March 27, 2020
In This Issue

Research Spotlight:
New Project Will Help Parents Quit Smoking

CPCE In the News:
Venetoclax and Chemo: A 'Step Forward' for Children With r/r AML

CPCE In the News:
Most mass shootings occur closest to hospitals without verification to treat trauma

Upcoming Events

Recent Publications
New Project Will Help Parents Quit Smoking
A new project awarded to CPCE and PolicyLab investigators, along with colleagues at Massachusetts General Hospital (MGH), aims to ensure that parents who smoke tobacco and visit their child’s doctor will receive help to quit smoking.

Smoking cessation benefits parents and children alike, extending the parent’s life expectancy, decreasing the child’s exposure to secondhand smoke, improving families’ financial resources, among other positive outcomes. Parents who smoke are often medically underserved, seeing their child’s pediatrician more than they see their own clinicians.

The eCEASE project (full title: Electronic Pediatric Office Systems to Support Treatment for Parental Tobacco Use) is a two-arm stratified cluster RCT, designed to test the implementation, effectiveness, cost-effectiveness, and sustainability of a tobacco dependence treatment intervention for families with smokers. Eight CHOP primary care practices will participate, with four assigned to each arm: one arm will use an innovative extension of existing electronic health records (iEHR) that will integrate the critical workflow of tobacco cessation services for household members in child healthcare settings plus a community health navigator to help all smoking household members with cessation, even if they are not present at the visit; and the other will be the usual care arm.

eCEASE is funded by the National Cancer Institute and led by Alexander Fiks, MD, MSCE at CHOP and Jonathan Winickoff, MD at MGH. Robert Grundmeier, MD and Brian Jenssen, MD, MSHP are CHOP co-investigators. Tyra Bryant-Stephens, MD will lead the community navigator component of the project. Katya Nekrasova, MPH from CHOP and Emara Nabi, MBBS, MS from MGH will serve as the project coordinators. A DBHi informatics team of Jeritt Thayer, Dean Karavite, MS and Naveen Muthu, MD, will work on developing a patient and clinician facing clinical decision support (CDS) tool integrated with the EHR to help parents quit smoking. The project leverages the Clinical Effort Against Secondhand Smoke (CEASE) intervention developed by Dr. Winickoff as well as decision and workflow strategies developed and tested at CHOP, which will be implemented to increase the impact and sustainability of CEASE.

The study is designed to contribute to the field of implementation science by building upon the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework with concepts and data collection tools from the Consolidated Framework for Implementation Research (CFIR). This integrated tool will be used for both data collection and to improve implementation processes and sustainability in each practice. This combination of frameworks has not been widely studied in the context of child healthcare.

The study will also estimate the cost per quit of intervention arm relative to usual care to help accountable care organizations (ACOs), health systems, and payors understand the return on investment and support implementation and sustainability.
Venetoclax and Chemo: A 'Step Forward' for Children with r/r AML

In a study published in The Lancet Oncology, researchers outside of CHOP tested the addition of targeted therapy venetoclax to high-dose chemotherapy in pediatric patients with relapsed or refractory acute myeloid leukemia (AML). Richard Aplenc, MD, PhD, in an accompanying commentary, praised the novelty and potential impact of the phase 1 study, which found that the combination therapy was well-tolerated and active. “This new study is notable for several reasons,” Dr. Aplenc wrote. “First, it is not only the first peer-reviewed publication evaluating the efficacy of venetoclax in a paediatric population, but also the first evaluation of the combination of venetoclax with intensive acute myeloid leukaemia chemotherapy. Thus, in addition to their implications for children, these results are also relevant for the much larger group of adults with acute myeloid leukaemia who are fit for intensive therapy.”
 
Most mass shootings occur closest to hospitals without verification to treat trauma

A CHOP team analyzed data on mass shootings in the United States from 2019, and found that the nearest hospital to more than 70% were non-trauma centers. They further found that more than half of mass shooting events were more than 10 miles from a pediatric trauma center. This is problematic because “the large number of serious injuries caused by mass shootings requires coordinated, high-level initial care, which is most commonly found in a trauma center,” said Sage Myers, MD, MSCE in a CHOP press release. "Yet in the vast majority of events we studied, a non-trauma center was the closest hospital and thus was likely the primary patient-transport destination. Given that mass shootings are unfortunately commonplace, all hospitals - regardless of trauma center status - should expect and prepare for the eventuality of a mass casualty event involving both adults and children." The findings were published in a research letter in JAMA Surgery. Dr. Myers is lead author of the letter; the team also included CPCE team members Scott Lorch, MD, MSCE, Molly Passarella, MS and other CHOP colleagues.

Upcoming Events

CPCE is observing guidance from CHOP and Penn for alternate work arrangements and social distancing due to the novel coronavirus (COVID-19). As a result, the list below looks shorter than usual. Please feel free to contact us with any questions.

Causal Inference Summer Institute
Dates: June 22-25, 2020
Location: Jordan Medical Education Center 5th Floor Law Auditorium, 3400 Civic Center Blvd, Philadelphia
The Center for Causal Inference will host its fourth annual Causal Inference Summer Institute, a four-day, intensive learning experience that will take place at the Perelman School of Medicine, University of Pennsylvania. Each day will offer didactic lectures by experts in the field, discussion of real examples, and hands-on computing sessions. Learn more and register here.
Recent Publications

Following birth, women may access preventative care in adult settings or in pediatric settings with their infants. Experts including Emily Gregory, MD, MHS, Molly Passarella, MS, Alexander Fiks, MD, MSCE, and Scott Lorch, MD, MSCE ran a cohort study linking mother-infant Medicaid claims from 12 states for 2007-2011 births. They found that maternal health risks were associated with increased adult preventative visits, but 38% of dyads had no adult preventive visits in the year following birth. Most dyads had more opportunities for preventative care in pediatric settings than adult settings.

The antibiotic use rate (AUR) has emerged as a potential metric for neonatal antibiotic use, but reported center-level AURs are limited by differences in case mix. Dustin Flannery, DO, MSCE, Sagori Mukhopadhyay, MD, MMSc, Jeffrey Gerber, MD, PhD, MSCE, Molly Passarella, MS, Karen Puopolo, MD, PhD and others ran a retrospective observational study to identify patient characteristics associated with AUR among a large cohort of preterm infants. The results demonstrated that neonatal AURs are influenced by patient-level characteristics besides infection and survival status, including gestational age, sex, and race/ethnicity. 

Sagori Mukhopadhyay, MD, MMSc, Miren Dhudasia, MPH, Karen Puopolo, MD, PhD and their colleagues ran a retrospective study to determine the proportion of well-appearing newborns screened for hypoglycemia, yield of specific screening criteria, and the impact of screening on breastfeeding. Infants screened due to late-preterm birth were most frequently identified as hypoglycemic. The fewest abnormal values occurred among appropriate weight, late-term infants of nondiabetic mothers. Hypoglycemic risk criteria result in screening a large proportion of otherwise well newborns and negatively impact rates of exclusive breastfeeding.

Robert Grundmeier, MD and others conducted a multicenter retrospective cohort study to examine the use, efficacy, and safety of intravenous magnesium sulfate (IVMg). They described the use of IVMg in children with asthma whose emergency department (ED) management was recorded in the Pediatric Emergency Care Applied Research Network (PECARN) Registry. They found that in PECARN Registry EDs, administration of IVMg occurs late in ED treatment, for a minority of the children likely to benefit, with variation between sites. These results suggest that the current clinical role for IVMg in preventing hospitalization is limited and discharge after IVMg administration is likely safe.

Durable ventricular assist devices (VADs) are increasingly used to treat children with heart failure. Studies have shown worse outcomes for children in cardiogenic shock at the time of VAD, but limited data exist on less acutely ill children. Joseph W. Rossano, MD, MS and colleagues describe the association between illness severity and outcomes in this population. They found that children in shock at the time of VAD have poor outcomes. Mechanical ventilation (MV) is associated with increased mortality even in lower acuity Interagency Registry for Mechanical Circulatory Support (INTERMACS) patient profiles.

The recommendation for children with papillary thyroid cancer (PTC) is total thyroidectomy (TT) based on the incidence of bilateral disease. Sogol Mostoufi-Moab, MD, MSCE and her team reviewed the characteristics of bilaterial PTC in a large cohort of children in a retrospective chart review. They found that thirty-eight percent of children diagnosed with PTC demonstrated bilateral disease. Nearly one in four have occult bilateral disease. The features that predicted bilateral disease were multifocality, widely invasive PTC on ultrasound, and the presence of lymphadenopathy. They conclude that TT is the appropriate surgical approach for pediatric patients with PTC.

Genetic alterations in multiple cell signaling pathways are involved in the molecular pathogenesis of thyroid cancer. Oncogene mutation testing and gene-expression profiling are routinely used for the preoperative risk management of adult thyroid nodules. Researchers including Sogol Mostoufi-Moab, MD, MSCE ran a double-blind case-control study to evaluate the potential value of miRNA biomarkers for the classification of pediatric thyroid lesions. Their data suggest that the regulatory miRNA pathways underlying thyroid tumorigenesis are similar in adults and children.

Kristen Feemster, MD, MPH, MSHP and her colleagues ran a Web-based randomized controlled trial of mothers who did not intend to vaccinate their 11- to 14-year old child against human papillomavirus (HPV). They sought to determine whether supplementing a bundled recommendation (for all 11- to 12-year-old platform vaccines) with tailored messaging that addressed one versus all parental concerns improved HPV vaccination intent among mothers. They found that tailored messages addressing all concerns improved HPV vaccination intent and reduced the strength of the main concern more than bundled messages alone, but intent remained low and strength of the main concerns remained high in this vaccine-hesitant population.

A team including Hansel Otero, MD compared quantitative chest CT parameters in perinatally HIV-infected adolescents with and without bronchiolitis obliterans with HIV-uninfected controls and their association with lung function measurements. Their results demonstrated that quantitative chest CT on inspiration is a feasible technique to differentiate HIV-infected adolescents with and without bronchiolitis obliterans. Quantitative CT parameters correlate with spirometric measurements of small-airway disease.

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.