist, and 23% received hypertonic saline. The proportion of days with the use of ß-2-agonists (3.6% to 57.4%) and hypertonic saline (0.0% to 65.8%) varied widely across hospitals in our adjusted model. For both exposures, adjusted models revealed no association between days of use and patient outcomes. CONCLUSIONS: For children with CHD hospitalized with bronchiolitis, hospital-level use of ß-2-agonists and hypertonic saline varied widely, and their use was not associated with clinical outcomes.

Creation of an albino squid line by CRISPR-Cas9 and its application for in vivo functional imaging of neural activity.

Cephalopods are remarkable among invertebrates for their cognitive abilities, adaptive camouflage, novel structures, and propensity for recoding proteins through RNA editing. Due to the lack of genetically tractable cephalopod models, however, the mechanisms underlying these innovations are poorly understood. Genome editing tools such as CRISPR-Cas9 allow targeted mutations in diverse species to better link genes and function. One emerging cephalopod model, Euprymna berryi, produces large numbers of embryos that can be easily cultured throughout their life cycle and has a sequenced genome. As proof of principle, we used CRISPR-Cas9 in E. berryi to target the gene for tryptophan 2,3 dioxygenase (TDO), an enzyme required for the formation of ommochromes, the pigments present in the eyes and chromatophores of cephalopods. CRISPR-Cas9 ribonucleoproteins targeting tdo were injected into early embryos and then cultured to adulthood. Unexpectedly, the injected specimens were pigmented, despite verification of indels at the targeted sites by sequencing in injected animals (G0s). A homozygote knockout line for TDO, bred through multiple generations, was also pigmented. Surprisingly, a gene encoding indoleamine 2,3, dioxygenase (IDO), an enzyme that catalyzes the same reaction as TDO in vertebrates, was also present in E. berryi. Double knockouts of both tdo and ido with CRISPR-Cas9 produced an albino phenotype. We demonstrate the utility of these albinos for in vivo imaging of Ca2+ signaling in the brain using two-photon microscopy. These data show the feasibility of making gene knockout cephalopod lines that can be used for live imaging of neural activity in these behaviorally sophisticated organisms.

Yes, we CAM: Increasing physician communication about complementary and alternative medicine through electronic medical record prompts in a pediatric hospital.

BACKGROUND AND PURPOSE: Over half of patients utilize complementary and alternative medicine (CAM), yet fewer than 10 % of physicians inquire about use. This prospective cohort study sought to increase patient-provider communication about CAM through electronic medical record (EMR) prompts and education, as well as study concordance rates of physician and nursing CAM-related documentation. MATERIALS AND METHODS: Recordings in history and physical (H&P) documents authored by first-year pediatric residents were used as a proxy for communication. Rates of documentation were assessed at baseline, after the introduction of an EMR prompt, and after an educational intervention. Nursing documentation was compared with resident documents to assess rates of concordance regarding CAM-related documentation. RESULTS: Baseline CAM-related documentation rate was 24 % and increased to 50 % after introducing an EMR CAM prompt (p < 0.001). No significant change occurred after education: 38 % had CAM-related documentation (p = 0.09). Physician and nursing documentation concordance rates were 58 % at baseline, 48 % after introduction of prompts, and 35 % after introducing education. CONCLUSION: Visual cues alone may be effective in increasing patient-provider communication about CAM, though low concordance between physician and nursing documentation may suggest variability in how CAM is defined and inquired about.

Technology-Dependent Pediatric Inpatients at Children's Versus Nonchildren's Hospitals.

BACKGROUND AND OBJECTIVE: Technology-dependent children (TDC) are admitted to both children's hospitals (CHs) and nonchildren's hospitals (NCHs), where there may be fewer pediatric-specific specialists or resources. Our objective was to compare the characteristics of TDC admitted to CHs versus NCHs. METHODS: This was a multicenter, retrospective study using the 2012 Kids' Inpatient Database. We included patients aged 0 to 18 years with a tracheostomy, gastrostomy, and/or ventricular shunt. We excluded those who died, were transferred into or out of the hospital, had a length of stay (LOS) that was an extreme outlier, or had missing data for key variables. We compared patient and hospital characteristics across CH versus NCH using χ2 tests and LOS and cost using generalized linear models. RESULTS: In the final sample of 64 521 discharges, 55% of discharges of TDC were from NCHs. A larger proportion of those from CHs had higher disease severity (55% vs 49%; P < .001) and a major surgical procedure during hospitalization (28% vs 24%; P < .001). In an adjusted generalized linear model, the mean LOS was 4 days at both hospital types, but discharge from a CH was associated with a higher adjusted mean cost ($16 754 vs $12 023; P < .001). CONCLUSIONS: Because the majority of TDC are hospitalized at NCHs, future research on TDC should incorporate NCH settings. Further studies should investigate if some may benefit from regionalization of care or earlier transfer to a CH.

Highly Efficient Knockout of a Squid Pigmentation Gene.

Seminal studies using squid as a model led to breakthroughs in neurobiology. The squid giant axon and synapse, for example, laid the foundation for our current understanding of the action potential [1], ionic gradients across cells [2], voltage-dependent ion channels [3], molecular motors [4-7], and synaptic transmission [8-11]. Despite their anatomical advantages, the use of squid as a model receded over the past several decades as investigators turned to genetically tractable systems. Recently, however, two key advances have made it possible to develop techniques for the genetic manipulation of squid. The first is the CRISPR-Cas9 system for targeted gene disruption, a largely species-agnostic method [12, 13]. The second is the sequencing of genomes for several cephalopod species [14-16]. If made genetically tractable, squid and other cephalopods offer a wealth of biological novelties that could spur discovery. Within invertebrates, not only do they possess by far the largest brains, they also express the most sophisticated behaviors [17]. In this paper, we demonstrate efficient gene knockout in the squid Doryteuthis pealeii using CRISPR-Cas9. Ommochromes, the pigments found in squid retinas and chromatophores, are derivatives of tryptophan, and the first committed step in their synthesis is normally catalyzed by Tryptophan 2,3 Dioxygenase (TDO [18-20]). Knocking out TDO in squid embryos efficiently eliminated pigmentation. By precisely timing CRISPR-Cas9 delivery during early development, the degree of pigmentation could be finely controlled. Genotyping revealed knockout efficiencies routinely greater than 90%. This study represents a critical advancement toward making squid genetically tractable.

Medical errors in US pediatric inpatients with chronic conditions.

OBJECTIVE: To investigate the association between chronic conditions and iatrogenic medical errors in US pediatric inpatients. METHODS: The 2006 Kids' Inpatient Database (KID) was analyzed. Medical errors were defined by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Medical error rates per 100 hospital discharges and per 1000 inpatient days were calculated. Logistic regression models were fitted to study the association between number of chronic conditions and medical errors, controlling for patient characteristics, hospital characteristics, disease severity, and length of stay. RESULTS: In the 2006 KID, 22.3% of pediatric inpatients had 1 chronic condition, 9.8% had 2 chronic conditions, and 12.0% had ≥ 3 chronic conditions. The overall medical error rate per 100 discharges was 3.0 (95% confidence interval [CI]: 2.8-3.3); it was 5.3 (95% CI: 4.9-5.7) in children with chronic conditions and 1.3 (95% CI: 1.2-1.3) in children without chronic conditions. The medical error rate per 1000 inpatient days was also higher in children with chronic conditions. The association between chronic conditions and medical errors remained statistically significant in logistic regression models adjusting for patient characteristics, hospital characteristics, disease severity, and length of stay. In the adjusted model, the odds ratio of medical errors for children with 1 chronic condition was 1.40 (95% CI: 1.32-1.48); for children with 2 conditions, the OR was 1.55 (95% CI: 1.45-1.66); and for children with 3 conditions, the OR was 1.66 (95% CI: 1.53-1.81). CONCLUSIONS: The number of chronic conditions was significantly associated with iatrogenic medical errors in pediatric inpatients.