Association between implementation of a coordinated care pathway in idiopathic scoliosis patients and a reduction in perioperative outcome disparities.

BACKGROUND: There are well-documented racial and ethnic disparities in treatment and perioperative outcomes for patients with adolescent idiopathic scoliosis. AIMS: We hypothesize that the implementation of a coordinated care pathway for pediatric patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis may be associated with a reduction in racial and ethnic disparities in perioperative outcomes. METHODS: This is a retrospective pre- and post-test cohort study of patients who underwent posterior spinal fusion for adolescent idiopathic scoliosis at our institution between July 1, 2013 and August 5, 2019. We implemented a coordinated care pathway in March 2015. Patient demographics included age, race, ethnicity, weight, gender, insurance status, ASA class, time between the date surgery was ordered and the date surgery occurred, degree of scoliosis, and the number of spinal levels fused. The primary outcome was length of stay. The secondary outcomes included transfusion rates, pain scores, and postoperative complications. Multivariable regression models compared outcome medians across race/ethnicity. Disparities were defined as the difference in adjusted outcomes by race/ethnicity. RESULTS: Four hundred twenty-four patients underwent posterior spinal fusion for adolescent idiopathic scoliosis at our institution (116 prepathway and 308 postpathway). The median length of stay of Black patients was 1.0 day (95% CI: 0.4, 1.5; p = .006) longer than White patients prepathway. Prepathway patients who self-identified as Other had a 1.2 (95% CI: 0.5, 1.9; p = .004) higher median average pain score on postoperative day 1 compared with White patients. On postoperative day 2, patients who identified as Other had 2.0 (95% CI: 0.8, 3.2; p = .005) higher pain score compared with White patients prepathway. Postpathway, there were no significant differences in outcomes by race/ethnicity. CONCLUSIONS: Our study supports the hypothesis that use of a coordinated care pathway is associated with a reduction in racial and ethnic disparities in length of stay and pain scores in pediatric patients undergoing posterior spinal fusion.

Crystal structures of monometallic dihydropyrimidinase and the human dihydroorotase domain K1556A mutant reveal no lysine carbamylation within the active site.

Dihydropyrimidinase (DHPase) is a member of the cyclic amidohydrolase family, which also includes allantoinase, dihydroorotase (DHOase), hydantoinase, and imidase. Almost all of these zinc metalloenzymes possess a binuclear metal center in which two metal ions are bridged by a post-translational carbamylated Lys. Crystal structure of Tetraodon nigroviridis DHPase reveals that one zinc ion is sufficient to stabilize Lys carbamylation. In this study, we found that one metal coordination was not sufficient to fix CO2 to the Lys in bacterial DHPase. We prepared and characterized mono-Zn DHPase from Pseudomonas aeruginosa (PaDHPase), and the catalytic activity of mono-Zn PaDHPase was not detected. The crystal structure of mono-Zn PaDHPase determined at 2.23 Šresolution (PDB entry 6AJD) revealed that Lys150 was no longer carbamylated. This finding indicated the decarbamylation of the Lys during the metal chelating process. To confirm the state of Lys carbamylation in mono-Zn PaDHPase in solution, mass spectrometric (MS) analysis was carried out. The MS result was in agreement with the theoretical value for uncarbamylated PaDHPase. Crystal structure of the human DHOase domain (huDHOase) K1556A mutant was also determined (PDB entry 5YNZ), and the structure revealed that the active site of huDHOase K1556A mutant contained one metal ion. Like mono-Zn PaDHPase, oxygen ligands of the carbamylated Lys were not required for Znα binding. Considering the collective data from X-ray crystal structure and MS analysis, mono-Zn PaDHPase in both crystalline state and solution was not carbamylated. In addition, structural evidences indicated that post-translational carbamylated Lys was not required for Znα binding in PaDHPase and in huDHOase.

Associations between intronic non-B DNA structures and exon skipping.

Non-B DNA structures are abundant in the genome and are often associated with critical biological processes, including gene regulation, chromosome rearrangement and genome stabilization. In particular, G-quadruplex (G4) may affect alternative splicing based on its ability to impede the activity of RNA polymerase II. However, the specific role of non-B DNA structures in splicing regulation still awaits investigation. Here, we provide a genome-wide and cross-species investigation of the associations between five non-B DNA structures and exon skipping. Our results indicate a statistically significant correlation of each examined non-B DNA structures with exon skipping in both human and mouse. We further show that the contributions of non-B DNA structures to exon skipping are influenced by the occurring region. These correlations and contributions are also significantly different in human and mouse. Finally, we detailed the effects of G4 by showing that occurring on the template strand and the length of G-run, which is highly related to the stability of a G4 structure, are significantly correlated with exon skipping activity. We thus show that, in addition to the well-known effects of RNA and protein structure, the relative positional arrangement of intronic non-B DNA structures may also impact exon skipping.

The impact of trans-regulation on the evolutionary rates of metazoan proteins.

Transcription factor (TF) and microRNA (miRNA) are two crucial trans-regulatory factors that coordinately control gene expression. Understanding the impacts of these two factors on the rate of protein sequence evolution is of great importance in evolutionary biology. While many biological factors associated with evolutionary rate variations have been studied, evolutionary analysis of simultaneously accounting for TF and miRNA regulations across metazoans is still uninvestigated. Here, we provide a series of statistical analyses to assess the influences of TF and miRNA regulations on evolutionary rates across metazoans (human, mouse and fruit fly). Our results reveal that the negative correlations between trans-regulation and evolutionary rates hold well across metazoans, but the strength of TF regulation as a rate indicator becomes weak when the other confounding factors that may affect evolutionary rates are controlled. We show that miRNA regulation tends to be a more essential indicator of evolutionary rates than TF regulation, and the combination of TF and miRNA regulations has a significant dependent effect on protein evolutionary rates. We also show that trans-regulation (especially miRNA regulation) is much more important in human/mouse than in fruit fly in determining protein evolutionary rates, suggesting a considerable variation in rate determinants between vertebrates and invertebrates.

Can ChatGPT help patients answer their otolaryngology questions?

Background: Over the past year, the world has been captivated by the potential of artificial intelligence (AI). The appetite for AI in science, specifically healthcare is huge. It is imperative to understand the credibility of large language models in assisting the public in medical queries. Objective: To evaluate the ability of ChatGPT to provide reasonably accurate answers to public queries within the domain of Otolaryngology. Methods: Two board-certified otolaryngologists (HZ, RS) inputted 30 text-based patient queries into the ChatGPT-3.5 model. ChatGPT responses were rated by physicians on a scale (accurate, partially accurate, incorrect), while a similar 3-point scale involving confidence was given to layperson reviewers. Demographic data involving gender and education level was recorded for the public reviewers. Inter-rater agreement percentage was based on binomial distribution for calculating the 95% confidence intervals and performing significance tests. Statistical significance was defined as p < .05 for two-sided tests. Results: In testing patient queries, both Otolaryngology physicians found that ChatGPT answered 98.3% of questions correctly, but only 79.8% (range 51.7%-100%) of patients were confident that the AI model was accurate in its responses (corrected agreement = 0.682; p < .001). Among the layperson responses, the corrected coefficient was of moderate agreement (0.571; p < .001). No correlation was noted among age, gender, or education level for the layperson responses. Conclusion: ChatGPT is highly accurate in responding to questions posed by the public with regards to Otolaryngology from a physician standpoint. Public reviewers were not fully confident in believing the AI model, with subjective concerns related to less trust in AI answers compared to physician explanation. Larger evaluations with a representative public sample and broader medical questions should immediately be conducted by appropriate organizations, governing bodies, and/or governmental agencies to instill public confidence in AI and ChatGPT as a medical resource. Level of Evidence: 4.

Prenatal Maternal Psychological Distress During the COVID-19 Pandemic and Newborn Brain Development.

Importance: Elevated maternal psychological distress during pregnancy is associated with altered fetal brain development. During the COVID-19 pandemic, prenatal maternal psychological distress more than doubled. Objective: To examine the association of the pandemic and rising maternal psychological distress with brain growth in newborns using quantitative 3-dimensional volumetric magnetic resonance imaging (MRI). Design, Setting, and Participants: This prospective cross-sectional study recruited mother-infant dyads at Children's National Hospital, Washington, DC, during the COVID-19 pandemic (June 1, 2020, to June 30, 2022) into a longitudinal infant brain development study and compared them with an existing normative healthy cohort (recruited March 1, 2014, to December 31, 2019). Exclusion criteria included multiple gestation pregnancy, known or suspected congenital infection, documented chromosomal abnormalities, or any maternal contraindication to MRI, as well as prenatal COVID-19 exposure. Infants with structural brain abnormalities or a postnatal confirmation of a genetic syndrome were excluded. Exposure: Psychological distress during COVID-19 pandemic. Main Outcomes and Measures: Prenatal maternal mental health was evaluated using the Spielberger State-Trait Anxiety Inventory and the Perceived Stress Scale. Neonates underwent nonsedated brain MRI. An ordinary least squares linear regression model was used to measure the differences in regional brain volumes of neonates born before vs during the pandemic with and without exposure to elevated prenatal maternal psychological distress after adjustment for neonatal sex and gestational age at MRI and maternal age and educational level. Results: A total of 159 mother-infant dyads were included in the analysis: 103 before and 56 during the pandemic (median gestational age of infants, 39.6 [IQR, 38.4-40.4] weeks; median maternal age, 34.5 [IQR, 31.0-37.0] years). Eighty-three infants (52.2%) were female. Among the mothers, 130 (81.8%) had a college degree and 87 (54.7%) had a graduate degree. Forty-four mothers (27.7%) identified as Asian, Hispanic, or multiracial; 27 (17.0%), as Black; and 88 (55.3%), as White. Scores on anxiety and stress measures were significantly increased in the pandemic cohort. Infants of mothers with elevated maternal distress showed median reductions in white matter (-0.36 [95% CI, -0.61 to -0.11] cm3; Q < .001), right hippocampal (-0.35 [95% CI, -0.65 to -0.06] cm3; Q = .04), and left amygdala (-0.49 [95% CI, -0.84 to -0.13] cm3; Q = .03) volumes compared with infants of mothers with low distress levels. After adjusting for the cohort effect of the pandemic, elevated trait anxiety remained significantly associated with decreased left amygdalar volumes (-0.71 [95% CI, -1.12 to -0.29]; Q < .001). Conclusions and Relevance: In this cross-sectional study of maternal-infant dyads prior to and during the COVID-19 pandemic, regional neonatal brain volumes were associated with elevated maternal psychological distress.

Evaluating the Current Ability of ChatGPT to Assist in Professional Otolaryngology Education.

Objective: To quantify ChatGPT's concordance with expert Otolaryngologists when posed with high-level questions that require blending rote memorization and critical thinking. Study Design: Cross-sectional survey. Setting: OpenAI's ChatGPT-3.5 Platform. Methods: Two board-certified otolaryngologists (HZ, RS) input 2 sets of 30 text-based questions (open-ended and single-answer multiple-choice) into the ChatGPT-3.5 model. Responses were rated on a scale (correct, partially correct, incorrect) by each Otolaryngologist working simultaneously with the AI model. Interrater agreement percentage was based on binomial distribution for calculating the 95% confidence intervals and performing significance tests. Statistical significance was defined as P < .05 for 2-sided tests. Results: In testing open-ended questions, the ChatGPT model had 56.7% of initially answering questions with complete accuracy, and 86.7% chance of answer with some accuracy (corrected agreement = 80.1%; P < .001). For repeat questions, ChatGPT improved to 73.3% with complete accuracy and 96.7% with some accuracy (corrected agreement = 88.8%; P < .001). For multiple-choice questions, the ChatGPT model performed substantially worse (43.3% correct). Conclusion: ChatGPT currently does not provide reliably accurate responses to sophisticated questions in Otolaryngology. Professional societies must be aware of the potential of this tool and prevent unscrupulous use during test-taking situations and consider guidelines for clinical scenarios. Expert clinical oversight is still necessary for myriad use cases (eg, hallucination).

A Quality Improvement Initiative to Improve Pediatric Discharge Medication Safety and Efficiency.

Medication errors are a leading safety concern, especially for families with limited English proficiency and health literacy, and patients discharged on multiple medications with complex schedules. Integration of a multilanguage electronic discharge medication platform may help decrease medication errors. This quality improvement (QI) project's primary aim (process measure) was to increase utilization in the electronic health record (EHR) of the integrated MedActionPlanPro (MAP) for cardiovascular surgery and blood and marrow transplant patients at hospital discharge and for the first clinic follow-up visit to 80% by July 2021. Methods: This QI project occurred between August 2020 and July 2021 on 2 subspecialty pediatric acute care inpatient units and respective outpatient clinics. An interdisciplinary team developed and implemented interventions, including integration of MAP within EHR; the team tracked and analyzed outcomes for discharge medication matching, and efficacy and safety MAP integration occurred with a go-live date of February 1, 2021. Statistical process control charts tracked progress. Results: Following the implementation of the QI interventions, there was an increase from 0% to 73% in the utilization of the integrated MAP in the EHR across the acute care cardiology unit-cardiovascular surgery/blood and marrow transplant units. The average user hours per patient (outcome measure) decreased 70% from the centerline of 0.89 hours during the baseline period to 0.27 hours. In addition, the medication matching between Cerner inpatient and MAP inpatient increased significantly from baseline to postintervention by 25.6% (P < 0.001). Conclusion: MAP integration into the EHR was associated with improved inpatient discharge medication reconciliation safety and provider efficiency.

Magnetic Resonance Spectroscopy of Brain Metabolism in Fetuses With Congenital Heart Disease.

BACKGROUND: Congenital heart disease (CHD) remains a significant risk factor for neurologic injury because altered fetal hemodynamics may be unable to support typical brain development during critical periods of growth and maturation. OBJECTIVES: The primary objective was to assess differences in the cerebral biochemical profile between healthy fetuses and fetuses with complex CHD and to relate these with infant outcomes. METHODS: Pregnant participants underwent fetal magnetic resonance imaging with cerebral proton magnetic resonance spectroscopy acquisitions as part of a prospective observational study. Cerebral metabolites of N-acetyl aspartate, creatine, choline, myo-inositol, scyllo-inositol, lactate, and relevant ratios were quantified using LCModel. RESULTS: We acquired 503 proton magnetic resonance spectroscopy images (controls = 333; CHD = 170) from 333 participants (controls = 221; CHD = 112). Mean choline levels were higher in CHD compared with controls (CHD 2.47 IU [Institutional Units] ± 0.44 and Controls 2.35 IU ± 0.45; P = 0.02), whereas N-acetyl aspartate:choline ratios were lower among CHD fetuses compared with controls (CHD 1.34 ± 0.40 IU vs controls 1.44 ± 0.48 IU; P = 0.001). Cerebral lactate was detected in all cohorts but increased in fetuses with transposition of the great arteries and single-ventricle CHD (median: 1.63 [IQR: 0.56-3.27] in transposition of the great arteries and median: 1.28 [IQR: 0-2.42] in single-ventricle CHD) compared with 2-ventricle CHD (median: 0.79 [IQR: 0-1.45]). Cerebral lactate also was associated with increased odds of death before discharge (OR: 1.75; P = 0.04). CONCLUSIONS: CHD is associated with altered cerebral metabolites in utero, particularly in the third trimester period of pregnancy, which is characterized by exponential brain growth and maturation, and is associated with survival to hospital discharge. The long-term neurodevelopmental consequences of these findings warrant further study.

Evolution of cis-regulatory elements in yeast de novo and duplicated new genes.

BACKGROUND: New genes that originate from non-coding DNA rather than being duplicated from parent genes are called de novo genes. Their short evolution time and lack of parent genes provide a chance to study the evolution of cis-regulatory elements in the initial stage of gene emergence. Although a few reports have discussed cis-regulatory elements in new genes, knowledge of the characteristics of these elements in de novo genes is lacking. Here, we conducted a comprehensive investigation to depict the emergence and establishment of cis-regulatory elements in de novo yeast genes. RESULTS: In a genome-wide investigation, we found that the number of transcription factor binding sites (TFBSs) in de novo genes of S. cerevisiae increased rapidly and quickly became comparable to the number of TFBSs in established genes. This phenomenon might have resulted from certain characteristics of de novo genes; namely, a relatively frequent gain of TFBSs, an unexpectedly high number of preexisting TFBSs, or lower selection pressure in the promoter regions of the de novo genes. Furthermore, we identified differences in the promoter architecture between de novo genes and duplicated new genes, suggesting that distinct regulatory strategies might be employed by genes of different origin. Finally, our functional analyses of the yeast de novo genes revealed that they might be related to reproduction. CONCLUSIONS: Our observations showed that de novo genes and duplicated new genes possess mutually distinct regulatory characteristics, implying that these two types of genes might have different roles in evolution.

MetaABC--an integrated metagenomics platform for data adjustment, binning and clustering.

SUMMARY: MetaABC is a metagenomic platform that integrates several binning tools coupled with methods for removing artifacts, analyzing unassigned reads and controlling sampling biases. It allows users to arrive at a better interpretation via series of distinct combinations of analysis tools. After execution, MetaABC provides outputs in various visual formats such as tables, pie and bar charts as well as clustering result diagrams. AVAILABILITY: MetaABC source code and documentation are available at http://bits2.iis.sinica.edu.tw/MetaABC/ CONTACT: dywang@gate.sinica.edu.tw; hktsai@iis.sinica.edu.tw SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Slips, Trips, and Falls: A Quality Improvement Initiative.

Employee safety and the reduction of Days Away, Restricted, or Transferred are a focus of the Solutions for Patient Safety Network. One significant contributor to the Days Away, Restricted, or Transferred rate at Children's National Hospital is employee slips, trips, or falls. Methods: Children's National Hospital implemented a multidisciplinary quality improvement with executive leadership vision and support. We implemented quality techniques (including Key Driver Diagrams, Pareto Charts, and continuous Plan-Do-Study-Act) and designed novel Environmental Services interventions. Results: Children's National Hospital achieved a 44.3% reduction in monthly average reported slips, trips, or fall events from baseline and sustained over a 2-year study period. Conclusion: A leadership-driven multidisciplinary approach to quality initiatives with team leaders capable of making and enacting real-time policy changes led to novel interventions and a successful reduction of employee slips, trips, and falls events over time, which are broadly generalizable.

Engagement and Bundle Compliance during COVID-19: A Virtual Strategy.

COVID-19 forced industries to change work processes; this was no different for those working to improve patient outcomes in healthcare. Due to competing priorities, many hospitals struggled with the upkeep of hospital-acquired condition (HAC) auditing and engagement. Children's National hospital developed a three-pronged approach for virtual engagement and sustainment of the processes necessary to achieve and maintain goal auditing and bundle compliance in three HACs: unplanned extubation, central line-associated bloodstream infections, and employee staff safety overexertion injuries. Methods: The overall goal was to create a flexible approach to maintaining engagement while relying on virtual communication. Aim: To maintain, without a decrease of more than 20%, the baseline bundle compliance per month for each HAC (unplanned extubation, central line-associated bloodstream infections, and employee staff safety) from March 2020 to March 2021. Our approach to increasing bundle compliance (primary outcome measure) and audits (process measure) included: regular leadership meetings using multiple virtual modalities, improving the audit process, and ensuring fidelity to bundle elements. Results: Qualitatively, we have found that microsystem leaders regularly engage with quality improvement staff and their teams using virtual touchpoints and ongoing communication. We exceeded the goal of maintaining our monthly bundle compliance, and we saw a significant positive change in the rate of audits after COVID-19. Conclusions: In a time of change during a pandemic, increased engagement in HAC work can adapt structure and processes. Our results are generalizable by increasing touchpoints using multiple virtual modalities.

Functional buffering via cell-specific gene expression promotes tissue homeostasis and cancer robustness.

Functional buffering that ensures biological robustness is critical for maintaining tissue homeostasis, organismal survival, and evolution of novelty. However, the mechanism underlying functional buffering, particularly in multicellular organisms, remains largely elusive. Here, we proposed that functional buffering can be mediated via expression of buffering genes in specific cells and tissues, by which we named Cell-specific Expression-BUffering (CEBU). We developed an inference index (C-score) for CEBU by computing C-scores across 684 human cell lines using genome-wide CRISPR screens and transcriptomic RNA-seq. We report that C-score-identified putative buffering gene pairs are enriched for members of the same duplicated gene family, pathway, and protein complex. Furthermore, CEBU is especially prevalent in tissues of low regenerative capacity (e.g., bone and neuronal tissues) and is weakest in highly regenerative blood cells, linking functional buffering to tissue regeneration. Clinically, the buffering capacity enabled by CEBU can help predict patient survival for multiple cancers. Our results suggest CEBU as a potential buffering mechanism contributing to tissue homeostasis and cancer robustness in humans.

Shifting the Paradigm: A Quality Improvement Approach to Proactive Cardiac Arrest Reduction in the Pediatric Cardiac Intensive Care Unit.

INTRODUCTION: Children with cardiac conditions are at higher risk of in-hospital pediatric cardiopulmonary arrest (CA), resulting in significant morbidity and mortality. Despite the elevated risk, proactive cardiac arrest prevention programs in the cardiac intensive care unit (CICU) remain underdeveloped. Our team developed a multidisciplinary program centered on developing a quality improvement (QI) bundle for patients at high risk of CA. METHODS: This project occurred in a 26-bed pediatric CICU of a tertiary care children's hospital. Statistical process control methodology tracked changes in CA rates over time. The global aim was to reduce CICU mortality; the smart aim was to reduce the CA rate by 50% over 12 months. Interprofessional development and implementation of a QI bundle included visual cues to identify high-risk patients, risk mitigation strategies, a new rounding paradigm, and defined escalation algorithms. Additionally, weekly event and long-term data reviews, arrest debriefs, and weekly unit-wide dissemination of key findings supported a culture change. RESULTS: After bundle implementation, CA rates decreased by 68% compared to baseline and 45% from the historical baseline. Major complications decreased from 17.1% to 12.6% (P < 0.001) and mortality decreased from 5.7% to 5.0% (P = 0.048). These results were sustained for 30 months. CONCLUSIONS: Cardiac arrest is a modifiable, rather than inevitable, metric in the CICU. Reduction is achievable through the interprofessional implementation of bundled interventions targeting proactive CA prevention. Once incorporated into widespread efforts to engage multidisciplinary CICU stakeholders, these patient-focused interventions resulted in sustained improvement.

Association Between Socioeconomic Status and In Utero Fetal Brain Development.

Importance: Children raised in settings with lower parental socioeconomic status are at increased risk for neuropsychological disorders. However, to date, the association between socioeconomic status and fetal brain development remains poorly understood. Objective: To determine the association between parental socioeconomic status and in vivo fetal brain growth and cerebral cortical development using advanced, 3-dimensional fetal magnetic resonance imaging. Design, Setting, and Participants: This cohort study of fetal brain development enrolled 144 healthy pregnant women from 2 low-risk community obstetrical hospitals from 2012 through 2019 in the District of Columbia. Included women had a prenatal history without complications that included recommended screening laboratory and ultrasound studies. Exclusion criteria were multiple gestation pregnancy, known or suspected congenital infection, dysmorphic features of the fetus, and documented chromosomal abnormalities. T2-weighted fetal brain magnetic resonance images were acquired. Each pregnant woman was scanned at up to 2 points in the fetal period. Data were analyzed from June through November 2020. Exposures: Parental education level and occupation status were documented. Main Outcomes and Measures: Regional fetal brain tissue volume (for cortical gray matter, white matter, cerebellum, deep gray matter, and brainstem) and cerebral cortical features (ie, lobe volume, local gyrification index, and sulcal depth) in the frontal, parietal, temporal, and occipital lobes were calculated. Results: Fetal brain magnetic resonance imaging studies were performed among 144 pregnant women (median [interquartile range] age, 32.5 [27.0-36.1] years) with gestational age from 24.0 to 39.4 weeks; 75 fetuses (52.1%) were male, and 69 fetuses (47.9%) were female. Higher parental education level was associated with significantly increased volume in the fetal white matter (mothers: ß, 2.86; 95% CI, 1.26 to 4.45; P = .001; fathers: ß, 2.39; 95% CI, 0.97 to 3.81; P = .001), deep gray matter (mothers: ß, 0.16; 95% CI, 0.002 to 0.32; P = .048; fathers: ß, 0.16; 95% CI, 0.02 to 0.31; P = .02), and brainstem (mothers: ß, 0.06; 95% CI, 0.02 to 0.10; P = .01; fathers: ß, 0.04; 95% CI, 0.004 to 0.08; P = .03). Higher maternal occupation status was associated with significantly increased volume in the fetal white matter (ß, 2.07; 95% CI, 0.88 to 3.26; P = .001), cerebellum (ß, 0.17; 95% CI, 0.04 to 0.29; P = .01), and brainstem (ß, 0.03; 95% CI, 0.001 to 0.07; P = .04), and higher paternal occupation status was associated with significantly increased white matter volume (ß, 1.98; 95% CI, 0.71 to 3.25; P < .01). However, higher socioeconomic status was associated with significantly decreased fetal cortical gray matter volume (mothers: ß, -0.11; 95% CI, -0.18 to -0.03; P = .01; fathers: ß, -0.10; 95% CI, -0.18 to -0.03; P = .01). Higher parental socioeconomic status was associated with increased volumes of 3 brain lobes of white matter: frontal lobe (mothers: ß, 0.07; 95% CI, 0.02 to 0.13; P = .01; fathers: ß, 0.06; 95% CI, 0.01 to 0.11; P = .03), parietal lobe (mothers: ß, 0.07; 95% CI, 0.03 to 0.11; P < .001; fathers: ß, 0.06; 95% CI, 0.03 to 0.10; P = .001), and temporal lobe (mothers: ß, 0.04; 95% CI, 0.02 to 0.07; P < .001; fathers: ß, 0.04; 95% CI, 0.02 to 0.07; P < .001), and maternal SES score was associated with significantly decreased volume in the occipital lobe (ß, 0.02; 95% CI, 0.002 to 0.04; P = .03). Higher parental socioeconomic status was associated with decreased cortical local gyrification index (for example, for the frontal lobe, mothers: ß, -1.1; 95% CI, -1.9 to -0.3; P = .01; fathers: ß, -0.8; 95% CI, -1.6 to -0.1; P = .03) and sulcal depth, except for the frontal lobe (for example, for the parietal lobe, mothers: ß, -9.5; 95% CI, -13.8 to -5.3; P < .001; fathers: ß, -8.7; 95% CI, -13.0 to -4.4; P < .001). Conclusions and Relevance: This cohort study found an association between parental socioeconomic status and altered in vivo fetal neurodevelopment. While being born and raised in a lower socioeconomic status setting is associated with poorer neuropsychological, educational, and socioeconomic outcomes in children, these findings suggest that altered prenatal programming may be associated with these outcomes and that future targeted prenatal interventions may be needed.

Reducing Employee Injury Rates with a Hospital-wide Employee Safety Program.

Introduction: Despite the well-known dangers of working in the healthcare industry, healthcare organizations have historically accepted workplace injuries as business as usual. In 2017, Children's National Hospital began our Employee and Staff Safety program to drive down the employee injury rate and address this disturbing industry trend. Methods: With guidance and support from executive leadership, we created an Employee and Staff Safety program that aligned employee safety work with existing patient safety and quality improvement efforts. Team leads collected and analyzed baseline employee injury data and identified areas of highest injuries. Dedicated subcommittees focused on five specific areas: slips, trips, and falls; sharps injuries; blood and body fluid exposures; verbal and physical violence; and overexertion injuries. Subcommittees established aims, identified key drivers, and brainstormed interventions for tests of change. Results: Because the inception of the Employee and Staff Safety program, Children's National has seen significant reductions in our Days Away Restricted or Transfer (DART) rate. The DART rate shows a sustained 37% reduction since the baseline period of FY16-FY17 (1.48 injuries/200,000 h worked to 0.93 injuries/200,000 h worked). The regression trend shows a significant decrease (38.3%) in DART injuries, from 1.544 to 0.952 over 56 months; P = 0.016. Conclusions: Active leadership support and analyzing data on specific employee harm areas coupled with targeted interventions, helped improve Children's National's DART rate. The Employee and Staff Safety program's success in utilizing patient safety and quality improvement tools creates a generalizable framework for other hospitals to advance their high-reliability journey.

Improving Accuracy and Timeliness of Nursing Documentation of Pediatric Early Warning Scores.

INTRODUCTION: Accurate and timely documentation of pediatric early warning scores (PEWS) by the bedside nurse into the electronic health record (EHR) is important to promote early identification of patients in stages of deterioration. Through the implementation of a PEWS calculator embedded in the EHR, we hope to improve the accuracy of the recorded score and reduce the time between vital sign collection and final documentation in the EHR. METHODS: Identification of the highest PEWS value in the 24 hours before all unplanned transfers or rapid response activations without a transfer occurred between the period November 1, 2013, through December 31, 2016. The accuracy of the calculated cardiac or respiratory subscore based on heart rate or the respiratory rate at the time of PEWS calculation was determined. We tracked the calculation of the time to chart via the difference between nursing documentation of PEWS compared to vital sign collection. Before September 3, 2015, PEWS was calculated mentally by the bedside nurse; afterward, the nurse entered the unique PEWS features into the EHR, and the EHR automatically calculated PEWS. RESULTS: This study evaluated 2,409 PEWS scores, 1,411 before and 998 after initiation of the PEWS calculator. Accuracy before the EHR calculator was 71%, and the median time to document was 55 minutes. Following the implementation of the calculator, no scores were incorrectly calculated too low, and the median time to document was 20 minutes. CONCLUSIONS: Transition to an EHR-based PEWS calculator eliminated inaccurately low PEWS values and reduced time to document.

Apparent Cause Analysis: A Safety Tool.

Causal analysis is a core function of safety programs. Although established protocols exist for conducting root cause analysis for serious safety events, there is limited guidance for apparent cause analysis (ACA) in health care. At our institution, through a novel facilitated ACA approach, we aim to improve safety culture and provide a clear approach to address precursor safety events and near-miss safety events. We define facilitated ACA as limited investigation (scope and duration) of a safety event that resulted in little to no harm. These investigations require fewer resources and focus on preventive strategies. Our facilitated ACA model, with an operational algorithm and structured process, was developed and implemented at our tertiary-care, freestanding, urban pediatric hospital in 2018. Sixty-four ACAs were completed, and 83% were identified with the algorithm. Process measures, including time from event reporting to ACA launch (median 3 days; interquartile range 2-6 days), are tracked. Patient safety consultants averaged 5 hours to complete a facilitated ACA. A median of 3 disciplines or departments participated in each facilitated ACA. Through an iterative process, we implemented a structured process for facilitated ACA, and the model's strength includes (1) right event, (2) right team, (3) right analysis, and (4) right action plans. This novel facilitated ACA model may support organizational cause analysis and improve safety culture with higher-reliability processes.

PRKDC: new biomarker and drug target for checkpoint blockade immunotherapy.

BACKGROUND: Immunological checkpoint blockade is effective in treating various malignancies. Identifying predictive biomarkers to assist patient selection for immunotherapy has become a priority in both clinical and research settings. METHODS: Mutations in patients who responded to immunotherapy were identified through next-generation sequencing. Relationships among protein kinase, DNA-activated, catalytic polypeptide (PRKDC) mutations, mutation load and microsatellite instability (MSI) were analyzed using datasets from The Cancer Genome Atlas. These relationships were validated by conducting an in vitro study and by using tissue samples from 34 patients with gastric cancer. The CT26 animal model was used to evaluate the role of PRKDC as a predictive biomarker and the efficacy of the DNA-PK inhibitor. RESULTS: From the published literature, we found that among patients whose tumors harbored PRKDC mutations, 75%, 53.8%, and 50% of those with lung cancer, melanoma, and renal cell carcinoma, respectively, responded to immunotherapy. Most of these mutations were truncating and located in functional domains or in a destabilizing PRKDC protein structure. Additional analysis showed that a PRKDC mutation was significantly associated with a high mutation load in cervical cancer, colon adenocarcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, gastric adenocarcinoma and endometrial cancer. Patients with gastric cancer or colon cancer harboring PRKDC mutations were also highly associated with MSI-high status. Finally, we found that knockout PRKDC or DNA-PK inhibitor (PRKDC encodes the catalytic subunit of DNA-dependent protein kinase) enhanced the efficacy of the anti-programmed cell death protein one pathway monoclonal antibody in the CT26 animal model. CONCLUSIONS: PRKDC is not only a predictive biomarker but also a drug target for immune checkpoint inhibitors.