May 8, 2020
In This Issue

Research Spotlight:
CPCE In the News:
COVID-19 Edition

CPCE In the News:
Pulse Oximetry Overused for Bronchiolitis in Kids

CPCE In the News:
Increased Mortality among Children in Foster Care

CPCE In the News:
Drug prevents severe cardiac events in children undergoing chemotherapy for AML

CPCE In the News:
MRI interpretation of suspected sacroiliitis varies greatly in children

CPCE In the News:
Research reveals early life microbiome development

Upcoming Events

Recent Publications
CPCE In the News: COVID-19 Edition
After a brief hiatus from CPCE E-News, we are back this week with a roundup of how our team has been addressing the COVID-19 pandemic.

A team including Karen Puopolo, MD, PhD, Dustin Flannery, DO, MSCE, Sagori Mukhopadhyay, MD, MMSc, and Jeffrey Gerber, MD, PhD, MSCE is focused on perinatal COVID-19 epidemiology. Dr. Puopolo commented on current recommendations to separate infected mothers from their newborns. “Can babies be infected if the mother is infected at birth? The answer is yes, not commonly, but yes,” she said in a Kaiser Health News story. She is a co-author of the American Academy of Pediatrics guidance for infants born to mothers with COVID-19. As so much is unknown about mother-infant transmission, Dr. Puopolo and her team will use electronic health records and clinical tests to investigate risk of transmission and outcomes in infants impacted by the virus.

Kathleen Chiotos, MD, MSCE, Kevin Downes, MD, and others authored a paper on antiviral usage guidance for children with COVID-19. The article, accepted to the Journal of the Pediatric Infectious Diseases Society, is a report from a panel of physicians and pharmacists from 18 North American institutions. From the available evidence, these scientists concluded that antiviral therapy is unnecessary for the majority of pediatric COVID-19 patients, given the typically mild presentation in this population. After weighing risks and benefits on a case-by-case basis, physicians should consider antivirals for severely ill patients, with remdesivir as the preferred agent. “One thing that we hope was clear from the guidance is that the literature around therapy is changing rapidly — so clinicians should continue to critically review the literature as therapeutic decisions are being considered,” said Dr. Chiotos, who is the paper’s lead author, for clinical information website Healio.

Sarah Wood, MD, MSHP and Nadia Dowshen, MD, MSHP are taking the opportunity to test acceptability and feasibility of video-based telemedicine for adolescent health services. Dr. Dowshen described her experiences providing telemedicine to her predominantly black and Latinx gay and bisexual young men and transgender women patients in an opinion piece for The Philadelphia Inquirer. These patients often miss appointments, but telemedicine offers care providers a chance to meet them where they are. “When we understand the context of people’s lives and their environments, instead of just writing a prescription, we can design treatment plans that fit into patients’ daily routines,” Dr. Dowshen wrote.

David Rubin, MD, MSCE, Gregory Tasian, MD, MSc, MSCE, Jing Huang, PhD and others have developed a model to predict the impacts of weather, population density, and social distancing on the spread of COVID-19 at the county level. This work is housed on PolicyLab’s website and has been featured in PhillyVoice, The Washington Post, The New York Times, and other news sources. The model tracks and projects COVID-19 cases across 260 U.S. counties (211 with active outbreaks), and was updated last week to include multiple scenarios for relaxing social distancing policies.

Meredith Matone, DrPH, MHS was among public health experts who discussed different models for relaxing social distancing in a piece for The New York Times The Upshot section. She advocated for a focus on surveillance as a primary strategy to complement population-based testing strategies. These efforts could identify hotspots which could then be targeted for more focused testing. This strategy is also described in a PolicyLab Policy Review.

Other projects are in development or underway. Susan Coffin, MD, MPH and others in the Division of Infectious Diseases will conduct a descriptive study of COVID-19 in CHOP patients. Brian Fisher, DO, MSCE and others in the ID Division are conducting a risk assessment of COVID-19 infection among employees in the CHOP network. James Guevara, MD, MPH , Marsha Gerdes, PhD , and Katherine Yun, MD, MHS are investigating the impact of COVID-19 on safety net program use among low-income families of children with developmental disabilities. Chen Kenyon, MD, MSHP , Tyra Bryant-Stephens, MD and colleagues are looking at the impact of COVID-19 on children with asthma. Sage Myers, MD, MSCE is leading CHOP’s participation in a multi-center observational study of changes in chest X-rays temporal to the onset of COVID-19 by region.

We look forward to providing updates on these and other projects as they develop.
Pulse Oximetry Overused in Bronchiolitis in Kids

U.S. national guidelines discourage the use of continuous pulse oximetry to measure blood oxygen levels in infants with bronchiolitis who do not require supplemental oxygen. Despite these guidelines, a study led by Christopher Bonafide, MD, MSCE and published in JAMA found continuous pulse oximetry monitoring use in 46% of patients overall, with considerable variation by hospital and by risk condition. The sample included 3,612 patient observations in 33 freestanding children's hospitals, 14 children's hospitals within hospitals, and 9 community hospitals in the Pediatric Research in Inpatient Settings (PRIS) Network from December 1, 2018, through March 31, 2019. Participants included a convenience sample of patients aged 8 weeks through 23 months.

“We were surprised by the huge amount of variation we saw across the hospitals in this study, which shows many institutions are using monitoring unnecessarily as a safety net,” Dr. Bonafide said in a CHOP press release. “This study represents an essential first step in phasing out an overused, low-value care practice that does not improve outcomes, raises healthcare costs, and leads to alarm fatigue among healthcare workers.”

Increased Mortality among Kids in Foster Care

Barbara Chaiyachati, MD, PhD, fellow in child abuse pediatrics, discussed results of a study she conducted with Joanne Wood, MD, MSHP and colleagues which indicates a higher mortality rate for children in foster care vs. children in the general population. Furthermore, the difference in mortality for children in foster care has increased over time. However, “we cannot conclude that foster care is the cause of the increased mortality,” Dr. Chaiyachati told MedicalResearch.com. “Therefore, we should consider other factors that may be impacting this difference in mortality, including the experiences of children prior to foster care and children’s health status when they enter foster care.”

Drug prevents severe cardiac events in children undergoing chemotherapy for AML

A recent study found cardioprotective effects of dexrazoxane in children undergoing chemotherapy for acute myeloid leukemia (AML). Part of the Children’s Oncology Group, the study looked at patients treated with anthracyclines, a class of chemotherapy drug known to have cardiac side effects. Despite evidence for dexrazoxane’s cardioprotective benefits, it is used in less than 5% of pediatric AML patients in the U.S. The study included 1,014 pediatric AML patients, 96 who received dexrazoxane at every anthracycline course, and 918 who had no dexrazoxane exposure. Patients who received dexrazoxane had significantly lower risk for left ventricular systolic dysfunction (LVSD) and a lower treatment-related mortality than those who did not. Both groups had similar 5-year event free survival and overall survival rates.

These results were covered in a CHOP press release and reported in several medical news outlets. “To our knowledge, these data are the first demonstration of a potential survival benefit with dexrazoxane, specifically a reduction in treatment-related mortality," said Kelly D. Getz, PhD, MPH, the study's lead author. "This suggests that dexrazoxane may directly prevent acute, severe cardiac events that contribute to early deaths. Additional research to understand the underlying biology of anthracycline-associated cardiotoxicity and effective interventions will improve both the cardiovascular and oncologic outcomes for children with cancer."

Richard Aplenc, MD, PhD added, “These results have arguably changed the standard of care for pediatric AML treatment.”

MRI interpretation of suspected sacroiliitis varies greatly in children

Magnetic resonance imaging (MRI) is pivotal in the assessment of early sacroilitis in children. Pamela Weiss, MD, MSCE, Timothy Brandon, MPH, and their team published a paper in which they evaluate the agreement between local radiology reports and central imaging reviewers for active inflammation and structural damage at the sacroiliac joints (SIJs). They found substantial variation in the interpretation of inflammatory and structural lesions at the SIJs in children.

“This is important clinically because pediatric rheumatologists base therapeutic decisions on imaging results, among other factors,” Dr. Weiss told Healio Rheumatology. “In our study, local radiology reports indicating active inflammation resulted in treatment changes by the rheumatologist for more than 75% of cases, and almost half of these were interpreted as not consistent with active inflammation by the central review team.”

 “Additional training for both radiologists and rheumatologists, including adult and pediatric providers, about the maturational changes on MRI in the maturing sacroiliac joint may improve the reliability of sacroiliac joint MRI interpretations. This would in turn increase the utility of MRI in management of pediatric spondyloarthritis.”

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Research reveals early life microbiome development

Jeffrey Gerber, MD, PhD, MSCE contributed to a pair of recently published studies that add to our understanding of early life microbiome development. One, published in Nature Microbiology , provides a baseline for how changes in this environment can impact health and disease later in life. Of particular interest is the impact of microbiome development on weight gain. The infants involved in the study will be followed through the first two years of life. Another study, published in Nature , found that breastmilk, even in small amounts, influences the accumulation of viral populations in the infant gut, and provides a protective effect against potentially pathogenic viruses. They studied stool samples from babies born in the United States and Botswana. Babies from Botswana were more likely to have potentially harmful viruses in their stools at 4 months, but the protective effect of breastmilk was evident regardless of location.

Upcoming Events

CPCE is observing guidance from CHOP and Penn for alternate work arrangements and social distancing due to COVID-19. As a result, the list below looks shorter than usual. We're investigating ways to provide remote content and will update this section appropriately. Please feel free to contact us with any questions in the meantime.

Protecting Human Rights During the COVID-19 Pandemic
Date: May 13, 2020
Time: 12:30 pm
Part of the Drexel University Dornsife School of Public Health webinar series Emerging Issues in the Coronavirus Pandemic, this webinar will focus on public health advocacy seeking to protect populations and communities most left behind. Register here.

New Approaches to the Diagnosis of SARS-CoV-2 Infection - Update on Laboratory Diagnosis of COVID-19
Date: May 19, 2020
Time: 4:00 - 5:00 pm
Part of the Drexel University Dornsife School of Public Health webinar series Emerging Issues in the Coronavirus Pandemic, this webinar will feature panelists Debra L. Powell, M.D., M.S., FIDSA, Chief, Section of Infectious Diseases, Medical Director for Infection Prevention at Tower Health and Alan T. Evangelista, PhD, D(ABMM), Director, Microbiology and Virology, St. Christopher's Hospital for Children. Register here.

COVID-19 and Beyond: Fundamental Issues Impacting Primary Care
Date: May 28, 2020
Time: 1:00 - 2:00 pm
Part of the Primary Care Development Corporation's (PCDC) COVID-19 webinar series, this session will review the core issues that continue to affect primary care’s ability to play its fundamental role in providing the first contact, coordinated, comprehensive and continuous care critical to improving the health of communities in the COVID-19 pandemic response and beyond. For more information, click here.
Recent Publications

The standard of care for pediatric differentiated thyroid cancer (DTC), the most common childhood thyroid malignancy, is total thyroidectomy followed by radioactive iodine (RAI) treatment when indicated. Pediatric oncologists are increasingly involved in the evaluation of thyroid nodules in childhood cancer survivors and in the management of advanced thyroid cancer. In 2015, the American Thyroid Association published management guidelines for children with DTC. Sogol Mostoufi-Moab, MD, MSCE and her team provide an overview of the current standard of care and highlight available targeted therapies for progressive or RAI refractory DTC.

Diana Montoya-Williams, MD, Molly Passarella, and Scott Lorch, MD, MSCE sought to evaluate the effect of paid family leave in California on statewide rates of preterm birth, low birthweight, post neonatal mortality, and overall infant mortality, using live birth and death certificates from all in-hospital deliveries in California, Missouri, and Pennsylvania from 1999 to 2008. They found that implementation of paid family leave policies in California was associated with a 12 percent reduction in postneonatal mortality after adjusting for maternal and neonatal factors.

Scott Lorch, MD, MSCE and Robert Grundmeier, MD were part of a team that performed a 3-year retrospective cross sectional study to test the hypotheses that minority children with long-bone fractures are less likely to (1) receive analgesics, (2) receive opioid analgesics, and (3) achieve pain reduction. They found differences in process and outcome measures by race and ethnicity in the emergency department management of pain among children with long-bone fractures. Although minority children are more likely to receive analgesics and achieve >2-point reduction in pain, they are less likely to receive opioids and achieve optimal pain reduction.

Although acute decompensated heart failure (ADHF) is a highly morbid condition among adults; little is known about outcomes in children. Joseph W. Rossano, MD, MS and colleagues analyzed the Pediatric Cardiac Critical Care Consortium registry to determine the epidemiology, contemporary treatments, and predictors of mortality in critically ill children with ADHF. Their results showed that ADHF in children is characterized by comorbidities, high mortality rates, and frequent readmission, especially among patients with congenital heart disease (CHD).

Sepsis is the leading cause of infectious morbidity and mortality among hospitalized neonates. In high-resource pediatric and adult intensive care units (ICUs), use of aqueous chlorhexidine (CHG) solution has been associated with reduced risk of bloodstream infections (BSI). Susan Coffin, MD, MPH and her team assessed the impact of bathing of neonates with 2% CHG on BSI, suspected sepsis, and mortality in a low-income country neonatal care unit. In their single center study, CHG bathing at admission was associated with a reduced risk of BSI due to a pathogenic organism after adjusting for potential confounding.

Recent studies have demonstrated successful transcatheter patent ductus arteriosus (TC-PDA) closure in small infants. LPA stenosis and aortic coarctation have been seen after TC-PDA, but it is not clear whether device-related left pulmonary artery (LPA)/aortic obstruction persists. Researchers including Michael O’Byrne, MD, MSCE and Andrew C. Glatz, MD, MSCE ran a single-center retrospective study to evaluate short- and middle-term outcomes after TC-PDA closure in small infants, specifically device-related LPA stenosis and aortic coarctation, risk factors, and changes over time. Their results showed that TC-PDA in small infants is effective, without significant complications. Device-related LPA/aortic obstruction can improve with time/growth.

Pamela Weiss, MD, MSCE co-authored an overview of juvenile spondyloarthritis and important differences in the classification criteria, clinical presentation, outcomes, and pathology in juvenile versus adult-onset disease. MRI and ultrasonography are increasingly relied on for the assessment of adult-onset disease activity and change over time in the pediatric population. The unique features of the maturing axial and peripheral skeleton are described for each modality, as they are key to understand for accurate interpretation of pathology in the pediatric population.

Prediabetes awareness in adults has been associated with improved weight management. Whether youth with prediabetes diagnosis experience similar improvements is unknown. Mary Ellen Vajravelu, MD, MSHP, Sandra Amaral, MD, MHS and their colleagues ran a retrospective cohort study to investigate the association between prediabetes identification and body mass index trajectory in overweight and obese adolescents. Their results showed that BMI Z-score trajectory improved more among youth with prediabetes-range HbA1c but also stabilized in screened youth overall.


About CPCE

We are a pediatric research center dedicated to discovering and sharing knowledge about best practices in pediatric care by facilitating, organizing and centralizing the performance of clinical effectiveness research -- research aimed at understanding the best ways to prevent, diagnose and treat diseases in children. CPCE’s multidisciplinary team conducts research on a diverse range of clinical effectiveness topics.

CPCE E-News is edited by Holly Burnside. Please feel free to contact us with questions or feedback.