Publications by authors named "Veronika Shabanova"

73 Publications

Longitudinal Assessment of Global and Regional Left Ventricular Strain in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C).

Pediatr Cardiol 2022 Jan 7. Epub 2022 Jan 7.

Department of Pediatrics, Section of Pediatric Cardiology, Yale School of Medicine, New Haven, CT, USA.

Multisystem inflammatory syndrome in children (MIS-C) is one of the most significant sequela of coronavirus disease 2019 (COVID-19) in children. Emerging literature has described myocardial dysfunction in MIS-C patients using traditional and two-dimensional speckle tracking echocardiography in the acute phase. However, data regarding persistence of subclinical myocardial injury after recovery is limited. We aimed to detect these changes with deformation imaging, hypothesizing that left ventricular global longitudinal (GLS) and circumferential strain (GCS) would remain impaired in the chronic phase despite normalization of ventricular function parameters assessed by two-dimensional echocardiography. A retrospective, single-institution review of 22 patients with MIS-C was performed. Fractional shortening, GLS, and GCS, along with regional longitudinal (RLS) and circumferential strain (RCS) were compared across the acute, subacute, and chronic timepoints (presentation, 14-42, and > 42 days, respectively). Mean GLS improved from - 18.4% in the acute phase to - 20.1% in the chronic phase (p = 0.4). Mean GCS improved from - 19.4% in the acute phase to - 23.5% in the chronic phase (p = 0.03). RCS and RLS were impaired in the acute phase and showed a trend towards recovery by the chronic phase, with the exception of the basal anterolateral segment. In our longitudinal study of MIS-C patients, GLS and GCS were lower in the acute phase, corroborating with left ventricular dysfunction by traditional measures. Additionally, as function globally recovers, GLS and GCS also normalize. However, some regional segments continue to have decreased strain values which may be an important subclinical marker for future adverse events.
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http://dx.doi.org/10.1007/s00246-021-02796-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8739007PMC
January 2022

Clinical decision rule for obtaining peripheral blood cultures in febrile oncology patients.

Pediatr Blood Cancer 2021 Dec 22:e29519. Epub 2021 Dec 22.

Department of Pediatrics, Section of Pediatric Emergency Medicine, Yale School of Medicine, New Haven, CT, USA.

Background: The utility of peripheral blood cultures in pediatric oncology patients presenting with fever is controversial. A recent systematic review showed that about one in 40 bloodstream infections (BSIs) would be missed if only central venous line (CVL) cultures are obtained.

Objective: To derive a clinical decision rule for obtaining peripheral blood cultures in pediatric oncology patients presenting to a pediatric emergency department (PED) with fever and a CVL.

Design/method: A retrospective chart review was performed on pediatric oncology patients referred to the PED for fever while on therapy. Logistic regression with a random intercept was used to determine independent predictors of BSI and generate a prediction model for obtaining peripheral blood cultures. The decision rule was generated from the best performance as measured by a receiver operator curve. Bootstrapping analysis was performed for internal validation.

Results: Predictors that were significant and independently associated with positive peripheral blood cultures included vasopressor support (odds ratio [OR] 16.5, 95% confidence interval [CI]: 2.80-97.71), acute myeloid leukemia (AML) diagnosis (OR 6.9, 95% CI: 1.81-25.98), hypotension (OR 4.0, 95% CI: 1.05-15.17), mucositis (OR 8.2, 95% CI: 2.48-27.01), and maximum temperature in PED ≥39°C (OR 6.6, 95% CI: 2.36-18.20). The area under the curve (AUC) for this model was 0.90 (95% CI: 0.82-0.97) in the derivation cohort and 0.90 (95% CI: 0.81-0.98) after the internal validation.

Conclusions: We derived a clinical prediction model for deciding when to obtain peripheral blood cultures in febrile oncology patients with CVLs on active therapy. Future studies should focus on prospective and external validation of this diagnostic prediction tool.
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http://dx.doi.org/10.1002/pbc.29519DOI Listing
December 2021

North American biliary stricture management strategies in children post liver transplant: multicenter analysis from the SPLIT Registry.

Liver Transpl 2021 Nov 27. Epub 2021 Nov 27.

Hillman Center for Pediatric Transplantation, Children's Hospital of Pittsburgh, Pittsburgh, PA, USA.

Background: Biliary strictures affect 4-12% of pediatric liver transplants (P-LT). Biliary strictures can contribute to graft loss if left untreated, however there remains no consensus on the best course of treatment. Study objectives included analyses of outcomes associated with biliary stricture management strategies via PTC, ERCP or surgery.

Methods: We identified P-LT recipients (2011-2016) with biliary strictures from the Society of Pediatric Liver Transplantation (SPLIT) registry and retrieved imaging, procedural and operative reports from individual centers. Sub-analyses were performed to specifically evaluate PTC and ERCP for "Optimal Biliary Outcome" (OBO), defined as survival with stricture resolution without recurrence or surgery.

Results: 113 children with median 3.9 years of follow-up had strictures diagnosed 100 days (IQR 30, 290) post LT; 81% were isolated anastomotic strictures. Stricture resolution was achieved in 92% within 101 days, more frequently with isolated anastomotic strictures (96%). 20% of strictures recurred, more commonly in association with hepatic artery thrombosis (32%). Patient and graft survival at 1- and 3-years were 99%, 98% and 94%, 92% respectively. In a subgroup analysis of 79 patients with extrahepatic strictures managed by PTC/ERCP: 59% achieved OBO following a median 4 PTC, and 75% following a median 3 ERCP (P=0.0003). Among patients with OBO, those with ERCP had longer time intervals between successive procedures (41, 47, 54, 62, 71 days) than for PTC (27, 31, 36, 41, 48 days; P=0.0006).

Conclusions: Allograft salvage was successful across all interventions. Stricture resolution was achieved in 92%, with 20% risk of recurrence. Resolution without recurrence was highest in patients with isolated anastomotic strictures and without HAT.
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http://dx.doi.org/10.1002/lt.26379DOI Listing
November 2021

Preterm birth among Pacific Islander women and related perinatal outcomes: a scoping review protocol.

BMJ Open 2021 11 2;11(11):e050483. Epub 2021 Nov 2.

Department of Chronic Disease Epidemiology, Yale University School of Public Health, New Haven, Connecticut, USA

Introduction: Infants born alive <37 weeks are classified as premature. The global estimate of preterm birth in 2014 was 10.6%, and it is the leading cause of death of children under the age of 5 years. Preterm birth disproportionately affects women of minority populations, yet knowledge about the incidence and associated outcomes among Pacific Islanders is limited. The objectives of this scoping review are to identify studies that describe risk factors, maternal-child health outcomes and existing interventions to prevent preterm birth among Pacific Islanders, and to summarise the barriers and facilitators to decrease the burden.

Methods And Analysis: We will follow the Joanna Briggs Institute Manual for Evidence Synthesis for scoping reviews and the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) to conduct this scoping review. The Covidence web application will be used for data management and consensus review. We will search on MEDLINE ALL (Ovid), EMBASE (Ovid), Web of Science Core Collection (as licensed at Yale), the Cochrane Library, CINAHL (EBSCOhost) and two non-indexed regional journals ( and ). Title-abstract and full-text screening of eligible studies will be performed by two authors, and data will be extracted by the first author. Outcomes extracted will be presented using evidence mapping.

Ethics And Dissemination: Findings will drive suggestions for new data collection needed to fill knowledge gaps and improve future study designs to decrease the burden of preterm birth among Pacific Islanders. There are no ethical concerns. This protocol will be disseminated in related peer-reviewed journals.
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http://dx.doi.org/10.1136/bmjopen-2021-050483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565552PMC
November 2021

Group prenatal care and improved birth outcomes: Results from a type 1 hybrid effectiveness-implementation study.

Prev Med 2021 Dec 20;153:106853. Epub 2021 Oct 20.

Department of Social and Behavioral Sciences, Yale School of Public Health, New Haven, CT, United States of America.

To compare birth outcomes for patients receiving Expect With Me (EWM) group prenatal care or individual care only, we conducted a type 1 hybrid effectiveness-implementation trial (Detroit and Nashville, 2014-2016). Participants entered care <24 weeks gestation, had singleton pregnancy, and no prior preterm birth (N = 2402). Mean participant age was 27.1 (SD = 5.77); 49.5% were Black; 15.3% were Latina; 59.7% publicly insured. Average treatment effect of EWM compared to individual care only was estimated using augmented inverse probability weighting (AIPW). This doubly-robust analytic method produces estimates of causal association between treatment and outcome in the absence of randomization. AIPW was effective at creating equivalent groups for potential confounders. Compared to those receiving individual care only, EWM patients did significantly better on three of four primary outcomes: lower risk of infants born preterm (<37 weeks gestation; 6.4% vs. 15.1%, risk ratio (RR) 0.42, 95% Confidence Interval (CI) 0.29, 0.54), low birthweight (<2500 g; 4.3% vs. 11.6%, RR 0.37, 95% CI 0.24, 0.49), and admission to NICU (9.4% vs. 14.6%, RR 0.64, 95% CI 0.49, 0.78). There was no difference in small for gestational age (<10% percentile of weight for gestational age). EWM patients attended a mean of 5.9 group visits (SD = 2.7); 70% attended ≥5 group visits. Post-hoc analyses indicated EWM patients utilizing the integrated information technology platform had lower risk for low birthweight infants (RR 0.47, 95% CI 0.24, 0.86) than non-users. Future research is needed to understand mechanisms by which group prenatal care improves outcomes, best practices for implementation, and health systems savings. Trial registration: ClinicalTrials.govNCT02169024.
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http://dx.doi.org/10.1016/j.ypmed.2021.106853DOI Listing
December 2021

CIDEA expression in SAT from adolescent girls with obesity and unfavorable patterns of abdominal fat distribution.

Obesity (Silver Spring) 2021 Dec 21;29(12):2068-2080. Epub 2021 Oct 21.

Division of Pediatric Endocrinology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.

Objective: This study investigated whether variations in cell death-inducing DNA fragmentation factor alpha subunit-like effector A (CIDEA) mRNA expression and protein levels are modulated by the pattern of abdominal fat distribution in adolescent girls with obesity.

Methods: This study recruited 35 adolescent girls with obesity and characterized their abdominal fat distribution by magnetic resonance imaging. Participants had only a periumbilical/abdominal (n = 14) or a paired abdominal and gluteal subcutaneous adipose tissue (SAT) biopsy (n = 21). CIDEA expression was determined by reverse transcription-polymerase chain reaction, CIDEA protein level by Western blot, and the turnover of adipose lipids and adipocytes by H O labeling. In six girls, a second abdominal SAT biopsy was performed (after ~34.2 months) to explore the weight gain effect on CIDEA expression in abdominal SAT.

Results: CIDEA expression decreased in abdominal SAT from participants with high visceral adipose tissue (VAT)/(VAT+SAT); CIDEA inversely correlated with number of small adipocytes, with the increase in preadipocyte proliferation, and with adipogenesis. A strong inverse correlation was found between CIDEA protein level with the newly synthetized glycerol (r = -0.839, p = 0.0047). Following weight gain, an increase in adipocytes' cell diameter with a decrease in CIDEA expression and RNA-sequencing transcriptomic profile typical of adipocyte dysfunction was observed.

Conclusions: Reduced expression of CIDEA in girls with high VAT/(VAT+SAT) is associated with adipocyte hypertrophy and insulin resistance.
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http://dx.doi.org/10.1002/oby.23295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8612981PMC
December 2021

Colonic Fermentation and Acetate Production in Youth with and without Obesity.

J Nutr 2021 Nov;151(11):3292-3298

Yale University School of Medicine, New Haven, CT, USA.

Background: In the last few years, there has been a growing interest in the role of gut microbiota in the development of obesity and its complications.

Objectives: In this study, we tested the following hypotheses: 1) lean youth and youth with obesity experience a different capability of their gut microbiota to ferment carbohydrates and produce acetate; and 2) colonic acetate may serve as a substrate for hepatic de novo lipogenesis (DNL).

Methods: Nineteen lean youth [mean ± SE BMI (in kg/m2): 21.8 ± 0.521] and 19 youth with obesity (BMI: 35.7 ± 1.66), ages 15-21 y, frequency-matched by age and sex, underwent a fasting 10-h sodium [d3]-acetate intravenous infusion to determine the rate of appearance of acetate (Raacet) into the peripheral circulation before and after an oral dose of 20 g of lactulose. Pre- and post-lactulose Raacet values were determined at a quasi-steady state and changes between groups were compared using a quantile regression model. Acetate-derived hepatic DNL was measured in 11 subjects (6 youth with obesity) and its association with Raacet was assessed using Spearman correlation.

Results: Mean ± SE Raacet was not different before lactulose ingestion between the 2 groups (7.69 ± 1.02 μmol · kg-1 · min-1 in lean youth and 7.40 ± 1.73 μmol · kg-1 · min-1 in youth with obesity, P = 0.343). The increase in mean ± SE Raacet after lactulose ingestion was greater in lean youth than in youth with obesity (14.7 ± 2.33 μmol · kg-1 · min-1 and 9.29 ± 1.44 μmol · kg-1 · min-1, respectively, P = 0.001). DNL correlated with Raacet, calculated as changes from the pre- to the post-lactulose steady state (ρ = 0.621; P = 0.046).

Conclusions: These data suggest that youth with obesity ferment lactulose to a lesser degree than youth without obesity and that colonic acetate serves as a substrate for hepatic DNL.This trial was registered at clinicaltrials.gov as NCT03454828.
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http://dx.doi.org/10.1093/jn/nxab277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8562084PMC
November 2021

Pediatric emergency medicine fellows' milestone evaluations: Do they all meet the targets for graduation?

AEM Educ Train 2021 Jul 1;5(3):e10620. Epub 2021 Jul 1.

Yale University School of Medicine New Haven Connecticut USA.

Background: The ACGME Milestone Project created a competency-based trainee assessment tool. Subcompetencies (SCs) are scored on a 5-point scale; level 4 is recommended for graduation. The 2018 Milestones Report found that across subspecialties, not all graduates attain level 4 for every SC.

Objective: The objective was to describe the number of pediatric emergency medicine (PEM) fellows who achieve ≥ level 4 in all 23 SCs at graduation and identify SCs where level 4 is not achieved and factors predictive of not achieving a level 4.

Methods: This is a multicenter, retrospective cohort study of PEM fellows from 2014 to 2018. Program directors provided milestone reports. Descriptive analysis of SC scores was performed. Subanalyses assessed differences in residency graduation scores, first-year fellowship scores, and the rate of milestone attainment between fellows who did and did not attain ≥ level 4 at graduation.

Results: Data from 392 fellows were obtained. There were no SCs in which all fellows attained ≥ level 4 at graduation; the range of fellows scoring < level 4 per SC was 7% to 39%. A total of 67% of fellows did not attain ≥ level 4 on one or more SC. While some fellows failed to attain ≥ level 4 on up to all 23 SCs, 26% failed to meet level 4 on only one or two. In 19 SCs, residency graduation and/or first year fellow scores were lower for fellows who did not attain ≥ level 4 at graduation compared to those who did (mean difference = 0.74 points). Among 10 SCs, fellows who did not attain ≥ level 4 at graduation had a faster rate of improvement compared to those who did attain ≥ level 4.

Conclusion: In our sample, 67% of PEM fellows did not attain level 4 for one or more of the SCs at graduation. Low scores during residency or early in fellowship may predict difficulty in meeting level 4 by fellowship completion.
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http://dx.doi.org/10.1002/aet2.10620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212389PMC
July 2021

Milestones comparisons from residency to pediatric emergency medicine fellowship: Resetting expectations.

AEM Educ Train 2021 Jul 8;5(3):e10600. Epub 2021 May 8.

Yale University New Haven Connecticut USA.

Background: Pediatric emergency medicine (PEM) fellowships accept trainees who have completed a residency in either emergency medicine (EM) or pediatrics and have adopted 17 subcompetencies with accompanying set of milestones from these two residency programs. This study aims to examine the changes in milestone scores among common subcompetencies from the end of EM or pediatrics residency to early PEM fellowship and evaluates time to reattainment of scores for subcompetencies in which a decline was noted.

Methods: This is a national, retrospective cohort study of trainees enrolled in PEM fellowship programs from July 2014 to June 2018. PEM fellowship program directors voluntarily submitted deidentified milestone reports within the study time frame, including end-of-residency reports. Descriptive analyses of milestone scores between end of residency and PEM fellowship were performed.

Results: Forty-eight U.S. PEM fellowship programs (65%) provided fellowship milestone data on 638 fellows, 218 (34%) of whom also had end-of-residency milestone scores submitted. Of 218 fellows eligible for analysis, 210 (96%) had completed a pediatrics residency and eight (4%) had completed an EM residency. Pediatric-trained fellows had statistically significant decreases in mean milestone scores in all 10 shared subcompetencies. Reattainment of milestone scores across all common subcompetencies for both EM and pediatric-trained PEM fellows occurred by the end of fellowship.

Conclusions: This study demonstrated declines in milestone scores from the end of primary residency training in pediatrics to early PEM fellowship in shared subcompetencies, which may suggest that performance expectations are reset at the beginning of PEM fellowship. Changes in subcompetency milestone anchors to provide subspecialty-specific context may be needed to more accurately define skills acquisition in the residency-to-fellowship transition.
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http://dx.doi.org/10.1002/aet2.10600DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171776PMC
July 2021

Milestone achievements in a national sample of pediatric emergency medicine fellows: impact of primary residency training.

AEM Educ Train 2021 Jul 8;5(3):e10575. Epub 2021 Feb 8.

Pediatrics and Emergency Medicine Yale University School of Medicine New Haven Connecticut USA.

Background: Pediatric emergency medicine (PEM) fellowships recruit trainees from both pediatric and emergency medicine (EM) residencies. The Accreditation Council for Graduate Medical Education (ACGME) defines separate training pathways for each. The 2015 PEM milestones reflect a combination of subcompetencies from the two residencies. This project aims to compare the milestone achievement of PEM fellows based on their primary residency training. We hypothesize that fellows trained in pediatrics achieve PEM milestones at different rates than EM-trained fellows in the ACGME domains of patient care, medical knowledge, systems-based practice, practice-based learning, professionalism, and interpersonal and communication skills.

Methods: This is a multicenter, retrospective cohort study of fellows from a national sample of U.S. PEM fellowship programs. Basic demographic information and deidentified, biannual milestone scores for 23 competencies were collected for fellows training between 2015 and 2018. Subcompetencies are scored on a 5-point milestone scale. Descriptive and multivariable analyses for longitudinal data were performed to compare milestone assessments by primary residency training.

Results: Complete data were obtained for 600 fellows; 95% (570) and 5% (30) completed pediatric and EM residency, respectively. In both year 1 and year 2 of fellowship, the mean milestone scores of EM-trained fellows were statistically higher than pediatrics-trained fellows across the majority of subcompetencies. By the final year of training, there were no statistically significant differences in milestone scores for any of the subcompetencies.

Conclusions: Fellow milestone achievement between groups was not significantly different by graduation. However, fellows entering PEM training from an EM background attained higher scores on the milestones than fellows from a pediatric background in the first year of fellowship.
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http://dx.doi.org/10.1002/aet2.10575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171745PMC
July 2021

A Pilot Study of Youth With Type 1 Diabetes Initiating Use of a Hybrid Closed-Loop System While Receiving a Behavioral Economics Intervention.

Endocr Pract 2021 Jun 15;27(6):545-551. Epub 2020 Dec 15.

Department of Pediatrics, Yale University School of Medicine, One Long Wharf Drive, New Haven, Connecticut.

Objective: Many youth do not use the hybrid closed-loop system for type 1 diabetes effectively. This study evaluated the impact of financial incentives for diabetes-related tasks on use of the 670G hybrid closed-loop system and on glycemia.

Methods: At auto mode initiation and for 16 weeks thereafter, participants received a flat rate for wearing and calibrating the sensor ($1/day), administering at least 3 mealtime insulin boluses per day ($1/day), and uploading ($5/week). Weekly bonuses were given for maintaining at least 70% of the time in auto mode, which were increased for persistent auto mode use from $3/week to a maximum of $13/week. If a participant failed to maintain auto mode for a week, the rewards were reset to baseline. Data from 17 participants aged 15.9 years ± 2.5 years (baseline hemoglobin A1c [HbA1c] 8.6% ± 1.1%) were collected at 6, 12, and 16 weeks. The reinforcers were withdrawn at 16 weeks, with a follow-up assessment at 24 weeks.

Results: With reinforcers, the participants administered an average of at least 3 mealtime insulin boluses per day and wore the sensor over 70% of the time. However, auto mode use waned. HbA1c levels decreased by 0.5% after 6 weeks, and this improvement was maintained at 12 and 16 weeks (P < .05). Upon withdrawal of reinforcers, HbA1c levels increased back to baseline at 24 weeks.

Conclusion: Compensation for diabetes-related tasks was associated with lower HbA1c levels, consistent administration of mealtime insulin boluses, and sustained sensor use. These results support the potential of financial rewards for improving outcomes in youth with type 1 diabetes.
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http://dx.doi.org/10.1016/j.eprac.2020.11.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206518PMC
June 2021

A novel and accurate method for estimating umbilical arterial and venous catheter insertion length.

J Perinatol 2021 07 8;41(7):1633-1637. Epub 2021 Jun 8.

Department of Pediatrics, Yale University School of Medicine, New Haven, CT, USA.

Objective: To develop a novel, rapid, and more accurate model for estimating umbilical arterial (UAC) and venous catheter (UVC) insertion length.

Study Design: We evaluated UACs and UVCs from a retrospective cohort to determine the rate of correct initial positioning based on conventional birth weight-based equations utilized in our neonatal intensive care unit. We then derived new equations, developed the mobile application, UmbiCalc, to simplify implementation of the new equations, and validated their accuracy with prospective utilization.

Results: The conventional equations successfully predicted insertion length in 69% (364 of 524) of UACs and only 36% (194 of 544) of UVCs. Our new model was prospectively applied to 68 UAC and 80 UVC placements with successful initial positioning achieved in 90% [95% CI, 80.2-94.9] and 76% [95% CI, 65.9-84.2], respectively.

Conclusions: Our novel approach more accurately estimates UAC and UVC insertion length.
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http://dx.doi.org/10.1038/s41372-021-01121-7DOI Listing
July 2021

Gender Differences Among Milestone Assessments in a National Sample of Pediatric Emergency Medicine Fellowship Programs.

AEM Educ Train 2021 Jul 3;5(3):e10543. Epub 2020 Nov 3.

and the Yale University School of Medicine New Haven CT USA.

Background: Understanding gender gaps in trainee evaluations is critical because these may ultimately determine the duration of training. Currently, no studies describe the influence of gender on the evaluation of pediatric emergency medicine (PEM) fellows.

Objective: The objective of our study was to compare milestone scores of female versus male PEM fellows.

Methods: This is a multicenter retrospective cohort study of a national sample of PEM fellows from July 2014 to June 2018. Accreditation Council for Medical Education (ACGME) subcompetencies are scored on a 5-point scale and span six domains: patient care (PC), medical knowledge, systems-based practice, practice-based learning and improvement, professionalism, and interpersonal and communication skills (ICS). Summative assessments of the 23 PEM subcompetencies are assigned by each program's clinical competency committee and submitted semiannually for each fellow. Program directors voluntarily provided deidentified ACGME milestone reports. Demographics including sex, program region, and type of residency were collected. Descriptive analysis of milestones was performed for each year of fellowship. Multivariate analyses evaluated the difference in scores by sex for each of the subcompetencies.

Results: Forty-eight geographically diverse programs participated, yielding data for 639 fellows (66% of all PEM fellows nationally); sex was recorded for 604 fellows, of whom 67% were female. When comparing the mean milestone scores in each of the six domains, there were no differences by sex in any year of training. When comparing scores within each of the 23 subcompetencies and correcting the significance level for comparison of multiple milestones, the scores for PC3 and ICS2 were significantly, albeit not meaningfully, higher for females.

Conclusion: In a national sample of PEM fellows, we found no major differences in milestone scores between females and males.
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http://dx.doi.org/10.1002/aet2.10543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166301PMC
July 2021

Use of Pharmacologic Prophylaxis Against Venous Thromboembolism in Hospitalized Injured Children.

J Pediatr Hematol Oncol 2021 Apr 21. Epub 2021 Apr 21.

Division of Hematology CHOC Children's Hospital, Orange, CA Division of Pediatric Surgery Department of General Surgery, Wake Forest School of Medicine, Winston-Salem, NC Section of Critical Care, Department of Pediatrics Children's Wisconsin/Medical College of Wisconsin, Milwaukee, WI Section of General Pediatrics, Department of Pediatrics Section of Pediatric Critical Care, Department of Pediatrics, Yale School of Medicine, New Haven, CT.

Despite a practice management guideline and risk prediction model for venous thromboembolism (VTE), pediatric-specific evidence on pharmacologic prophylaxis is lacking. In a retrospective study, we characterized receipt of prophylaxis and explored its effectiveness in hospitalized injured patients below 18 years old using data from the Trauma Quality Improvement Program. Concordance of receipt of prophylaxis with guideline and predicted risk of VTE was estimated using κ statistic. Effectiveness was explored using cohorts matched based on the risk prediction model. A total of 11,165 (6.2%) of 180,932 patients received prophylaxis. Those who received prophylaxis were more commonly post-pubertal and more severely injured. Receipt of prophylaxis was fairly concordant with the guideline (κ=0.32) and predicted risk of VTE (κ=0.29). Receipt of prophylaxis was associated with higher rates of VTE likely due to confounding by indication. Low molecular weight heparin seemed more effective against VTE than unfractionated heparin (incidence rate ratio: 0.52; 95% confidence interval: 0.36, 0.75), but less effective when received ≥72 hours after admission to the hospital. We showed that hospitalized injured children did not commonly receive prophylaxis. We also showed that prophylaxis may be effective in hospitalized injured children, but it needs to be proven definitively in a randomized clinical trial.
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http://dx.doi.org/10.1097/MPH.0000000000002167DOI Listing
April 2021

Age-Dependent Heterogeneity in the Efficacy of Prophylaxis With Enoxaparin Against Catheter-Associated Thrombosis in Critically Ill Children: A Post Hoc Analysis of a Bayesian Phase 2b Randomized Clinical Trial.

Crit Care Med 2021 04;49(4):e369-e380

Department of Pediatrics, Washington University in St. Louis, St. Louis, MO.

Objectives: We explored the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against central venous catheter-associated deep venous thrombosis in critically ill children.

Design: Post hoc analysis of a Bayesian phase 2b randomized clinical trial.

Setting: Seven PICUs.

Patients: Children less than 18 years old with newly inserted central venous catheter.

Interventions: Enoxaparin started less than 24 hours after insertion of central venous catheter and adjusted to anti-Xa level of 0.2-0.5 international units/mL versus usual care.

Measurements And Main Results: Of 51 children randomized, 24 were infants less than 1 year old. Risk ratios of central venous catheter-associated deep venous thrombosis with prophylaxis with enoxaparin were 0.98 (95% credible interval, 0.37-2.44) in infants and 0.24 (95% credible interval, 0.04-0.82) in older children greater than or equal to 1 year old. Infants and older children achieved anti-Xa level greater than or equal to 0.2 international units/mL at comparable times. While central venous catheter was in situ, endogenous thrombin potential, a measure of thrombin generation, was 223.21 nM.min (95% CI, 8.78-437.64 nM.min) lower in infants. Factor VIII activity, a driver of thrombin generation, was also lower in infants by 45.1% (95% CI, 15.7-74.4%). Median minimum platelet count while central venous catheter was in situ was higher in infants by 39 × 103/mm3 (interquartile range, 17-61 × 103/mm3). Central venous catheter:vein ratio was not statistically different. Prophylaxis with enoxaparin was less efficacious against central venous catheter-associated deep venous thrombosis at lower factor VIII activity and at higher platelet count.

Conclusions: The relatively lesser contribution of thrombin generation on central venous catheter-associated thrombus formation in critically ill infants potentially explains the age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin.
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http://dx.doi.org/10.1097/CCM.0000000000004848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979442PMC
April 2021

A Prospective Study of the Effects of Sex Hormones on Lung Function and Inflammation in Women with Cystic Fibrosis.

Ann Am Thorac Soc 2021 07;18(7):1158-1166

Department of Internal Medicine and.

Epidemiologic studies demonstrate worse outcomes in women with cystic fibrosis (CF) than men. Women are colonized earlier with respiratory pathogens and have increased rates of pulmonary exacerbations after puberty and near ovulation. The etiology of this disparity is unclear, but sex hormones may contribute to these differences. We sought to explore whether natural hormonal fluctuations and hormonal contraception associate with changes in lung function, respiratory symptoms, or inflammatory markers. We prospectively followed women with CF who were not on hormonal contraceptives and reported regular menstrual cycles. We captured study visits at points that corresponded with menses, ovulation, and the luteal phase. A subset of subjects were subsequently placed on a standard oral estrogen/progesterone combination contraceptive pill, ethinyl estradiol/norethindrone (loestrin), and reevaluated. Measurements included lung function, symptom questionnaires, sweat tests, blood for hormone concentrations, and sputum for inflammatory markers, bacterial density, and cytology. Twenty-three women participated in this study. Hormone concentrations were as expected on and off hormonal contraception. At times of peak estrogen (ovulation), there was a significant increase in sputum proinflammatory cytokines (neutrophil-free elastase) and a corresponding pattern of decrease in lung function. Proinflammatory cytokines (IL-8, TNF-α, and neutrophil-free elastase) improved when placed on hormone contraception. Our results show that there are potentially important fluctuations in inflammatory biomarkers in the lungs that correlate with changes in lung function in women with CF. Larger studies evaluating the impact of sex hormones on airway inflammation and immune response are necessary to better understand the clinical impact of these responses.
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http://dx.doi.org/10.1513/AnnalsATS.202008-1064OCDOI Listing
July 2021

Parenting Stress and its Associated Components Prior to an Autism Spectrum Disorder (ASD) Diagnostic Evaluation.

J Autism Dev Disord 2021 Oct 2;51(10):3432-3442. Epub 2021 Jan 2.

Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.

Parents of children with autism spectrum disorder (ASD) show increased levels of parenting stress, but only one study has examined this association before a diagnostic evaluation. We conducted a cross-sectional study of parenting stress in 317 low SES parents with children at-risk for ASD before a diagnostic evaluation. Multiple regression modeling evaluated the associations between parenting stress and parent and child factors. Parenting stress was negatively associated with social support and positively associated with active avoidance coping and parental worry. However, parenting stress was not associated with the child's ASD symptom severity or adaptive functioning, except for self-direction. Findings suggest parenting stress among parents of children at risk of ASD should be assessed prior to diagnosis.
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http://dx.doi.org/10.1007/s10803-020-04804-wDOI Listing
October 2021

Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial.

Crit Care Med 2021 03;49(3):e235-e246

Department of Pediatrics, Washington University in St. Louis, St. Louis, MO.

Objectives: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children.

Design: Bayesian phase 2b randomized clinical trial.

Setting: Seven PICUs.

Patients: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding.

Intervention: Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm).

Measurements And Main Results: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms.

Conclusions: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.
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http://dx.doi.org/10.1097/CCM.0000000000004784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902342PMC
March 2021

Patterns of medication use at end of life by pediatric inpatients with cancer.

Pediatr Blood Cancer 2021 05 11;68(5):e28837. Epub 2020 Dec 11.

Department of Health Policy and Management, Yale School of Public Health, New Haven, Connecticut.

Objective: To describe medication utilization patterns by pediatric inpatients with cancer during their last week of life.

Methods: This retrospective study used data from the Vizient Clinical Database/Resource Manager, a national compilation of clinical and resource use data from over 100 academic medical centers and affiliates. Patients (0-21 years) with malignancy who died during hospitalization (2010-2017) were included (N = 1659). Medications were categorized as opioid, benzodiazepine, gastrointestinal related, chemotherapy, anti-infectives, or vasopressors. Exposure to each group was ascertained for all patients at 1 week and 1 day prior to death. Factors associated with exposure were examined using generalized estimating equations, and summarized using adjusted odds ratios (aORs).

Results: Over the last week of life, there was increased use of opioids (76% to 82%, aOR = 1.55, P < .001) and benzodiazepines (53% to 66%, aOR = 1.36, P = .02), while gastrointestinal-related medication use decreased (92% to 89%, aOR = 0.69, P = .001). Patients had decreased exposure to chemotherapy (10% to 5%, aOR = 0.46, P < .001) and anti-infectives (82% to 73%, aOR = 0.41, P = .002). Vasopressor use increased as death approached (15% to 28%, aOR = 1.67, P = .04). Factors significantly associated with exposure varied with medication category, and included age, race, length of stay, malignancy type, death in the intensive care unit, history of hematopoietic stem cell transplant, and do-not-resuscitate status.

Conclusion: During the week preceding death, administration of symptom management medications increased for children with cancer, but use was not universal. Potentially life-sustaining medications were often continued. Variability in utilization suggests differences in provider/family decision making that warrant further study to develop an evidence-based approach to end-of-life care.
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http://dx.doi.org/10.1002/pbc.28837DOI Listing
May 2021

The association between anti-Müllerian hormone and vitamin 25(OH)D serum levels and polycystic ovarian syndrome in adolescent females.

Reprod Biol Endocrinol 2020 Nov 21;18(1):118. Epub 2020 Nov 21.

Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, 310 Cedar Street, New Haven, CT, 06520-8063, USA.

Background: High anti-Müllerian hormone (AMH) levels and 25-hydroxyvitamin D [25(OH)D] deficiency have been associated with polycystic ovarian syndrome (PCOS) in adult women, and implicated in its pathogenesis. Herein we determined if the level of both AMH and 25(OH)D are altered in adolescent females with clinical features of PCOS.

Methods: This is a cross-sectional study utilizing a retrospective chart review of 128 patients aged 12-20 referred to an academic adolescent gynecology and endocrinology clinic for an evaluation of suspected PCOS. Unadjusted comparisons of AMH and 25(OH)D distributions between subjects with and without PCOS were performed using the Wilcoxon Rank Sum test. Quantile regression was used to compare the median AMH and 25(OH)D between subject groups; adjusting for race, ethnicity, BMI, insurance type, age, and season when bloodwork was performed.

Results: Seventy-four subjects were classified as having PCOS by meeting ≥2 of the three Rotterdam diagnostic criteria, and 47 subjects met only one Rotterdam diagnostic criteria, and were used as the comparative non-PCOS group. There were statistically significant unadjusted differences in median levels of AMH and 25(OH)D. In the adjusted analyses, median AMH was significantly higher in the PCOS group compared to the non-PCOS group (+ 2.39 ng/mL, 95% CI 0.43, 4.35, p = 0.018); 25(OH)D was significantly lower in the PCOS group (- 9.01 ng/mL, 95% CI -14.49, - 3.53 p = 0.001). In our sample, adolescents in both groups had insufficient 25(OH)D level (22 ng/mL) and elevated BMI (32.2 kg/m2).

Conclusions: Adolescents with PCOS display high levels of AMH and low 25(OH)D levels. Since traditional clinical markers of PCOS may be physiologic in adolescents, AMH and 25(OH)D may be used as surrogate markers of PCOS risk in adolescents.
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http://dx.doi.org/10.1186/s12958-020-00676-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679991PMC
November 2020

Bayesian analysis of the epidemiology of bleeding in critically ill children.

J Crit Care 2021 06 29;63:133-138. Epub 2020 Sep 29.

Department of Pediatrics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address:

Purpose: We updated our findings on the epidemiology of clinically relevant bleeding (CRB) in critically ill children. We also determined the concordance of CRB as defined by the International Society of Thrombosis and Haemostasis, i.e., ISTH definition, and characteristics identified by pediatric intensivists in a recent survey, i.e., survey definition.

Methods: In a prospective cohort study, we included children <18 years old who were admitted to the pediatric intensive care unit for >1 day. We followed them daily for bleeding. Bayesian inference was used as the primary analytic tool to incorporate our prior findings.

Results: Using the ISTH definition, the estimated frequency of CRB was 10.0% (95% credible interval, CrI: 7.6%, 12.8%) from 41 of 405 children who had CRB. The estimated frequency from 4 of 12 adolescents >13 years old who received mechanical ventilation or vasopressor support and had CRB was 32.9% (95% CrI: 12.0%, 58.8%). Using the survey definition, the estimated frequency of CRB for the entire cohort was 10.8% (95% CrI: 8.3%, 13.8%). Concordance between definitions for each bleeding event was 0.40 (95% confidence interval: 0.27, 0.52).

Conclusions: Our updated findings highlight the high frequency of CRB regardless of definition used for CRB.
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http://dx.doi.org/10.1016/j.jcrc.2020.09.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005501PMC
June 2021

A Reduced Incretin Effect Mediated by the rs7903146 Variant in the Gene Is an Early Marker of β-Cell Dysfunction in Obese Youth.

Diabetes Care 2020 10 11;43(10):2553-2563. Epub 2020 Aug 11.

Pediatrics Endocrinology and Diabetes Section, Department of Pediatrics, Yale School of Medicine, New Haven, CT

Objective: The risk genotype for the common variant rs7903146 of the transcription factor 7-like-2 () gene has been found to affect the incretin response in healthy and obese adults; however, whether a similar functional defect is also present in obese adolescents remains unexplored. Herein, we examined the functional effect of the rs7903146 variant in the gene on the incretin effect and determined its translational metabolic manifestation by performing deep phenotyping of the incretin system, β-cell function relative to insulin sensitivity, the gastrointestinal-induced glucose disposal (GIGD) in obese youth with normal and impaired glucose tolerance.

Research Design And Methods: Thirty-nine obese adolescents without diabetes (median age 15 [25th, 75th percentile 14, 18] years; BMI 37 [33, 43] kg/m) were genotyped for the rs7903146 variant of and underwent a 3-h oral glucose tolerance test (OGTT) followed by an isoglycemic intravenous glucose infusion (iso-intravenous glucose tolerance test [IVGTT]) to match the plasma glucose concentrations during the OGTT and a hyperglycemic clamp with arginine stimulation. The incretin effect was measured as 100 * (AUC-SR - AUC-SR) / AUC-SR, where AUC-SR = area under the curve of C-peptide secretion rate. Participants were grouped into tertiles according to the percentage incretin effect (high, moderate, and low) to describe their metabolic phenotype.

Results: The presence of T risk allele for was associated with a markedly reduced incretin effect compared with the wild-type genotype (0.3% [-7.2, 14] vs. 37.8% [12.5, 52.4], < 0.002). When the cohort was stratified by incretin effect, the high, moderate, and low incretin effect groups did not differ with respect to anthropometric features, while the low incretin effect group exhibited higher 1-h glucose ( = 0.015) and a reduced disposition index, insulin sensitivity, and insulin clearance compared with the high incretin effect group. GIGD was reduced in the low incretin effect group ( = 0.001). The three groups did not differ with respect to intravenous glucose-induced insulin secretion and arginine response during the hyperglycemic clamp.

Conclusions: A reduced incretin effect and its association with the variant rs7903146 identify an early metabolic phenotype in obese youth without diabetes, featuring a higher plasma glucose peak at 1 h; lower insulin secretion, sensitivity, and clearance; and GIGD.
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http://dx.doi.org/10.2337/dc20-0445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510033PMC
October 2020

Risks of venous thrombosis and bleeding in critically ill adolescents after trauma or major surgery.

J Pediatr Surg 2021 Feb 30;56(2):302-308. Epub 2020 Jun 30.

Section of Critical Care, Department of Pediatrics, Yale School of Medicine, New Haven, CT.

Background: The risks of venous thromboembolism (VTE) and bleeding in critically ill adolescents based on interventions received and anatomic site of trauma or major surgery may identify a cohort eligible for enrollment in a trial of pharmacologic prophylaxis.

Methods: This retrospective cohort study using the Virtual Pediatric Systems database included adolescents admitted to pediatric intensive care units after trauma or major surgery between 2013 and 2017. Mixed effects logistic regression was used to determine the adjusted risks of VTE and bleeding with central venous catheterization (CVC), mechanical ventilation (MV) and anatomic site of trauma or major surgery. The adjusted risks were used to identify the cohort eligible for enrollment.

Measurements And Main Results: VTE developed in 212 (0.8%) of 27,647 adolescents. The adjusted risk of VTE was >2% with CVC and 2 or more of MV and trauma or major surgery to the brain or abdomen. Excluding those with bleeds present on admission or at high risk of bleeding, 375 (1.4%) adolescents would be eligible for enrollment.

Conclusions: VTE is generally uncommon in adolescents after trauma or major surgery. The small proportion of adolescents who are at high risk of VTE and at low risk of bleeding impacts the feasibility of a trial.

Level Of Evidence: Prognostic Study Level II.
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http://dx.doi.org/10.1016/j.jpedsurg.2020.06.037DOI Listing
February 2021

A Low ω-6 to ω-3 PUFA Ratio (n-6:n-3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth.

J Nutr 2020 09;150(9):2314-2321

Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA.

Background: Recent literature suggests that the Western diet's imbalance between high ω-6 (n-6) and low ω-3 (n-3) PUFA intake contributes to fatty liver disease in obese youth.

Objectives: We tested whether 12 wk of a low n-6:n-3 PUFA ratio (4:1) normocaloric diet mitigates fatty liver and whether the patatin-like containing domain phospholipase 3 (PNPLA3) rs738409 variant affects the response.

Methods: In a single-arm unblinded study, obese youth 9-19 y of age with nonalcoholic fatty liver disease were treated with a normocaloric low n-6:n-3 PUFA ratio diet for 12 wk. The primary outcome was change in hepatic fat fraction (HFF%), measured by abdominal MRI. Metabolic parameters included alanine aminotransferase (ALT), lipids, measures of insulin sensitivity, and plasma oxidized linoleic acid metabolites (OXLAMs). Outcomes were also analyzed by PNPLA3 rs738409 genotype. Wilcoxon's signed rank test, the Mann-Whitney U test, and covariance pattern modeling were used.

Results: Twenty obese adolescents (median age: 13.3 y; IQR: 10.5-16.4 y) were enrolled and 17 completed the study. After 12 wk of dietary intervention, HFF% decreased by 25.8% (P = 0.009) despite stable weight. We observed a 34.4% reduction in ALT (P = 0.001), 21.9% reduction in triglycerides (P = 0.046), 3.28% reduction in LDL cholesterol (P = 0.071), and a 26.3% improvement in whole body insulin sensitivity (P = 0.032). The OXLAMs 9-hydroxy-octadecandienoic acid (9-HODE) (P = 0.011), 13-HODE (P = 0.007), and 9-oxo-octadecadienoic acid (9-oxoODE) (P = 0.024) decreased after 12 wk. HFF% declined in both the not-at-risk (CC/CG) and at-risk (GG) PNPLA3 rs738409 genotype groups, with significant (P = 0.016) HFF% reduction in the GG group. Changes in 9-HODE (P = 0.023), 9-oxoODE (P = 0.009), and 13-oxoODE (P = 0.003) differed between the 2 genotype groups over time.

Conclusions: These data suggest that, independently of weight loss, a low n-6:n-3 PUFA diet ameliorates the metabolic phenotype of adolescents with fatty liver disease and that response to this diet is modulated by the PNPLA3 rs738409 genotype.This trial was registered at clinicaltrials.gov as NCT01556113.
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http://dx.doi.org/10.1093/jn/nxaa183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7467848PMC
September 2020

Factors in Early Feeding Practices That May Influence Growth and the Challenges that Arise in Growth Outcomes Research.

Nutrients 2020 Jun 30;12(7). Epub 2020 Jun 30.

Department of Pediatrics, Yale School of Medicine, New Haven, CT 06443, USA.

Growth in preterm infants is associated with improved outcomes during both the initial hospitalization and long-term. A single center investigation evaluated preterm infant in-hospital growth trajectory and how it related to early nutritional practices as a way to identify areas for quality improvement. Infants born <34 weeks' gestational age and with discharge at or prior to 40 weeks' gestational age were included and were divided into quartiles based on their change in weight -score through hospitalization. Early nutritional factors were compared between the lowest and highest growth quartiles. Although the highest growth quartile experienced less days of parenteral nutrition and higher enteral caloric density in the first week, as the data was analyzed, potential statistical pitfalls became apparent. Therefore, the aim of this study was to investigate selection bias and cohort effect related to both the inclusion criteria for this cohort as well as the inherent challenges in comparison of preterm infant growth trajectories by standard fetal growth charts.
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http://dx.doi.org/10.3390/nu12071939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399918PMC
June 2020

Burnout Among Beginning First-Year Students from Three Health Professional Training Programs.

Med Sci Educ 2020 Jun 1;30(2):879-883. Epub 2020 May 1.

Yale School of Medicine, New Haven, CT USA.

The study objective was to learn about burnout prevalence among beginning first-year students from three health professional programs-Advance Practice Registered Nursing (APRN), Medicine, and Physician Associate (PA) training. All first-year students were invited to anonymously complete a survey measuring burnout. Subscales for exhaustion and disengagement together accounted for burnout. Means and frequencies were derived for categorical variables (gender, program, and direct entry from college). Subscales were summarized with means and standard deviations. Analysis of variance and post hoc -tests compared unadjusted differences in means. Based on results, multivariable linear regressions for total burnout and exhaustion examined associations for the independent variables. With a 97% response rate, 70% were female (the APRN program is predominantly female), and 32% began training directly after college. Female students had significantly higher average total burnout and exhaustion than males. APRN and PA students had significantly higher total burnout and exhaustion than MD students. There were no other significant associations. In multivariable linear regressions, APRN students had significantly higher, and PA students had not quite significantly higher, burnout and exhaustion compared with medical students, with no moderation by any other variables. Burnout among first-year students in all three programs was more prevalent than anticipated. Consistent with previous literature, the programs with students who experienced higher burnout used more competitive, multi-tiered grading systems and introduced clinical expectations earlier in training. The implication is that educational leaders should consider effects of competitive grading and early clinical exposure on burnout among beginning health professional students.
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http://dx.doi.org/10.1007/s40670-020-00969-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368543PMC
June 2020

De novo damaging variants associated with congenital heart diseases contribute to the connectome.

Sci Rep 2020 04 27;10(1):7046. Epub 2020 Apr 27.

Departments of Pediatrics, New Haven, CT, USA.

Congenital heart disease (CHD) survivors are at risk for neurodevelopmental disability (NDD), and recent studies identify genes associated with both disorders, suggesting that NDD in CHD survivors may be of genetic origin. Genes contributing to neurogenesis, dendritic development and synaptogenesis organize neural elements into networks known as the connectome. We hypothesized that NDD in CHD may be attributable to genes altering both neural connectivity and cardiac patterning. To assess the contribution of de novo variants (DNVs) in connectome genes, we annotated 229 published NDD genes for connectome status and analyzed data from 3,684 CHD subjects and 1,789 controls for connectome gene mutations. CHD cases had more protein truncating and deleterious missense DNVs among connectome genes compared to controls (OR = 5.08, 95%CI:2.81-9.20, Fisher's exact test P = 6.30E-11). When removing three known syndromic CHD genes, the findings remained significant (OR = 3.69, 95%CI:2.02-6.73, Fisher's exact test P = 1.06E-06). In CHD subjects, the top 12 NDD genes with damaging DNVs that met statistical significance after Bonferroni correction (PTPN11, CHD7, CHD4, KMT2A, NOTCH1, ADNP, SMAD2, KDM5B, NSD2, FOXP1, MED13L, DYRK1A; one-tailed binomial test P ≤ 4.08E-05) contributed to the connectome. These data suggest that NDD in CHD patients may be attributable to genes that alter both cardiac patterning and the connectome.
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http://dx.doi.org/10.1038/s41598-020-63928-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184603PMC
April 2020

Improving Capnography Use for Critically Ill Emergency Patients: An Implementation Study.

J Patient Saf 2022 Jan;18(1):e26-e32

Section of Pediatric Emergency Medicine, Department of Pediatrics and Emergency Medicine, Yale University School of Medicine, New Haven, Connecticut.

Objectives: Capnography has established benefit during intubation and cardiopulmonary resuscitation (CPR). Implementation within emergency departments (EDs) has lagged. We sought to address barriers to improve documented capnography use for patients requiring intubation or CPR.

Methods: A controlled before- and after-implementation study was performed in 2 urban EDs. The control site had an existing policy for capnography use. Interventions for the experimental site included a 5-minute informational video, placement of capnography monitors with a shortened warm-up period in all resuscitation rooms, laminated reminder cards, and feedback during staff meetings. Staff members were surveyed about knowledge before and after the intervention. Records were reviewed for documented capnography use for 3 months before and 6 months after the intervention. Change in documented use at the experimental site was compared with the control site.

Results: At the experimental site, 118 providers participated and 190 records were reviewed; 544 records were reviewed from the control site. There was a significant increase in the proportion of documented capnography use at the experimental site (8% versus 19%, P = 0.04) compared with the control site (64% versus 71%, P = 0.10). However, there was no significant trend over time at the experimental site after the intervention (P = 0.86). Despite high baseline knowledge about capnography, providers had improvements in survey responses regarding indications for intubation and CPR, normal values, and minimum effective values during CPR.

Conclusions: Documented capnography use increased with simple interventions but with no positive trend. Additional work is needed to improve use, including further evaluation of capnography's implementation in the ED.
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http://dx.doi.org/10.1097/PTS.0000000000000683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719501PMC
January 2022

Non-FDA-Reviewed Imported European Formula Use Among Parents in Urban Pediatric Private Practice.

Clin Pediatr (Phila) 2020 06 7;59(6):566-572. Epub 2020 Mar 7.

Yale University, New Haven, CT, USA.

In 2018, the American Academy of Pediatrics warned consumers over the increasing use of imported infant formulas. The purpose of this study was to assess the usage of imported European infant formula among parents in a large urban private practice. An anonymous survey was distributed at well-child appointments to a convenience sample of parents at an urban private pediatric practice from November 2017 to March 2018. Of the 750 eligible respondents, 552 (74%) completed the survey. Of the parents using formula, 20% were using imported European infant formulas. The most commonly used formula was Holle (33%), and 72% were acquired from web-based third-party vendors. Parents chose to use these formulas because they believed that European formulas contained better ingredients. Only 8% of parents received information about European infant formula from their pediatricians. Pediatricians need to be aware of these formulas and their risks to educate families on the use and safety of these formulas.
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http://dx.doi.org/10.1177/0009922820910819DOI Listing
June 2020
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