November 22, 2019
In This Issue

Research Spotlight: Disparities in Premature Births

CPCE In the News:
Antifungals Go Head-to-Head in Pediatric Leukemia Trial 

CPCE In the News:
Teens and Suicide

Upcoming Events

Recent Publications
Disparities in Premature Births
In the second of our two-part series in honor of Prematurity Awareness Month, we are highlighting work by Heather Burris, MD, MPH and colleagues to identify causes of and eventually develop strategies to reduce racial and ethnic disparities in premature births. 

Earlier this year, Dr. Burris and colleagues including Scott Lorch, MD, MSCE published an article in which they described the contributions of environmental factors to the racial disparities of preterm births. At the micro level, environmental exposures involve some element of individual choice, such as diet and smoking. At the macro level, environmental exposures may be physical in nature, such as air and water pollution, or social, such as neighborhood violence, and tend to result from long-standing inequities in the U.S. They suggest that interactions of physical and social environmental exposures, while complex, explain much of the racial disparity in preterm births in the US. Future study of this relationship will require collaboration between perinatal and environmental scientists, social scientists, biostatisticians, epidemiologists, and public health professionals. 

A recent review article outlined the promise and pitfalls of precision medicine for resolving racial disparities in preterm birth. Analysis of the genome, epigenome, metabolome, and microbiome has generated interest in determining whether these biomarkers can help explain racial disparities. The primary pitfall of this approach is the assumption that race is a genetic construct, rather than a social construct, and therefore cannot be modified. Thus, while applying genetics to the social construct of race is problematic, other biomarkers such as the epigenome or metabolome may be on the causal pathway of race and preterm births. Dr. Burris and her colleagues recommend methodological strategies to reduce confounding and bias and improve these studies’ ability to explain racial differences in preterm births. 

Earlier this month, the March of Dimes released its annual report card of preterm birth rates by U.S. state. Dr. Burris commented on these statistics for a news source based in Louisiana, which has one of the highest preterm birth rates. "There are many underlying processes that can lead to preterm birth," she said. "When you look further, the social and environmental factors that women and girls face are the driving factors. We can say that because there are large economic and racial disparities in preterm birth." Meanwhile, Pennsylvania, New Jersey, and Delaware all earned C+ grades on the report card.

Review a larger selection of peer reviewed publications by Dr. Burris here.

Also, in case you missed it, our previous issue described assessment and management of infections in newborns. A new study, described below under Recent Publications, assessed the impact of a Quality Improvement initiative to improve antibiotic stewardship in NICUs.
Antifungals Go Head-to-Head in Pediatric Leukemia Trial

In a study published in JAMA, Brian Fisher, DO, MSCE and colleagues compared caspofungin to fluconazole as antifungal prophylaxis for children and young adults with acute myeloid leukemia (AML). Young AML patients are subjected to prolonged and repeated periods of severe neutropenia while undergoing chemotherapy, putting them at significant risk for invasive fungal diseases. Infections are challenging to treat and can delay anti-leukemic therapy, Dr. Fisher told MedPage Today. Among more than 500 patients in a randomized trial, the incidence of probable or confirmed invasive fungal disease at 5 months was 3.1% in those patients on caspofungin vs. 7.2% in those on fluconazole. The overall reduction appeared to be driven by a lower incidence of invasive aspergillosis in the caspofungin patients. "Those are the types of infections that we would like to prevent because invasive aspergillosis is an invasive mold infection that has significant morbidity, mortality, and probably more morbidity and mortality than, say, yeast infections like invasive candidiasis," Dr. Fisher continued. "The fact that we reduced all invasive fungal disease, and probably more specifically invasive aspergillosis, by giving caspofungin -- without an increase in toxicity -- is to me a positive sign that this is a very reasonable intervention to consider for this specific patient population that sustains long periods of vulnerability with neutropenia."

Teens and Suicide

Stephanie Doupnik, MD, MSHP wrote a moving piece for Vox “The Highlight,” in which she shares her personal experience caring for teens with suicidal ideation, and describes a recent qualitative study published in Hospital Pediatrics. Dr. Doupnik, along with Diana Worsley, MPH and colleagues, conducted semistructured interviews with 27 teens awaiting transfer from the emergency department to inpatient psychiatric treatment after suicide attempt. While suicidal events are triggered by complex and varied circumstances, some themes emerged from the interviews, including an appreciation for a supportive clinical environment and information about what to expect, as well as worry or discomfort about repeated inquiries from the clinical team and about transition to a new healthcare team or back home. "This very real concern highlights how important it is for teens to have a supportive community around them as they recover from a mental health crisis," Dr. Doupnik wrote.

Upcoming Events

Behavioral Economics & Tobacco Control: Pediatrician Message Framing to Help Parents Quit Smoking
Date: TODAY, November 22, 2019
Time: 12:00 - 1:00 pm
Location: Roberts Center, 11th Floor, 11-110
Brian Jenssen, MD, MSHP will present a CPCE/PolicyLab Work-in-Progress session.

Research Data Management Conference
Date: December 5, 2019
Time: 9:00 am - 5:00 pm
Location: Rockefeller University, Welch Hall, 1230 York Ave, New York, NY 
Research Data Management (RDM) is a trending topic within the academic research community. In order to facilitate RDM scholarship, Rockefeller University, Weill-Cornell Medicine and Elsevier are collaborating to offer a symposium focused on RDM in academic institutions. Learn more and register here.

Community-Driven Research Day
Date: December 9, 2019
Time: 9:00 am - 12:00 pm
Location: Thomas Jefferson University, Eakins Lounge, 1020 Locust St., Philadelphia, PA
Community-Driven Research Day (CDRD) encourages collaborations between researchers and community based organizations (CBOs) and community groups who have research questions that they are interested in answering, specifically in ways that address social determinants of health. This year's theme is Partnering for Healthy and Safe Communities. Al Richmond, MSW, Executive Director of the Community-Campus Partnerships for Health, will deliver the keynote address. Poster submissions are due December 2. Non-presenting individuals should register by December 5. Learn more here.
Recent Publications

Although perceived patient demand for antibiotics is known to stimulate unnecessary antibiotic prescribing, Julia Syzmczak, PhD and colleagues sought to identify how clinicians experience this demand and how their perceptions may drive unnecessary prescribing in outpatient settings. They found that clinicians’ most common reason for prescribing non-indicated antibiotics was patient demand. Clinician motivation for prescribing antibiotics when faced with perceived patient demand was tied to three related factors: (i) clinicians want their patients to feel that their clinical visits have value and believe that that is demonstrated by a prescription for antibiotics; (ii) clinicians want to avoid negative repercussions of denying antibiotics, such as damaged reputations, reduced income, emotional exhaustion, and worse relationships with their patients; (iii) clinicians believed that certain patients are impossible to satisfy without an antibiotic prescription. Future stewardship efforts should address these concerns.

Karen Puopolo, MD, PhD and her colleagues sought to determine whether NICU teams who participated in a multicenter quality improvement collaborative increased their compliance with the Centers for Disease Control and Prevention (CDC) core elements for antibiotic stewardship and demonstrated reduced antibiotic use (AU) among newborns. They found that the percentage of NICUs who implemented the CDC core implements increased in each of the 7 domains: leadership, accountability, drug expertise, actions, tracking, reporting, and education. NICU teams participating in this QI collaborative also decreased their AU rate.

Invasive bacterial infections such as bacteremia are common among pediatric recipients of hematopoietic stem cell transplantation (HSCT) and among children with cancer who receive intensive chemotherapy. A panel including Brian Fisher, DO, MSCE sought to develop a clinical practice guideline (CPG) for systematic antibacterial prophylaxis administration in pediatric cancer and HSCT patients. A weak recommendation was made in favor of systematic antibacterial prophylaxis for children receiving intensive chemotherapy for relapsed acute lymphoblastic leukemia (ALL) and acute myeloid leukemia. The panel made a weak recommendation against the use of systematic antibacterial prophylaxis for children receiving induction chemotherapy for ALL, autologous HSCT, and allogeneic HSCT. They made a strong recommendation against its routine use for children whose therapy is not expected to result in prolonged severe neutropenia. In the case of severe neutropenia, prophylaxis with levofloxacin was recommended.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare demyelinating disease, whose rarity makes large randomized-controlled trials challenging despite the need for more studies to determine effective treatment regimens. A team that included Sabrina Gmuca, MD, MSCE, Pamela Weiss, MD, MSCE, and Jeffrey Gerber, MD, PhD, MSCE sought to 1) determine the positive predictive value (PPV) of the ICD-9-CM code for NMO and evaluate case-finding algorithms for identifying patients with NMO/NMOSD and 2) compare the evaluation and treatment of the disease for pediatric versus adult patients. Results showed that the ICD-9 code for NMO is inaccurate for identification of NMO/NMOSD and that using case-finding algorithms increases the PPV. 

Caring for a child with a serious life-threatening illness or SLTI may impact parents’ mental health. A team including Doug Hill, PhD, and Chris Feudtner, MD, PhD, MPH aimed to examine the protective association of social support with anxiety in parents over time following a child’s acute medical event with oncologic and nononcologic serious illnesses. They performed a prospective cohort study with 200 parents of 158 children in the Decision Making in Serious Pediatric Illness study at CHOP. Over a two year period, having higher levels of perceiving social support was associated with lower levels of anxiety in parents of seriously ill children. 

When children are at low risk of bacteremia, sending blood cultures can contribute to unnecessary antibiotic exposure, adverse effects, and increased costs. Charlotte Woods-Hill, MD, Christopher Bonafide, MD, MSCE and colleagues sought to describe practice variation, clinician beliefs, and attitudes surrounding blood culture testing in critically ill children using a cross-sectional electronic survey of PICU clinicians. Their results showed variation in blood culture practices in the PCIU, including fear and reflexive habits as common drivers of ordering blood cultures. Such practices may contribute to over-testing for bacteremia in critically ill children.

With funding from the CPCE Pilot Grant program, Erik Jensen, MD, MSCE and colleagues sought to compare rates of hypoxemia during transpyloric vs. gastric feeding in very preterm infants with severe bronchopulmonary dysplasia via a series of N-of-1 trials. They found a modest increase in hypoxemic events in transpyloric feedings in the 13 infants that completed the trial. Dr. Jensen is a graduate of the Pediatric Hospital Epidemiology and Outcomes Research Training (PHEOT) program managed by CPCE, and is now Assistant Professor of Pediatrics at the Perelman School of Medicine and an attending neonatologist.

CPCE and PolicyLab Core Faculty members Stephanie Mayne, PhD, MHS, Sen Virudachalam, MD, MSHP, and Alex Fiks, MD, MSCE collaborated to examine patterns of unhealthy behavior clustering in a sample of U.S. youth. Behaviors included in the analysis were screen time, overall diet quality, physical activity, fast food consumption, and smoking. Study subjects, from the National Health and Nutrition Examination Survey (NHANES), were grouped into four groups by age range: 2-5, 6-11, 12-15, and 16-19 years. Among 7714 children and adolescents in the analysis, the most prevalent behaviors were excessive screen time and poor diet quality. Unhealthy behavior clustering increased significantly with age, but varied across racial, ethnic and other sociodemographic characteristics.

Based on the premise that neighborhood physical disorder may contribute to adverse pregnancy outcomes by increasing maternal chronic stress, Stephanie Mayne, PhD, MHS and colleagues from Northwestern University used Google Street View to assess physical disorder across Chicago neighborhoods. They then linked these data with geocoded electronic health record data from a large academic women’s hospital. After adjustment for maternal sociodemographics, multiparity, and season of birth, living in a neighborhood with high physical disorder was associated with higher prevalence of preterm birth, small for gestational age, and hypertensive disorder of pregnancy. They recommend future work to disentangle the unique contribution of physical disorder from other characteristics of disadvantaged neighborhoods.

Children with medical complexity and their caregivers deserve to be as protected at home as they are at the hospital. The work of caring for CMC constitutes high-risk work and should be held to similar safety standards. In this Viewpoint, Chris Feudtner, MD, PhD, MPH and former team member Theo Schall, MSW, MBE recommend the following five policy changes to address health outcomes and safety for caregivers of children with medical complexities (CMC): 1) develop clear safety standards for CMC home care work-hour limits, 2) engage and include caregivers in developing work-hours standards, 3) develop systems to measure the quality of care at home, such as a national registry for at-home adverse events, 4) funded policies and programs that address systemic structural problems of a restrictive supply of high-quality professional home care, and 5), clinical teams should have reasonable, informed expectations for parental care.

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.