Associations of neighborhood social vulnerability with emergency department visits and readmissions among infants with bronchopulmonary dysplasia.

OBJECTIVES: To characterize associations of the CDC Social Vulnerability Index (SVI) with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD). STUDY DESIGN: Retrospective cohort of 378 preterm infants with BPD from a single center. Multivariable logistic regression quantified associations of SVI with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge. Mediation analysis quantified the extent to which differences in SVI may explain known Black-White disparities in medically attended acute respiratory illness. RESULTS: SVI was associated with medically attended respiratory illness (per SVI standard deviation increment, aOR 1.44, 95% CI: 1.17-1.78). Adjustment for race and ethnicity attenuated the association (aOR 1.27, 95% CI: 0.97-1.64). SVI significantly mediated 31% of the Black-White disparity in ED visits (p = 0.04). CONCLUSIONS: SVI was associated with, and may partially explain racial disparities in, medically attended acute respiratory illness among infants with BPD.

Needs assessment for enhancing pediatric clerkship readiness.

BACKGROUND: Many students report feeling inadequately prepared for their clinical experiences in pediatrics. There is striking variability on how pediatric clinical skills are taught in pre-clerkship curricula. METHODS: We asked students who completed their clerkships in pediatrics, family medicine, surgery, obstetrics-gynecology and internal medicine to rate their pre-clinical training in preparing them for each clerkship, specifically asking about medical knowledge, communication, and physical exam skills. Based on these results, we surveyed pediatric clerkship and clinical skills course directors at North American medical schools to describe the competence students should have in the pediatric physical exam prior to their pediatric clerkship. RESULTS: Close to 1/3 of students reported not feeling adequately prepared for their pediatrics, obstetrics-gynecology, or surgery clerkship. Students felt less prepared to perform pediatric physical exam skills compared to physical exam skills in all other clerkships. Pediatric clerkship directors and clinical skills course directors felt students should have knowledge of and some ability to perform a wide spectrum of physical exam skills on children. There were no differences between the two groups except that clinical skills educators identified a slightly higher expected competence for development assessment skills compared to pediatric clerkship directors. CONCLUSIONS: As medical schools undergo cycles of curricular reform, it may be beneficial to integrate more pre-clerkship exposure to pediatric topics and skills. Further exploration and collaboration establishing how and when to incorporate this learning could serve as a starting point for curricular improvements, with evaluation of effects on student experience and performance. A challenge is identifying infants and children for physical exam skills practice.

Approaches to Interdisciplinary Care for Infants with Severe Bronchopulmonary Dysplasia: A Survey of the Bronchopulmonary Dysplasia Collaborative.

OBJECTIVE: Bronchopulmonary dysplasia (BPD) remains the most common late morbidity for extremely premature infants. Care of infants with BPD requires a longitudinal approach from the neonatal intensive care unit to ambulatory care though interdisciplinary programs. Current approaches for the development of optimal programs vary among centers. STUDY DESIGN: We conducted a survey of 18 academic centers that are members of the BPD Collaborative, a consortium of institutions with an established interdisciplinary BPD program. We aimed to characterize the approach, composition, and current practices of the interdisciplinary teams in inpatient and outpatient domains. RESULTS: Variations exist among centers, including composition of the interdisciplinary team, whether the team is the primary or consult service, timing of the first team assessment of the patient, frequency and nature of rounds during the hospitalization, and the timing of ambulatory visits postdischarge. CONCLUSION: Further studies to assess long-term outcomes are needed to optimize interdisciplinary care of infants with severe BPD. KEY POINTS: · Care of infants with BPD requires a longitudinal approach from the NICU to ambulatory care.. · Benefits of interdisciplinary care for children have been observed in other chronic conditions.. · Current approaches for the development of optimal interdisciplinary BPD programs vary among centers..

Factors associated with discontinuation of pulmonary vasodilator therapy in children with bronchopulmonary dysplasia-associated pulmonary hypertension.

OBJECTIVE: To evaluate factors associated with discontinuation of pulmonary vasodilator therapy in bronchopulmonary dysplasia-related pulmonary hypertension (BPD-PH). STUDY DESIGN: Retrospective study of neonatal, echocardiographic, and cardiac catheterization data in 121 infants with BPD-PH discharged on pulmonary vasodilator therapy from 2009-2020 and followed into childhood. RESULT: After median 4.4 years, medications were discontinued in 58%. Those in whom medications were discontinued had fewer days of invasive support, less severe BPD, lower incidence of PDA closure or cardiac catheterization, and higher incidence of fundoplication or tracheostomy decannulation (p < 0.05). On multivariable analysis, likelihood of medication discontinuation was lower with longer period of invasive respiratory support [HR 0.95 (CI:0.91-0.99), p = 0.01] and worse RV dilation on pre-discharge echocardiogram [HR 0.13 (CI:0.03-0.70), p = 0.017]. In those with tracheostomy, likelihood of medication discontinuation was higher with decannulation [HR 10.78 (CI:1.98-58.59), p < 0.001]. CONCLUSION: In BPD-PH, childhood discontinuation of pulmonary vasodilator therapy is associated with markers of disease severity.

The association between diuretic class exposures and enteral electrolyte use in infants developing grade 2 or 3 bronchopulmonary dysplasia in United States children's hospitals.

OBJECTIVE: To evaluate the association between chronic diuretic exposures and enteral electrolyte use in infants developing severe bronchopulmonary dysplasia (sBPD). STUDY DESIGN: Retrospective longitudinal cohort study in infants admitted to United States children's hospitals. We identified diuretic exposures and measured enteral NaCl and KCl use during pre-defined exposure risk-interval days. We used mixed-effects logistic regression to model the association between diuretic exposures and electrolyte use. RESULTS: We identified 442,341 subject-days in 3252 infants. All common diuretic classes and class combinations were associated with increased NaCl and KCl use. Thiazide monotherapy was associated with greater electrolyte use than loop monotherapy. The addition of potassium-sparing diuretics was associated with a limited reduction in KCl use compared to thiazide monotherapy. CONCLUSIONS: Chronic diuretic exposures are associated with increased NaCl and KCl use. Presumptions about the relative impact of different diuretic classes on electrolyte derangements may be inaccurate and require further study.

Loop Diuretics in Severe Bronchopulmonary Dysplasia: Cumulative Use and Associations with Mortality and Age at Discharge.

OBJECTIVES: To measure between-center variation in loop diuretic use in infants developing severe bronchopulmonary dysplasia (BPD) in US children's hospitals, and to compare mortality and age at discharge between infants from low-use centers and infants from high-use centers. STUDY DESIGN: We performed a retrospective cohort study of preterm infants at <32 weeks of gestational age with severe BPD. The primary outcome was cumulative loop diuretic use, defined as the proportion of days with exposure between admission and discharge. Infant characteristics associated with loop diuretic use at P < .10 were included in multivariable models to adjust for center differences in case mix. Hospitals were ranked from lowest to highest in adjusted use and dichotomized into low-use centers and high-use centers. We then compared mortality and postmenstrual age at discharge between the groups through multivariable analyses. RESULTS: We identified 3252 subjects from 43 centers. Significant variation between centers remained despite adjustment for infant characteristics, with use present in an adjusted mean range of 7.3% to 49.4% of days (P < .0001). Mortality did not differ significantly between the 2 groups (aOR, 0.98; 95% CI, 0.62-1.53; P = .92), nor did postmenstrual age at discharge (marginal mean, 47.3 weeks [95% CI, 46.8-47.9 weeks] in the low-use group vs 47.4 weeks [95% CI, 46.9-47.9 weeks] in the high-use group; P = .96). CONCLUSIONS: A marked variation in loop diuretic use for infants developing severe BPD exists among US children's hospitals, without an observed difference in mortality or age at discharge. More research is needed to provide evidence-based guidance for this common exposure.

The Clinical Evaluation of Severe Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia is a common disease of prematurity that presents along a wide spectrum of disease severity. Infants with high severity require prolonged hospitalizations and benefit from multidisciplinary care. We describe our approach to the evaluation of infants with severe bronchopulmonary dysplasia. Important considerations include the phenotypic heterogeneity in clinical presentation that necessitates individualized care, the common presence of comorbidities and importance of a comprehensive multisystem evaluation, and the value of applying a chronic care model that prioritizes long-term respiratory and neurodevelopmental goals. Key features of the history, physical examination, and diagnostic studies are discussed with these considerations in mind.

Ventilation Strategies in Severe Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is an acquired, developmental chronic lung disease that is a consequence of premature birth. In the most severe form of the disease, infants may require prolonged periods of positive pressure ventilation. BPD is a heterogeneous disease with lung mechanics that differ from those in respiratory distress syndrome; strategies to manage the respiratory support in infants with severe BPD should take this into consideration. When caring for these infants, practitioners need to shift from the acute care ventilation strategies that use frequent blood gases and support adjustments designed to minimize exposure to positive pressure. Infants with severe BPD benefit from a chronic care model that uses less frequent ventilator adjustments and provides the level of positive support that will achieve the longer-term goal of ongoing lung growth and repair.

Association of rare non-coding SNVs in the lung-specific FOXF1 enhancer with a mitigation of the lethal ACDMPV phenotype.

Haploinsufficiency of FOXF1 causes alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a lethal neonatal lung developmental disorder. We describe two similar heterozygous CNV deletions involving the FOXF1 enhancer and re-analyze FOXF1 missense mutation, all associated with an unexpectedly mitigated disease phenotype. In one case, the deletion of the maternal allele of the FOXF1 enhancer caused pulmonary hypertension and histopathologically diagnosed MPV without the typical ACD features. In the second case, the deletion of the paternal enhancer resulted in ACDMPV rather than the expected neonatal lethality. In both cases, FOXF1 expression in lung tissue was higher than usually seen or expected in patients with similar deletions, suggesting an increased activity of the remaining allele of the enhancer. Sequencing of these alleles revealed two rare SNVs, rs150502618-A and rs79301423-T, mapping to the partially overlapping binding sites for TFAP2s and CTCF in the core region of the enhancer. Moreover, in a family with three histopathologically-diagnosed ACDMPV siblings whose missense FOXF1 mutation was inherited from the healthy non-mosaic carrier mother, we have identified a rare SNV rs28571077-A within 2-kb of the above-mentioned non-coding SNVs in the FOXF1 enhancer in the mother, that was absent in the affected newborns and 13 unrelated ACDMPV patients with CNV deletions of this genomic region. Based on the low population frequencies of these three variants, their absence in ACDMPV patients, the results of reporter assay, RNAi and EMSA experiments, and in silico predictions, we propose that the described SNVs might have acted on FOXF1 enhancer as hypermorphs.

A Complete Genome Screening Program of Clinical Methicillin-Resistant Staphylococcus aureus Isolates Identifies the Origin and Progression of a Neonatal Intensive Care Unit Outbreak.

Whole-genome sequencing (WGS) of Staphylococcus aureus is increasingly used as part of infection prevention practices. In this study, we established a long-read technology-based WGS screening program of all first-episode methicillin-resistant Staphylococcus aureus (MRSA) blood infections at a major urban hospital. A survey of 132 MRSA genomes assembled from long reads enabled detailed characterization of an outbreak lasting several months of a CC5/ST105/USA100 clone among 18 infants in a neonatal intensive care unit (NICU). Available hospital-wide genome surveillance data traced the origins of the outbreak to three patients admitted to adult wards during a 4-month period preceding the NICU outbreak. The pattern of changes among complete outbreak genomes provided full spatiotemporal resolution of its progression, which was characterized by multiple subtransmissions and likely precipitated by equipment sharing between adults and infants. Compared to other hospital strains, the outbreak strain carried distinct mutations and accessory genetic elements that impacted genes with roles in metabolism, resistance, and persistence. This included a DNA recognition domain recombination in the hsdS gene of a type I restriction modification system that altered DNA methylation. Transcriptome sequencing (RNA-Seq) profiling showed that the (epi)genetic changes in the outbreak clone attenuated agr gene expression and upregulated genes involved in stress response and biofilm formation. Overall, our findings demonstrate the utility of long-read sequencing for hospital surveillance and for characterizing accessory genomic elements that may impact MRSA virulence and persistence.

Preseason Pediatrics: an Interactive Preclinical Curriculum Enhances Knowledge and Skills in Medical Students.

INTRODUCTION: Medical students have limited preclinical exposure to pediatrics. We created an optional preclinical curriculum for first-year medical students called "Preseason Pediatrics" (PSP). This 6-month curriculum teaches pediatric-specific knowledge and clinical skills, consisting of monthly resident-led didactic sessions followed by complementary resident-mentored clinical experiences. METHODS: Participants completed a survey before and after completion of PSP. Knowledge was assessed with multiple-choice questions pertaining to each topic covered in PSP and perceived skills, with a 5-point Likert scale ranging from not at all (1) to extremely (5) for skills taught. Skill maintenance was assessed with a newborn objective structured clinical exam (OSCE) 6 months after PSP completion in 2016. Students beginning their pediatric clerkship also completed a survey, comparing students who did and did not complete PSP. RESULTS: From 2014 to 2017, 135 first-year medical students participated. Percent correct scores on pediatric knowledge increased in 4/5 topics covered, and students perceived increases in their pediatric skills in all course domains. 86.8% (n = 92/106) of students reported feeling more prepared for the pediatric clerkship. 94.3% (n = 100/106) would recommend the PSP experience to other students. Third-year students who participated in PSP reported higher comfort with pediatric patients prior to their clerkship. CONCLUSIONS: PSP is a successful novel preclinical program introducing students to pediatrics. We demonstrated that didactics paired with resident-mentored clinical experiences improved pediatric knowledge, clinical-based skills, and perceived clerkship preparedness. Students may academically and professionally benefit from such earlier exposure to pediatrics.

Influence of Clinical Competency Committee Review Process on Summative Resident Assessment Decisions.

BACKGROUND: Clinical Competency Committees (CCCs) are charged with making summative assessment decisions about residents. OBJECTIVE: We explored how review processes CCC members utilize influence their decisions regarding residents' milestone levels and supervisory roles. METHODS: We conducted a multisite longitudinal prospective observational cohort study at 14 pediatrics residency programs during academic year 2015-2016. Individual CCC members biannually reported characteristics of their review process and Accreditation Council for Graduate Medical Education milestone levels and recommended supervisory role categorizations assigned to residents. Relationships among characteristics of CCC member reviews, mean milestone levels, and supervisory role categorizations were analyzed using mixed-effects linear regression, reported as mean differences with 95% confidence intervals (CIs), and Bayesian mixed-effects ordinal regression, reported as odds ratios (ORs) and 95% credible intervals (CrIs). RESULTS: A total of 155 CCC members participated. Members who provided milestones or other professional development feedback after CCC meetings assigned significantly lower mean milestone levels (mean 1.4 points; CI -2.2 to -0.6; P < .001) and were significantly less likely to recommend supervisory responsibility in any setting (OR = 0.23, CrI 0.05-0.83) compared with CCC members who did not. Members recommended less supervisory responsibility when they reviewed more residents (OR = 0.96, 95% CrI 0.94-0.99) and participated in more review cycles (OR = 0.22, 95% CrI 0.07-0.63). CONCLUSIONS: This study explored the association between characteristics of individual CCC member reviews and their summative assessment decisions about residents. Further study is needed to gain deeper understanding of factors influencing CCC members' summative assessment decisions.

LINE- and Alu-containing genomic instability hotspot at 16q24.1 associated with recurrent and nonrecurrent CNV deletions causative for ACDMPV.

Transposable elements modify human genome by inserting into new loci or by mediating homology-, microhomology-, or homeology-driven DNA recombination or repair, resulting in genomic structural variation. Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a rare lethal neonatal developmental lung disorder caused by point mutations or copy-number variant (CNV) deletions of FOXF1 or its distant tissue-specific enhancer. Eighty-five percent of 45 ACDMPV-causative CNV deletions, of which junctions have been sequenced, had at least one of their two breakpoints located in a retrotransposon, with more than half of them being Alu elements. We describe a novel ∼35 kb-large genomic instability hotspot at 16q24.1, involving two evolutionarily young LINE-1 (L1) elements, L1PA2 and L1PA3, flanking AluY, two AluSx, AluSx1, and AluJr elements. The occurrence of L1s at this location coincided with the branching out of the Homo-Pan-Gorilla clade, and was preceded by the insertion of AluSx, AluSx1, and AluJr. Our data show that, in addition to mediating recurrent CNVs, L1 and Alu retrotransposons can predispose the human genome to formation of variably sized CNVs, both of clinical and evolutionary relevance. Nonetheless, epigenetic or other genomic features of this locus might also contribute to its increased instability.

Thresholds and interpretations: How clinical competency committees identify pediatric residents with performance concerns.

BACKGROUND: Clinical competency committee (CCC) identification of residents with performance concerns is critical for early intervention. METHODS: Program directors and 94 CCC members at 14 pediatric residency programs responded to a written survey prompt asking them to describe how they identify residents with performance concerns. Data was analyzed using thematic analysis. RESULTS: Six themes emerged from analysis and were grouped into two domains. The first domain included four themes, each describing a path through which residents could meet or exceed a concern threshold:1) written comments from rotation assessments are foundational in identifying residents with performance concerns, 2) concerning performance extremes stand out, 3) isolated data points may accumulate to raise concern, and 4) developmental trajectory matters. The second domain focused on how CCC members and program directors interpret data to make decisions about residents with concerns and contained 2 themes: 1) using norm- and/or criterion-referenced interpretation, and 2) assessing the quality of the data that is reviewed. CONCLUSIONS: Identifying residents with performance concerns is important for their education and the care they provide. This study delineates strategies used by CCC members across several programs for identifying these residents, which may be helpful for other CCCs to consider in their efforts.

A Novel In Situ Simulation Intervention Used to Mitigate an Outbreak of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit.

OBJECTIVE: To describe the successful implementation of an in situ simulation program to diagnose and correct latent safety threats in a level 4 neonatal intensive care unit (NICU) to mitigate a methicillin-resistant Staphylococcus aureus (MRSA) outbreak. STUDY DESIGN: An investigational report describes a simulation intervention that occurred during a 4-month MRSA outbreak in a single-center, 46-bed, newly renovated level 4 NICU. The simulation program was developed for all NICU providers in which they were exposed to a 30-minute in situ human simulation intervention that included education, evaluation, and debriefing to resolve perceived or observed latent safety threats. The primary study outcome was improved hand hygiene compliance and an enhanced estimate of the culture of safety during a 6-month period. RESULTS: A total of 99 healthcare providers including physicians, nurses, respiratory therapists, and environmental service workers completed the course. Before the simulation intervention, there were 18 patients colonized or infected with a single MRSA clone; after the intervention, there were no new episodes of colonization or infection. CONCLUSIONS: An in situ, simulation-based intervention can counter threats to patient safety related to workflow and lapses in infection control practices and improve patient outcomes.

Endotracheal tube: friend or foe? Bacteria, the endotracheal tube, and the impact of colonization and infection.

The microbiology of the endotracheal tube culture plays a role in diagnosing a variety of diseases in the newborn intensive care unit, including subglottic stenosis, bronchopulmonary dysplasia, and ventilator-associated pneumonia. Bacterial production of a biofilm that coats the endotracheal tube acts as a reservoir for infection, prevents eradication, and may play a role in the development of subglottic stenosis. The diagnosis of ventilator-associated pneumonia is limited by the CDC definition as well as currently available diagnostic methods. Biomarkers could aid in differentiating colonization from infection, but are not available to most clinicians. The etiology of ventilator-associated pneumonia is often polymicrobial. Failure to differentiate colonization from infection results in unnecessary prescription of antibiotics, which could contribute to antimicrobial resistance. Measures to prevent ventilator-associated pneumonia have been described, primarily in the adult population.

Statewide NICU central-line-associated bloodstream infection rates decline after bundles and checklists.

OBJECTIVE: In 2008, all 18 regional referral NICUs in New York state adopted central-line insertion and maintenance bundles and agreed to use checklists to monitor maintenance-bundle adherence and report checklist use. We sought to confirm whether adopting standardized bundles and using central-line maintenance checklists reduced central-line-associated bloodstream infections (CLABSI). METHODS: This was a prospective cohort study that enrolled all neonates with a central line who were hospitalized in any of 18 NICUs. Each NICU reported CLABSI and central-line utilization data and checklist use. We used χ(2) to compare CLABSI rates in the preintervention (January to December 2007) versus the postintervention (March to December 2009) periods and Poisson regression to model adjusted CLABSI rates. RESULTS: Each study period included more than 55 000 central-line days and more than 200 000 patient-days. CLABSI rates decreased 67% statewide (risk ratio: 0.33 [95% confidence interval: 0.27-0.41]; P < .0005); after adjusting for the altered central-line-associated bloodstream infection definition in 2008, by 40% (risk ratio: 0.60 [95% confidence interval: 0.48-0.75]; P < .0005). A total of 13 of 18 NICUs reported using maintenance checklists for 10% to 100% of central-line days. The checklist-use rate was associated with the CLABSI rate (coefficient: -0.57, P = .04). A total of 10 of 18 NICUs were independent CLABSI rate predictors, ranging from 1 site with greatly reduced risk (incidence rate ratio: 0.04, P < .0005) to 1 site with greatly increased risk (incidence rate ratio: 2.87, P < .0005). CONCLUSIONS: Although standardizing central-line care elements led to a significant statewide decline in NICU CLABSIs, site of care remains an independent risk factor. Using maintenance checklists reduced CLABSIs.

Necrotising enterocolitis: the state of the science.

Necrotizing enterocolitis is the most common gastrointestinal emergency of the neonate, affecting 5-10% of infants, yet the pathogenesis remains unclear. Widely accepted risk factors include prematurity, enteral feeds, bacterial colonization and mucosal injury. How these or other yet identified factors come together to create the classic clinical and pathologic features is the subject of much research. The activation of the cytokine cascade, in part by bacterial ligands, appears to play a key role in mucosal injury. Two mediators that may also contribute are platelet activating factor and intestinal toll-like receptors. Short chain fatty acids, the products of bacterial fermentation of carbohydrates, have been thought to cause mucosal injury. Overgrowth of pathogenic bacteria in the face of a decreased commensal population may play a key role. A current focus of clinical research involves probiotics, enterally fed forms of commsenal bacteria. This may set the stage for a healthier intestinal ecosystem and possibly, decreased risk of NEC.