Chair’s UpdateZora R. Rogers, MD, FAAP

Greetings, and here is hoping that something in this newsletter provides relief from the unre-lenting news about the COVID-19 pandemic.

As you may know the AAP has been in the forefront of discussions regarding many COVID-19 related issues including testing, personal protective equipment and telehealth visits. We have all been receiving informative email updates from the Academy and AAP COVID-19

resources are detailed on the website along with a discussion board for issues you may be facing. The COVID-19 Response Advocacy Report summarizes the AAP’s advocacy activities about this pressing issue at all levels of government and can be accessed here.

This is indeed a time like no other in the prior century, and Spring-Easter-Passover-Ramadan (to name but a few events by which we usually mark the new year) are quieter and more directed inward in 2020. Yet, the lessons of the prior earth changing events: 9-11, World War II, the War to end all Wars (WW1), SARS, AIDS,

Polio, and even the 1918 influenza pandemic are clear -- that by using the best knowledge we have and working together that we will come through. Remind your patients, colleagues, family and yourself of this frequently!

Congratulations to Cynthia Wetmore MD, PhD, FAAP, of Phoenix Children’s Hospital for her election as the next chair of the SOHO Executive Committee! She will assume the position in November 2020.

Despite world events the section continues its work as outlined in the strategic plan. The eleven SOHO/ASPHO policy review groups now have 72 members newly appointed or re-appointed to continue their work. Since this formal process was initiated in January 2014, more than 50 section members have reviewed nearly 200 documents. The new review group term is for 3 years, 2020-2022, and you can view the groups and their current members on the SOHO collaboration site (AAP password and login required). I am so appreciative of all who have worked on this effort! SOHO continues to offer a clear voice for Pediatric Hematology Oncology within the AAP, allowing us to amplify our best science to inform advocacy and payer policy as it effects our patients.

Amongst the items that we have been able to recently provide feedback to include a request for information from the Centers for Medicare and Medicaid Services (also known as CMS) about coordination of care from out-of-state providers for Medicaid recipient children with medically complicated conditions (this addresses an issue in bordering states, and of course when children move states without a new care plan in place). A second was a draft bill to amend Title XIX of the Social Security Act to provide states an option to offer a pediatric all-inclusive-coordinated-care

Section on Hematology/Oncology Newsletter Copyright © 2020 American Academy of Pediatrics

Spring 2020

INSIDE THIS ISSUEChair’s Update � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 1-2

Call for Volunteers: SOHO Education Subcommitte � � � � � � � � 2

Training Fellow Column: Tips for Graduating Pediatric Hematology/Oncology Fellows Searching for their First Job � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 3-4

If you are a member of the SOPT did you know? � � � � � � � � � � 4

Clinical Feature: Hemostatic Mutations in Renal Vein Thrombosis � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 5-6

Hot topics in Hematology and Oncology � � � � � � � � � � � � � � 6-9

Clinical Feature: Clostridioides (Clostridium) Difficile Infection in Children: Highlights of the Updated Guidelines from the IDSA and SHEA � � � 10-11

Tech Tip � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � � 12

“I Am Teaching but are They Learning?”: Maximizing Learning for the Millennial Generation � � � � 12-14

Coding Update: Red Blood Cell Exchange � � � � � � � � � � � 14-15

To Be or Not to Be a Research-Mentor in Pediatrics � � � � 15-17

Join the AAP Mentorship Program � � � � � � � � � � � � � � � � 16-17

Sickle Cell Disease Coalition (SCDC) Updates � � � � � � � � � � 17

SOHO Collaboration Site! � � � � � � � � � � � � � � � � � � � � � � � � � � 17

Welcome to Our New Members � � � � � � � � � � � � � � � � � � � � � 17

For Upcoming Newsletters � � � � � � � � � � � � � � � � � � � � � � � � � � 18

The SOHO Leadership Roster � � � � � � � � � � � � � � � � � � � � � � � 18

AAP Section on

HEMATOLOGY/ONCOLOGYNewsletter

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Chair’s Update Continued from Page 1

(ChiPACC) as part of the Medicaid program. ChiPACC would provide all-inclusive care for children with life-threatening conditions from the time of diagnosis.

Our education subcommittee, led by Mary Jane Hogan, MD, FAAP continues to provide excellent materials for the education of general pediatricians, trainees, parents and ourselves in a variety of formats. Many thanks to the current and former members of the subcommittee for their strong work; and please consider if this is an effort you would like to be part of. There is a call for volunteers below.

Since our last newsletter Vikramjit Kanwar, MD, FAAP published Common Pediatric Cancer Treatments Explained on HealthyChildren.org. Four additional Healthy Children articles authored by section members are in editorial review. In addition, the section’s AAP News Focus on Subspecialty (FOS) article Look for Red Flags that Raise Index of Suspicion for Childhood Cancer, published in September as part of Childhood Cancer Awareness Month, was among the top 5 FOS articles viewed by AAP membership in 2019. As part of sickle cell disease awareness month, Dr. Amber Yates discussed the importance of knowing a patient’s trait status in the AAP Voices blog post, We Didn’t Know This Could Happen and updated two parent focused articles, Sickle Cell Disease: Information for Parents and Can Biracial Children Get Sickle Cell Disease? Additional articles about mentorship, first jobs out of fellowship and educating adult learners in different generations are in this newsletter. We have also begun to review newsletters from other AAP groups to identify content that may be of interest to SOHO members. There are articles in this edition from the Sections on Nephrology and Infectious Diseases.

Further, the revised Clinical Report: “Fertility Preservation for Pediatric and Adolescent Patients with Cancer: Medical and Ethical Considerations” was published in February. An AAP News article with highlights of this report was also published. This report was jointly authored by the Committee on Bioethics, Section on Surgery and SOHO. SOHO member Stephanie Savelli, MD, FAAP, was one of the authors. Four additional reports on, long-term follow-up of pediatric cancer survivors, prevention, diagnosis and treatment of iron deficiency, evaluation of bleeding disorders in child abuse, and sickle cell disease are in various stages of preparation.

So, despite the efforts being devoted to keeping our patients and ourselves healthy and safe in these trying times, SOHO continues to ably carry out its mission: “To educate the pediatric practice community and families regarding pediatric hematology/oncology conditions, make recommendations about health care needs of these patients, and advocate for those who provide and require the care.”

This coming summer and fall will also see an election season unlike any other… fewer stump speeches, no handshakes, and hopefully more earnest policy discussions to honestly address options for solution of issues facing our nation and its children: COVID 19 yes, but also access to health care, fair compensation for those who provide the care, equity in opportunity for education, nutrition, clean air and water, and so many others. In these times as we listen to local, regional, state and national authorities we also need to use our medical and social-science knowledge to make our own individual informed decisions about how best to make a difference and work to make the post pandemic world a better place for our patients, families and ourselves. We have lessons from history that no matter how dire, this too will pass. But let us use the time to determine the world we would like to see, and find a part of the solution to which we can aspire to work. And, be sure to VOTE!

Stay safe!

Sincerely,Zora R. Rogers, MD, FAAPChairperson, Section on Hematology/OncologyZora.Rogers@UTSouthwestern.edu

Call for Volunteers: SOHO Education Subcommittee

The Education Subcommittee is responsible to assist the Executive Committee and the Program Chair in:

• The development of educational programming regarding hematology/oncology for general pediatricians.

• Content review and development regarding hematology/oncology topics for the AAP parent website, http://downloads.aap.org/DOSP/SOHOEducationSubcommitteeDescription.doc

At this time, we are seeking volunteers to serve a three-year term on the Subcommittee. You may access the subcommittee description here (insert link). If you are interested, please submit your CV to Suzanne Kirkwood at skirkwood@aap.org by May 30, 2020.

AAP Section on Hematology/Oncology Newsletter - Spring 2020 Page 3

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Training Fellow Liaison Column: Tips for Graduating Pediatric Hematology/Oncology Fellows Searching for their First Job

Michael Terao, MD, FAAPPediatric Hematology/Oncology Clinical Fellow

St Jude Children’s Research Hospital

Jeffrey D. Hord, MD, FAAPProfessor of Pediatrics, Northeast Ohio Medical University

LOPen Charities and Mawaka Family Chair in Pediatric Hematology OncologyAkron Children’s Hospital

Searching for your first pediatric hematology/oncology attending job is both an exciting and scary time. The tips below provide an evidence-based approach to the job search.

Consider a fourth year of fellowship to receive further training/subspecialization

Recently, more fellows graduating from pediatric hematology/oncology fellowship are taking positions for further training/subspecialization (i.e. bone marrow transplant fellowship, neuro-oncology fellowship) than assistant professor positions1. In 2010, approximately 40% of graduating fellows took assistant professor positions but in 2015 this decreased to approximately 15%1. Conversely, in 2010 approximately 15% of graduating fellows pursued further training/subspecialization but in 2015 this increased to approximately 40%1.

Pediatric hematology/oncology practicing physicians are also becoming more specialized. In 2010, 27% of American Society of Pediatric Hematology/Oncology (ASPHO) members were focused on a specific disease/patient population rather than practicing general pediatric hematology/oncology. This proportion further increased to 40% in 20152. However, it should be noted that the majority of ASPHO members still report working in general pediatric hematology/oncology, so this is still a viable option, although it is becoming less common.

Obtain experience working with advanced practice providers

Advanced practice providers (nurse practitioners, physician assistants) are becoming more involved in providing care to pediatric hematology/oncology patients. In 2015, the majority (85%) of division directors reported advanced practice providers as part of the pediatric hematology/oncology care team2. Advanced practice providers are also providing increasing amounts of clinical care in these teams. In 2012, advanced practice providers accounted for 40% of clinical full-time equivalents (FTE). By 2015, advanced practice providers were providing 47% of the clinical FTE’s2. Given the increasing involvement of advanced practice providers in pediatric hematology/oncology, having experience working with this provider group will make you a more desirable candidate to employers.

Consider a hospitalist job

Hospitalists are also a growing presence in pediatric hematology/oncology. In 2012, 20% of pediatric hematology/oncology programs reported using hospitalists. In 2015, this proportion more than doubled (45% of programs)2. A pediatric hospitalist job often involves working weekends, nights, and holidays but can provide more predictable work schedules3.

Consider a job where the primary responsibility is patient care rather than research

The majority of pediatric hematology/oncology physicians work in positions where the primary responsibility is patient care. In 2016, 58% of ASPHO members reported their primary job responsibility was patient care, and only 22% of ASPHO members reported their primary job responsibility was research2. Similarly, in 2016, 82% of pediatric hematology oncology physicians from the American Medical Association database reported their primary job responsibility was patient care, and only 11% reported their primary job responsibility was research2.

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Training Fellow Liaison Continued from Page 3

Be patient even if your dream job is not available right now

Even if you can’t get your dream job right now, try to be patient and not be discouraged. There is a trend towards a decreased supply of pediatric hematology/oncology fellows over the past few years, which will likely lead to increased job availability in the near future. In 2017, 163 first year pediatric hematology/oncology positions were filled through the match. This then decreased to 153 in 2018, rose slightly to 158 in 2019, but decreased dramatically to 144 in 20204-6.

Consider jobs in various geographic locations

Consider jobs in states where there is a relative lack of pediatric hematology/oncology physicians. The following states have the fewest pediatric hematology/oncology physicians relative to their pediatric populations: Nevada, Oklahoma, Arkansas, Idaho, Utah, Arizona, Mississippi, Kentucky, West Virginia, and New Hampshire2.

What should your patient load and clinical productivity goals be?

When looking at possible jobs, you should ensure your patient load and clinical productivity goals are reasonable.

Pediatric hematology/oncology division directors from 2012 to 2015 reported that a 1.0 physician clinical FTE is equivalent to approximately 12 weeks of inpatient service per year, and 5-7 half day clinic sessions per week2. From 2013 to 2015, pediatric hematology/oncology division directors reported they had approximately 15-20 new cancer patients every year for each 1.0 physician clinical FTE2. From 2012 to 2015, pediatric hematology/oncology programs reported the median work relative value unit (RVU) goal was approximately 3,100 to 3,500 per year for a 100% clinical pediatric hematology/oncology physician2.*

*Please keep in mind that the data provided above is for 1.0 clinical full time equivalent (FTE). If your clinical FTE is less than 1.0, you should adjust the numbers listed above.

References:

1. Leavey PJ, Hilden JM, Matthews D, Dandoy C, Badawy SM, Shah M, Wayne AS, Hord J, of Pediatric Hematology/Oncology Workforce Advisory Taskforce AS. The American Society of Pediatric Hematology/oncology workforce assessment: Part 2—implications for fellowship training. Pediatr Blood Cancer , 2018 65: e26765.

2. Hord J, Shah M, Badawy SM, Matthews D, Hilden J, Wayne AS, Salsberg E, Leavey PS, of Pediatric Hematology/Oncology Workforce Advisory Taskforce AS. The American Society of Pediatric Hematology/oncology workforce assessment: Part 1—current state of the workforce. Pediatr Blood Cancer , 2018 65: e26780.

3. Ahle S. Pediatric Hematology/Oncology: A Small Specialty Experiencing Big Changes - ASH Clinical News [Internet]. ASH Clinical News , 2019. [cited 2020 Jan 25] Available from: https://www.ashclinicalnews.org/spotlight/feature-articles/pediatric-hematology-oncology-small-specialty-experiencing-big-changes/

4. National Resident Matching Program. Results and Data: Specialties Matching Service [Internet]. 2019Available from: https://mk0nrmp3oyqui6wqfm.kinstacdn.com/wp-content/uploads/2019/02/Results-and-Data-SMS-2019.pdf

5. The Match, National Resident Matching Program. 2019 PSM Match Results Statistics Report [Internet]. 2019Available from: https://mk0nrmp3oyqui6wqfm.kinstacdn.com/wp-content/uploads/2019/12/417_MRS.pdf

6. Press Release: NRMP Releases Results of the Pediatric Specialties Match for Appointment Year 2020 - The Match, National Resident Matching Program [Internet]. The Match, National Resident Matching Program , 2019. [cited 2020 Feb 6] Available from: http://www.nrmp.org/press-release-nrmp-psm-2019/

If you are a member of the SOPT did you know?.......Calling all medical student, resident or fellowship trainee writers! The Section on Pediatric Trainees (SOPT) is currently seeking new submissions to the SOPT Monthly Feature in Pediatrics. The column features articles by pediatric trainees of all stages and is published on a quarterly basis. We accept submissions on a rolling basis and are looking for well crafted, relevant and thought-provoking articles on any topic. Please email SOPTpediatrics@aap.org with any questions.

AAP Section on Hematology/Oncology Newsletter - Spring 2020 Page 5

Clinical Feature: Hemostatic Mutations in Renal Vein Thrombosis*

Kevin Barton, MD, FAAP, Assistant Professor, Division of Pediatric Nephrology, Hypertension and Pheresis, Washington University School of Medicine in St. Louis

Renal vein thrombosis (RVT) is the most common non-catheter associated thromboembolic event in children. It predominately occurs in neonates, but the actual incidence is unknown. Myriad risk factors for RVT include many common neonatal conditions like sepsis, dehydration, respiratory distress syndrome, and prematurity. Maternal

risk factors also play an important, albeit unclear, role in pathophysiology. Maternal diabetes, oligohydramnios and preeclampsia increase the neonatal risk for RVT. In-utero twin deaths also increase the risk for unclear reasons. Recent research has focused on specific pro-coagulant mutations and the role these mutations play not only in the sentinel thrombotic event, but also in the risk for recurrence. The implications of these mutations and the need for anticoagulation remains a current topic of discussion and research, but prospective studies are still needed. This article will review what is known about normal neonatal hemostasis, the various mutations associated with RVT, and the associated risk of recurrent thrombosis.

Neonatal hemostasis is complex and different from childhood and adult hemostasis. The balance of pro and anti-coagulant protein levels differ likely due to the complex physiologic transitions in the neonatal period. By the tenth week of gestation, most hemostatic factors have been synthesized by the fetal liver. At birth, the components of these factors are identical to those of older children and adults. However, the plasma concentration and the activity of these components are drastically different, most likely due to different rates of synthesis, degradation and secretion. The maturation of these factors occurs over the first year of life, reaching adult levels by approximately one year of life. Coagulation factors in premature infants are similar to those of term infants, but notably the rate of maturation appears to be accelerated in premature infants. This is shown by equal levels of hemostatic factors at 6 months uncorrected age in preterm and term infants.

Neonatal coagulation factors differ both in pro and anticoagulant plasma levels and activity from older children and adults. The concentrations of vitamin K-dependent coagulation factors (II, VII, IX, X) are 25-70% of adult values.5 The concentrations of other pro-coagulant factors such as V, VIII, XIII, von Willebrand’s factor and fibrinogen at birth are near or higher than adults at 70-140% of adult values.5 Coagulation inhibitors such as protein C and S are approximately 50% of adult levels, but levels of other pro-coagulant factors are such as alpha-2-macroglobulin are double that of adults.5 Lastly, the levels of fibrinolytic factors show a similarly varied balance than in adults. Plasminogen and alpha-1-antiplasmin are lower in newborns than adults, but level of tissue plasminogen activator and plasminogen activator inhibitor-1 are higher.

Because of their immature coagulation system, premature neonates are potentially at increased risk of either bleeding or thrombotic events in response to perinatal stressors. Despite this, RVT remains more common among term infants than preterm infants. Several reviews have shown that 71% of infants with RVT were born after 36 weeks EGA, whereas 29% were <26 weeks EGA.2 The most common risk factor for RVT in the largest retrospective review to date was perinatal asphyxia (29%) which is more common in term infants, and may explain the higher incidence in term infants.2

Testing for pro-thrombotic risk factors has become more standardized, especially for neonates with spontaneous RVT vs those with multiple risk factors. However, the reasons for screening and the correlation of risk factors remains overall unknown. The mutations with the clearest pathogenic links to RVT include: Factor V Leiden, Protein C, S, deficiency, anti-thrombin III deficiency, and prothrombin deficiency. More recent studies have raised questions about elevated levels of lipoprotein a (lpa) as well as Factors VIII, IX and XI. Dysfibrinogenemias have also been posited to play a pathogenic role that is yet unconfirmed. Kosch et al performed an analysis comparing rates of pro-thrombotic risk factors between white neonates with RVT and healthy controls. On multivariate analysis, they found a significant higher odds ratio only for Factor V (OR, 9.4:95% CI, 3.3-26.6) and lp(a) (OR, 7.6; 95% CI, 2.4-23.8).1 On univariate analysis they found statistically significant higher odds ratios for FV, elevate lp(a), protein C deficiency, and increased anti-cardiolipin antibodies. Overall, they compared 59 infants with RVT with 118 healthy controls and found that 85.2% of infants with idiopathic RVT showed at least one pro-thrombotic mutation.1 54.2% of their cohort had multiple risk factors for RVT, but 67.8% of all patients had at least one pro-thrombotic mutation.1 This is similar to the review by Lau et al which cited an incidence of 53%, although this was in era where knowledge and testing of these mutations was lower.2 Furthermore, their cohort characteristics were also similar to the larger meta-analysis by Lau. Continued on Page 6

Page 6 AAP Section on Hematology/Oncology Newsletter - Spring 2020

The risk of recurrence for patients with a history of neonatal RVT and a pro-thrombotic mutation remains a controversial topic and there is scant literature with variable results. The largest cohort included 301 children and found 58% had a single pro-thrombotic mutation while 21% had combined inherited or acquired pro-thrombotic risk factors.4 Recurrent thrombosis occurred in 21% of patients with one or more risk factors.4 Also, the group found that patients with combined defects had shorter duration of event-free survival after discontinuation of anticoagulation. Marks et al found no recurrence in neonates after a similar median follow-up of 3.7 years compared to Kosch et al who found a 7% incidence of recurrent venous thrombosis in neonates with pro-thrombotic mutations.4

Renal vein thrombosis remains the most common thrombotic event in neonates conferring significant morbidity. The role of pro-thrombotic mutations remains unclear, but there is evidence to suggest a strong correlation. Further multidisciplinary studies are needed on more recent patient cohorts to clarify this relationship to further define the risk of recurrent thrombosis for these patients.

References:

1. Kosch, A., Kuwertz-Bröking, E., Heller, C., Kurnik, K., Schobess, R., & Nowak-Göttl, U. (2004). Renal venous thrombosis in neonates: prothrombotic risk factors and long-term follow-up. Blood, 104(5), 1356-1360. doi: 10.1182/blood-2004-01-0229.

2. Lau, K. K., Stoffman, J. M., Williams, S., McCusker, P., Brandao, L., Patel, S., & Chan, A. K. C. (2007). Neonatal Renal Vein Thrombosis: Review of the English-Language Literature Between 1992 and 2006. Pediatrics, 120(5), e1278-e1284. doi: 10.1542/peds.2007-0510.

3. Marks, S. D., Massicotte, M. P., Steele, B. T., Matsell, D. G., Filler, G., Shah, P. S., . . . Shah, V. S. (2005). Neonatal renal venous thrombosis: clinical outcomes and prevalence of prothrombotic disorders. J Pediatr, 146(6), 811-816. doi: 10.1016/j.jpeds.2005.02.022.

4. Nowak-Göttl, U., Junker, R., Kreuz, W., von Eckardstein, A., Kosch, A., Nohe, N., . . . Ehrenforth, S. (2001). Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors. Blood, 97(4), 858-862.

5. Resontoc, L. P. R., & Yap, H.-K. (2016). Renal vascular thrombosis in the newborn. Pediatric Nephrology, 31(6), 907-915. doi: 10.1007/s00467-015-3160-0.

* This article is re-printed with permission from the Fall 2019 issue of the AAP Section on Nephrology Newsletter.

Hot topics in Hematology/OncologyReviewed by: Eleny Romanos-Sirakis, MD, FAAP, Assistant Professor of Pediatrics, Staten Island University Hospital

Northwell Health, Zucker School of Medicine at Hofstra Northwell

1. Vichinsky E, Hoppe CC, Ataga KI, et al. A Phase 3 randomized trial of Voxelotor in sickle cell disease. NEJM. 2019;381:509-519.

On November 25, 2019, the Food and Drug Administration granted accelerated approval to voxelotor (Oxbryta, Global Blood Therapeutics) for adults and pediatric patients 12 years of age and older with sickle cell disease.

In the HOPE (Hemoglobin Oxygen Affinity Modulation to Inhibit HbS Polymerization) trial, the authors investigated the safety and efficacy of 2 dose levels of voxelotor (an HbS polymerization inhibitor that binds to hemoglobin and stabilizes the oxygenated hemoglobin state) with placebo in patients with sickle cell disease. This international, double-blind, placebo-controlled randomized trial, included 274 patients from 60 institutions with various genotypic variants of sickle cell disease, aged 12-65 years, who had 1-10 vaso-occlusive crises in the year prior. Two -thirds of the patients were taking baseline hydroxyurea. In an intention-to-treat analysis, which was performed when the last trial participant reached week 24, the percentage of patients who had a hemoglobin response was greater in the group treated with 1500 mg vexelotor orally daily (higher dose level), with an adjusted mean increase in hemoglobin of 1.1 g/dL over baseline in this treatment group. In addition, hemolysis lab markers were improved as compared to the placebo group. The most common adverse effects noted were headache and diarrhea, with most adverse events judged as unrelated to the trial drug. The incidence

Clinical Feature: Hemostatic Mutations . . . Continued from Page 5

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AAP Section on Hematology/Oncology Newsletter - Spring 2020 Page 7

of vaso-occlusive crisis did not differ significantly among the trial groups, and longer-term follow-up was planned for patients to assess the effect of voxelotor on vaso-occlusive crisis. The findings of this study suggest disease-modifying potential of voxelotor.

2. Young G, Ri Liesner, Tiffany Chang, et al. A multicenter, open-label phase 3 study of emicizumab prophylaxis in children with hemophilia A with inhibitors. Blood. 2019; 134:2127-2138.

The development of neutralizing anti-FVIII antibodies (inhibitors) leads to significant morbidity and mortality in patients with hemophilia A. Emicizumab, a bispecific humanized monoclonal antibody, bridges activated factor IX (FIX) and FX to restore the function of missing activated FVIII in hemophilia A. In this phase 3 trial (HAVEN 2), the investigators evaluated bleeding events in children with hemophilia A with FVIII inhibitors who previously were treated with prophylactic bypassing agents, after initiating subcutaneous emicizumab prophylaxis. 85 patients under age 12 years were enrolled and split into 3 dosing groups: 1.5 mg/kg weekly (group A), 3 mg/kg every 2 weeks (group B), or 6 mg/kg every 4 weeks (group C). Pharmacokinetics, safety, and efficacy (including an intraindividual comparison of participants from a noninterventional study) were evaluated. The annualized rate of treated bleeding events in children <12 years old was 0.3 in group A, 0.2 in group B, and 2.2 in group C. 77% of group A had no treated bleeding events. Intraindividual comparison of 15 participants who previously took prophylactic bypassing agents showed that emicizumab decreased the annualized bleeding rate by 99%. Participants also showed improvements across multiple domains of the Haemo-QoL-SF and Adapted Inhib-QoL questionnaires. The most frequent adverse events were injection site reactions and nasopharyngitis. The authors conclude that emiziumab prophylaxis was well-tolerated and efficacious, and may offer a new standard of care that reduces treatment burden and improves quality of life in patents with hemophilia A with inhibitors.

3. Curley A, Stanworth SJ, Willoughby K, et al. Randomized trial of platelet-transfusion thresholds in neonates. NEJM. 2019;380:242-251.

There is limited data providing guidance on prophylactic platelet transfusion thresholds for premature infants. In this multicenter study, 660 preterm infants (<34 weeks gestational age) with severe thrombocytopenia were randomized to receive platelet transfusions at a threshold of 50,000/ cubic mm (high threshold) vs 25,000/ cubic mm (low threshold). The included participants had a platelet count of <50,000/cubic mm, without ITP, intraventricular hemorrhage or major bleed within the last 72 hours. Primary study outcome was a composite of death or major bleeding through day 28; the primary outcome occurred in 26% of the high-threshold group and 19% of the low-threshold group. There were no significant differences between groups when evaluating rates of minor or worse bleeding. 90% of infants in the high threshold group and 53% of infants in the low-threshold group received at least 1 platelet transfusion. The authors concluded that more deaths or major bleeding occurred when a higher prophylaxis platelet transfusion threshold of 50,000/cubic mm was used as compared to a more restrictive threshold of 25,000/cubic mm, and that reducing the transfusion threshold from 50,000 to 25,000/ cubic mm may prevent major bleeding or death in 7 out of 100 preterm neonates with severe thrombocytopenia.

4. Mack JM, Verkamp B, Richter GT, et al. Effect of sirolimus on coagulopathy of slow-flow vascular malformations. Pediatr Blood Cancer. 2019;66:e27896.

Localized intravascular coagulopathy (LIC), leading to thrombosis and/or bleeding, are potential complications of slow-flow vascular malformations. In this retrospective chart review, 15 patients with vascular anomalies (slow-flow vascular malformations and pure venous malformations) who were prescribed sirolimus (rapamycin) were evaluated for improvement in laboratory test values and symptoms associated with LIC. D-Dimer levels, were initially abnormal in all patients, which is a reflection of increased fibrinolysis. After treatment with sirolimus, D-Dimer levels were significantly decreased and clinical symptoms, defined by pain and swelling, improved in 13/15 (87%) patients 3 months after starting sirolimus. The side effects in the study were reported as tolerable, while keeping trough levels of 5-15 ng/mL. However, long-term effects of sirolimus use in this patient population are unknown. The study is limited by several factors, including retrospective data collection and small patient sample, however, the authors conclude that the results of this study suggest that sirolimus therapy can improve the coagulopathy seen in slow-flow vascular malformations; this can, in turn, improve quality of life, and may decrease the need for additional anticoagulation in the perioperative period for those patients undergoing interventional or surgical procedures.

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5. Connolly ME, Bills SE, and Hardy SJ. Neurocognitive and psychological effects of persistent pain in pediatric sickle cell disease. Pediatr Blood Cancer. 2019;66:e27823.

Pain is a well-known complication of sickle cell disease (SCD), with acute pain crises contributing to increased disease morbidity and worse quality of life. Chronic pain, in general, is known to cause functional impairments, but there is limited data on the functional impairments of pediatric SCD patients with persistent pain. In this study, the authors sought to characterize persistent pain in a sample of patients with SCD and determine how these patients differ in physical, psychosocial, academic, and neurocognitive functioning from patients with sickle cell disease without persistent pain. The final analysis included 89 patients with SCD, aged 7-16 years. Information regarding the various categories of functioning was obtained using the PedsQL-SCD Module, Behavior Rating Inventory of Executive Function, Connors-third edition, Weschler Intelligence Scale for Children-fifth edition, Achievement tests (WJ-III, WIAT-III), and also included parental report of academic performance. Persistent pain was identified if the patient reported an response of “sometimes,” “always,” or “almost always” to the statement “I have pain every day” over the last week from the PedsQL-SCD Module, and was noted in 20% of patients in this study. In this study, patients with persistent pain were found to have worse HRQL and higher rates of defiance, aggression and behaviors associated with oppositional defiant disorder, in addition to increased difficulties with planning and organization, as described by caregivers, compared to counterparts without persistent pain. Patients with persistent pain also had lower scores in processing speed, working memory, and reading fluency, but intellectual functioning and caregiver estimation of academic performance did not differ between the two groups. The authors describe a sizable population of patients with SCD with persistent pain, distinct from episodic pain,0 and conclude that patients with SCD with persistent pain may be at higher risk for social-emotional challenges and neurocognitive deficits.

6. Li B, Niu Y, Ji W, et al. Strategies for the CRISPR-Based Therapeutics. Trends in Pharmacological Sciences. 2020; 41:55-65.

This review article provides an overview of the CRISPR (clustered regularly interspaced short palindromic repeats)- based genome editing technology, which is being investigated in various disease processes and targeting various genes. The review article also summarizes the clinical trials (both in the USA and abroad) using CRISPR-based therapy. This therapy has been utilized in patients with hemoglobinopathies, including sickle cell disease and beta thalassemia.

In December 2017, data from the pre-clinical trial regarding CTX100 were presented at the American Society of Hematology Annual meeting. (Lin M, et al. CRISPR/Cas9 Genome Editing to Treat Sickle Cell Disease and B-Thalassemia: Re-Creating Genetic Variants to Upregulate Fetal Hemoglobin Appear Well-Tolerated, Effective and Durable. Blood. 2017.) CRISPR/Cas9-based therapy has the potential to upregulate HbF and treat diseases of b-globin. In April 2019, the U.S. Food and Drug Administration (FDA) granted Fast Track Designation for CTX001 for the treatment of transfusion-dependent beta thalassemia (TDT).

In November 2019, CRISPR Therapeutics and Vertex announced early results from the first beta thalassemia patient treated with their CTX100 gene editing therapy in the CLIMB-Thal-111 Study for adult patients aged 18-35 years. CTX100 involves gene editing of a patient’s own hematopoietic stem cells (HSCs) using CRISPR/Cas9 gene editing technology in order to reactivate fetal hemoglobin production. This initial patient had transfusion-dependent beta thalassemia with a β0/IVS-I-110 genotype. She required 16.5 transfusions per year prior to enrolling in the study. Nine months after treatment with CTX001, this patient was transfusion-independent with a total hemoglobin level of 11.9 g/dL. A Phase 1/2 international clinical trial (CLIMB-SCD-121) was initiated in November 2018 to investigate the use of CTX001 in sickle cell disease in patients aged 18 to 35, with severe sickle cell disease. Preliminary results for the first patient given the treatment were reported in November 2019. Before treatment, the participant averaged 7 vaso-occlusive crises a year but 4 months after treatment was free of VOCs and had hemoglobin levels of 11.3 g/dl.

Reviewed by: Laura Rooms, MD, FAAP, Assistant Professor Pediatrics, The Jimmy Everest Center for Cancer and Blood Disorders in Children, University of Oklahoma Health Sciences Center.

1. J. Khan et al. Adolescent Patients with Hodgkin Lymphoma: A Children’s Oncology Group Study. J Clin Oncology, 2019; 37:3009-30017.

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Despite overall excellent prognosis for children and adolescents diagnosed with Hodgkin Lymphoma (HL), population studies have consistently shown survival disadvantages in non-white patients. The basis for these disparities is unknown; Khan et al looked at patients treated through the Children’s Oncology Group with newly diagnosed HL. Adjusting overall survival (OS) for clinical and treatment related variables, nonwhite patients had a 1.88 X higher hazard of death than white patients. Five-year post relapse survival rates were 90% for non-Hispanic whites, 66% for non-Hispanic blacks and 80% for Hispanics. This suggests a need for further investigation into treatment and survival disparities among racial groups.

2. L. Kelley et al. Pathological Fracture and Prognosis of High-Grade Osteosarcoma of the Extremities: An analysis of 2847 Consecutive Cooperative Osteosarcoma Study Group (COSS) Patients. J Clin Oncology, 2019; 38.

Metastatic osteosarcoma, the most common malignant bone tumor in children and young adults, continues to have a poor prognosis despite a standard treatment of neoadjuvant chemotherapy followed by surgery and adjuvant chemotherapy. Although pathological fractures (PFs) occur in 5-15% of patients with osteosarcoma, their prognostic significance is unclear. The COSS studied 2847 patients diagnosed with osteosarcoma from 1980-2010, of whom 321 (11.3%) had a pathological fracture at the time of diagnosis. Patients in their first decade of life had a 21.9% incidence of PF. They determined that PF had a significant negative impact on survival in the adult population, but not the pediatric population (5-year local recurrence incidence between pediatric patients with and without PF were 7.6% and 6.6%, respectively, p=.689).

3. J.E. Rubnitz, et al. Clofarabine Can Replace Anthracyclines and Etoposide in Remission Induction Therapy for Childhood Acute Myeloid Leukemia: The AML08 Multicenter, Randomized Phase III Trial. J Clin Oncology, 2019; 37(23): 2072- 2081.

Although overall survival rates for childhood acute myeloid leukemia (AML) now exceed 70%, additional intensification of induction regimens with the use of anthracycline and etoposide has not proven superior and carries a risk of late cardiotoxicity and secondary malignancy. Rubnitz et al evaluated the use of clofarabine for remission induction in a randomized multicenter trial that enrolled 285 newly diagnosed AML patients younger than age 22 who did not have Down Syndrome or APML. Day 22 minimal residual disease testing was positive in 47% of evaluable patients who received clofarabine + cytarabine and 35% of patients receiving standard induction with cytarabine, daunorubicin and etoposide. Despite this, however, 3-year event free survival and overall survival did not differ significantly between the two groups, suggesting that despite higher levels of day 22 MRD, clofarabine + cytarabine is an acceptable induction regiment with potential for lower long-term toxicity.

4. S. Jessop, et al. FDG-PET-CT in pediatric Langerhans cell histiocytosis. Pediatr Blood Cancer. 2020; 67:e28034.

Langerhans cell histiocytosis (LCH) has an annual incidence of approximately 4-4.5 per million and can present either with single system or multi system involvement, with skin and bone being the most commonly affected sites. Since therapy is highly dependent on extent of disease involvement, having accurate imaging modalities is essential. For this reason, Jessop et al reviewed the performance of FDG PET-CT in staging and follow up of 33 patients with biopsy proven LCH from 2006-2017. Over 100 scans were analyzed, with average patient follow up of 3.4 years. Overall sensitivity and specificity of FDG PET-CT were 100% and 83%, respectively. Therefore, this modality may prove useful both in evaluating disease activity at diagnosis as well as at follow up when physical exam and/or other imaging modalities are equivocal.

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Clinical Feature: Clostridioides (Clostridium) Difficile Infection in Children: Highlights of the Updated Guidelines

from the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA)*

Thomas J. Sandora, MD, MPH,Hospital Epidemiologist, Division of Infectious Diseases,

Boston Children’s Hospital, Boston, MA

Brief case

A healthy 7-year-old boy presents with a 2-day history of watery diarrhea. He has not had fever or vomiting. There are no sick contacts at home or school. He is currently receiving amoxicillin (day 8 of 10) for treatment of streptococcal pharyngitis. Stool is sent for C. difficile PCR and returns positive. Which treatment option would you recommend?

A. Discontinue amoxicillin and observe for resolution of diarrheaB. Discontinue amoxicillin and start oral metronidazoleC. Continue amoxicillin and add oral metronidazoleD. Continue amoxicillin and add oral vancomycin

The correct answer to this question is that there isn’t really consensus about the best option for management in this particular situation (but options C and D are both reasonable to consider; for this patient, A and B are less preferred because completing the 10 days of amoxicillin for streptococcal pharyngitis is recommended for prevention of rheumatic fever). The 2017 update of the Infectious Diseases Society of America (IDSA)-Society for Healthcare Epidemiology of America (SHEA) clinical practice guidelines for C. difficile infection (CDI) included, for the first time, dedicated recommendations for diagnosis and management of CDI in pediatric patients.1 This article will review key highlights from these guidelines, with a focus on diagnosis and treatment of CDI in children.

Epidemiology

Clostridioides difficile (previously called Clostridium difficile) is an anaerobic spore-forming Gram-positive bacillus. Strains that produce toxin are capable of causing clinical disease (CDI), which typically manifests as watery diarrhea and may be accompanied by low-grade fever or mild abdominal pain. Severe or fulminant disease is less common but may include hypotension, ileus, or toxic megacolon. The most important modifiable risk factor for CDI is exposure to antibiotics, with specific antibiotic classes (including third- and fourth generation cephalosporins, fluoroquinolones, carbapenems and clindamycin) carrying a high risk because of the associated disruption of the intestinal microbiota. Within healthcare settings, the most likely routes of transmission of C. difficile are via the hands of healthcare workers and environmental contamination.

The most important feature of the epidemiology of C. difficile in children is the high rate of asymptomatic colonization. The highest rates are in infants, in whom colonization rates can be >40%. Colonization decreases with increasing age, such that by 2-3 years of age, approximately 1-3% of children remain colonized. When a child less than 2 years old develops diarrhea, it is difficult for a provider to determine whether a positive test for C. difficile represents a true infection vs. detection of colonization with an alternate reason (either infectious or noninfectious) for diarrhea. For this reason, the new guidelines discourage public reporting of CDI cases (for surveillance purposes) in children <2 years of age, to minimize misclassification.

Diagnosis

For adults, the guidelines recommend the preferred target population for C. difficile testing be patients with new onset of 3 or more unformed stools in a 24-hour period, without an alternate explanation for diarrhea. In children, there is no universally accepted definition of clinically significant diarrhea, but sustained diarrhea without a likely alternate explanation should be present before C. difficile testing is undertaken. In stable children who are receiving laxatives

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or stool softeners, discontinuing these agents should be strongly considered to assess for resolution of unformed stool before testing for C. difficile. The guidelines recommend not routinely testing for C. difficile in infants who develop diarrhea, because of the increased likelihood of detecting colonization as described above.

This recommendation matches the language from the C. difficile chapter of Red Book® 2018, which discourages testing of infants.2 For children between ages 1 and 2 years, the IDSA-SHEA guidelines recommend excluding other noninfectious and infectious causes of diarrhea before consideration of C. difficile testing. In children≥2 years of age, testing is reasonable for patients who have risk factors (i.e., antibiotic exposure, hospitalization) and prolonged or worsening diarrhea.

Providers often do not have influence over which C. difficile testing method is available at the location in which they practice. However, the new guidelines suggest using an approach that includes a stool toxin test as part of a multi-step algorithm rather than a nucleic acid amplification test (NAAT) alone, because a NAAT detecting the genes for toxins A and/or B has low-to-moderate positive predictive value (i.e., a positive result may reflect asymptomatic colonization with a toxigenic organism rather than actual toxin production and true CDI). Multi-step algorithms are recommended because the sensitivity of a toxin enzyme immunoassay alone is still not high enough to reliably use it as a stand-alone approach for diagnosis.

Repeat testing should not be performed within 7 days during the same episode of diarrhea. There is also no value to testing for cure, as >60% of patients may still test positive for several months despite successful treatment.

Treatment

For adults with CDI, the new guidelines recommend using oral vancomycin or fidaxomicin (and not metronidazole) as first-line agents for treatment both for mild-moderate and severe CDI. This recommendation is based on data from randomized controlled trials of adult patients that showed oral vancomycin to be superior to oral metronidazole in achieving clinical cure. Evidence of the comparative effectiveness of these two agents for treating pediatric CDI is lacking, and accumulated experience of using metronidazole to treat mild-moderate CDI in children suggests good outcomes. For this reason, the guidelines endorse either metronidazole or oral vancomycin for 10 days as appropriate choices to treat a first episode of mild-moderate disease in a pediatric patient. The Red Book® 2018 lists metronidazole as the preferred treatment for a first episode of mild-moderate CDI but suggests considering a switch to vancomycin if there is failure to respond in 5-7 days.2 Oral vancomycin should be used for severe or fulminant CDI, as previously recommended. Once a patient has had 2 or more episodes of recurrent CDI, metronidazole should no longer be used for treatment because of its potential for neurotoxicity when given in prolonged or repeated courses; instead, tapered or pulse regimens of vancomycin are often used. For the first time, the guidelines provide a dedicated table outlining the recommended treatment options for pediatric CDI, including antibiotic dosing. Of note, fidaxomicin has not yet been approved by the Food and Drug Administration for treatment of patients less than 18 years of age, but data from clinical trials in children are now available to help guide dosing with an eye towards future FDA approval.

Although robust pediatric data are lacking, fecal microbiota transplantation (FMT, installation of donor stool into the gastrointestinal tract to restore the diversity of intestinal microbiota) has been shown in limited case reports and case series to be effective in children with CDI. Because of concerns about potential unintended long-term infectious and non-infectious consequences of this approach, the guidelines recommend not considering FMT for children with CDI unless there have been multiple recurrences despite treatment with recommended antibiotic regimens.

References:

1. McDonald LC, Gerding DN, Johnson S, et al. Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis. 2018.

2. American Academy of Pediatrics. Clostridium difficile. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018:288-292.

* This article is re-printed with permission from the Spring 2019 issue of the AAP Section on Infectious Diseases Newsletter.

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Tech TipSimply Sayin’™ - Medical Jargon for Families

This free app was created by Phoenix Children’s Child Life Specialists to make it easier for healthcare providers to use “soft language” to talk to kids and families about medical issues. Never heard of “soft language”? One way to describe it is “developmentally appropriate explanations of medical terminology”. This excerpt from the glossary provides a good example: “Amputation = An operation (surgery) to remove a body part that is sick or injured and cannot be made better.” All the information is available in Spanish.

The app also provides photos of CT and MRI scanners, drawings of central venous lines, and diagrams of the body that you can draw on. It also emphasizes the “teach-back” method for communicating with patients and families. This app can be a great tool to help make pediatric and pediatric subspecialist daily encounters more kid-friendly and also accurate. System requirements: iPhone, iPad. Requires iOS 8.0 or later.

*Inclusion of this information within this communication does not represent endorsement of the product by the AAP or the Section on Hematology/Oncology but is being shared as an information only.

“I am teaching but are they learning?”: Maximizing learning for the millennial generation

Eleny Romanos-Sirakis, MDAssistant Professor of Pediatrics, Zucker School of Medicine at Hofstra Northwell,

Pediatric Hematology/Oncology, Staten Island University Hospital Northwell Health As clinicians in pediatric hematology/oncology, educating trainees is a substantial and meaningful part of our careers, with both great rewards and challenges. We spend a significant amount of time preparing and presenting lectures for trainee education, but are often left wondering: how much do they really learn? In order to optimize the learning process, we must first acknowledge the ways adults learn best as well as the distinguishing factors of the current millennial trainees.

Resident education is often based around lectures in a variety of settings, most commonly with grand rounds, noon conferences and pre- or post-outpatient clinic lectures. The “60-slide power-point lecture” is a common basic staple for education, though many educators feel a pressure to go beyond this type of teaching and learning experience. Considering that the average retention rate of new learning for a lecture is only 5%1, we must strive to move away from the traditional passive lecture and apply adult learning principles within our teaching to promote and maximize student, resident and fellow learning.

The schedule of the residents and fellows during the day is often unpredictable and busy. Trainees have a multitude of tasks to complete for their patients as well as their own education. The busy workload of a trainee can be a barrier to learning, as the educational sessions compete with the desire and need to complete tasks.2 Several documented features contribute to residents’ motivation to attend lectures.2 The lectures should be clinically relevant and practical, as well as appropriate to the level of the learner. In addition, focused and limited learning points delivered over a shorter time period are preferred. These preferences align with several educational assumptions of adult learning described by Knowles decades ago.3,5,6

In addition to being limited on time, cognitive psychology teaches us that the typical adult learner attention span wanes after approximately 15-20 minutes.3,4 Thus, didactic sessions are best when interspersed with active teaching and learning methods that promote application of new knowledge. We can optimize the 1-hour educational sessions by breaking up the session into segments of teaching accompanied by segments of engaging activities.4

Incorporating adult learning theory includes the consideration of the learners’ self-concept, past experiences, orientation to learning, and motivation to learn.5,6 Adult learners have various competing demands on their time and so prioritizing a learning experience will be affected by how much the material aligns with their perceived goals or objectives. Each

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adult learner also comes to every educational session with their unique pre-existing knowledge, deficits, and experiences. Learners must feel that material is directly applicable to their immediate situation, and internal motivations drive learner behavior. In addition, the learners bring expectations of the teacher to the learning environment and benefit from a collaborative learning environment.

It is important to tune into the learners’ motivations to learn by identifying their needs and providing education on topics immediately relevant to them. It is also beneficial to specify how the information might be useful for them. Adapting the lecture to address a knowledge deficit in light of the trainees’ prior experiences and introducing new concepts by relating them to what is already known is optimal and requires sharing of baseline experiences. Adult learners want some control over what they are learning and should be encouraged to have some degree of independence in the learning process and contribute to the learning of their colleagues. Lastly, adult learners are busy, practical and learn by doing. They learn best when there is an immediate application for the learning, and they participate actively in the learning process during the session.

In addition to facing the nuances of teaching adults, we must be aware of the distinguishing features of the trainees of the millennial generation. Millennials have unique perspectives on the world, their interactions with others, and their learning.7,8 I suspect many reading this article may have caught themselves, at one time or another, questioning the work ethic or style of the millennial generation. We can learn a lot about how millennials learn and connect better with them by understanding the experiences of their generation. Ultimately, our goal is to help our trainees maximize their learning from the time we devote to teaching.

People from different generations often have different baseline experiences and expectations. Understanding these differences and adapting educational models to target the learners’ needs may optimize teaching and learning for our future colleagues. For example, Traditionalists (born between 1925 and 1945) are described as having a strong work ethic and prefer lectures. The Baby Boomers (born between 1945 and 1964) often feel that careers define them, and they are extremely dedicated and competitive. Members of Generation X (generally defined as those born between 1965 and 1982), the generation prior to the millennial generation, tend to use technology more than the prior 2 generations, are described as being more cynical and impatient, and dislike rigid work requirements, as they look for more of a balance between work and life, making family more of a priority.7

Millenials grew up in a “child-centric” generation with extensive parental involvement and a booming economy. Overall, they are described as having shorter attention spans that may require instructors to engage them in each educational interaction. Millennial trainees are comfortable asking for or expecting support to be there rather than problem-solving first. Providing structure to activities, setting specific targets and goals, and providing specific and timely feedback of observed performance have been suggested to optimize millennial learning. Ultimately, millennial learners benefit from consistency, reassurance, and reminders that they are learning within a fair and reasonable framework.7,8

Millennial learners also tend to be more visual communicators (think: graphics and “YouTube”). In practice, they are explorative, hands-on, and team oriented. Millennials thrive on social networking; it may be beneficial for teachers and mentors to try to make a connection by sharing how you got to where you are and why you enjoy doing your work, as well as how you balance work and life. Interactive and engaging materials work best; utilizing technology to enhance learning and make presentations that are aesthetically appealing appear to facilitate learning for this group.7,8

Identifying key features of our learners will help to optimize the learning process for them. Incorporating the learners preferred methods into the learning process, utilizing active learning techniques, specifying the relevance of material, providing clear and consistent expectations as well as timely feedback are among the opportunities to optimize learning for the millennial adult learners.

References:

1. Masters K. Egdar Dale’s Pyramid of Learning in medical education: a literature review. Med Teach. 2013;35:e1584-93.

2. Sawatsky AP, Zickmund SL, Berlacher K, et al. Understanding resident learning preferences within an internal medicine noon conference lecture series: a qualitative study. J Grad Med Educ. 2014;6(1):32-38.

3. Cooper AZ, Richards JB. Lectures for adult learners: breaking old habits in graduate medical education. AAIM.

“I am teaching but are they learning?”: Maximizine learning . . . Continued from Page 12

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2016;130(3):376-381.

4. Lenz PH, McCallister JW, Luks AM, et al. Practical strategies for effective lectures. Ann Am Thorac Soc. 2015;12(4):561-6.

5. Knowles M. The adult learner: a neglected species. Houston TX: Gulf 1988.

6. Adult learning theories: implications for learning and teaching in medical education: AMEE Guide No. 83. Med Teach. 2013;35:e1561-72.

7. Aaron M & Levenberg P. The millennials in medicine: tips for teaching the next generation of physicians. J Acad Opth. 2014;7:e17-20.

8. Roberts DH, Newman LR, and Schwartzstein RM. Twelve tips for facilitating millenials’ learning. Med Teach. 2012;34:274-78.

Coding Update: Changes to Red Blood Cell Exchange –Automated and Manual

During the February 2020 CPT Editorial Panel meeting, there was a request to add cross references that direct users to the appropriate codes to report automated red cell exchange (36512) and manual red cell exchange (36450, 36455, 36456) following codes 36450 and 36512.

The Panel recommended that an article be published in the CPT Assistant to explain automated versus manual red cell exchange as well as the codes used to report these services.

The AMA recommended making this action effective for CPT 2021 code set rather than CPT 2022 to stop the inappropriate reporting of manual versus automated red blood cell exchange as early as possible.

For example, see underlined parentheticals below:

36450 Exchange transfusion, blood; newborn

(When a partial exchange transfusion is performed in a newborn, use 36456

(Do not report modifier 63 in conjunction with 36450)

(For manual red cell exchange, see 36450, 36455, 36456)

(For automated red cell exchange, use 36512)

36455 other than newborn

36456 Partial exchange transfusion, blood, plasma or crystalloid necessitating the skill of a physician or other qualified health care professional, newborn

(Do not report 36456 in conjunction with 36430, 36440, 36450)

(Do not report modifier 63 in conjunction with 36456)

36511 Therapeutic apheresis; for white blood cells

36512 for red blood cells

(For manual red cell exchange, see 36450, 36455, 36456)

(For automated red cell exchange, use 36512)

36513 for platelets

(Report 36513 only when platelets are removed by apheresis for treatment of the patient. Do not report 36513 for donor platelet collections)

36514 for plasma pheresis

(36515 has been deleted. For therapeutic apheresis with extracorporeal immunoadsorption and plasma reinfusion, use 36516)

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Coding Update: Changes to Red Blood Cell Exchange . . . Continued from Page 14

36516 with extracorporeal immunoadsorption, selective adsorption or selective filtration and plasma reinfusion

(For professional evaluation, use modifier 26)

If you or any of your coding team have thoughts for a new code or have any questions or concerns about the ICD-10-CM code set, please reach out to the AAP’s coding hotline aapcodinghotline@aap.org.

To Be or Not to Be a Research-Mentor in PediatricsMichael R. DeBaun, MD, MPH

Professor of Pediatrics and Medicine, Vanderbilt University School of Medicine

Few traditions in academic institutions are more time tested than the relationship between a mentor and mentee. The common definition of mentor in pediatrics has taken on a broad range, including career-mentor, peer-mentor, academic-mentor and research-mentor. The most- time intensive mentor-mentee relationship is the research-mentor.

Becoming a research-mentor is a challenging proposition for both the mentor and the mentee. Typically, the research-mentor interactions are forged early in the residency or fellowship based on familiarity, proximity, and clinical interests rather than tangible metrics that increase the prospect of success for the mentee and accelerate discovery.

Research-mentor selection should be primarily based on objective parameters that increase the likelihood of achieving the desired objectives for both the mentor and mentee during the research period. One of the biggest challenges is ensuring that there are agreed upon objectives prior to starting the research period. These expectations should be formally expressed, written and re-visited during the research period. External review committees, often referred to as scholarship oversight committees, often review these objects and assess the progress toward achieving their desired objectives. However, these committee rarely can address the quality of the mentor-mentee relationship.

Essential criteria for selecting a mentor should include factors such as the mentor’s publication record, funding, and prior mentee productivity. The research mentor that has not published a manuscript as a senior author in the last 3 years, is far less likely to be productive in supporting the research career of the mentee that has published 10 senior manuscripts in the last year. A quick review of the publication record with specific attention to senior authorship (last author, and often reserved for the leader of the laboratory) in Pubmed (https://www.ncbi.nlm.nih.gov/pubmed/) will inform the potential mentee of the publication productivity. The absence of any senior authorship manuscripts of the mentor raises the question of the ability of the potential mentor to support the mentees aspiration for a significant research experience.Similarly, the absence of current or recent peer reviewed mentor funding decreases the chances that the mentees applications will be reviewed favorably for future competitive peer reviewed funding. A quick review of NIH Reporter (https://projectreporter.nih.gov/reporter.cfm), a search engine identifying NIH sponsored research, will provide the complete NIH funding history of potential mentors that have been principal investigators of NIH funded awards. The mentee will have to distinguish between mentors that are site investigators for clinical trial networks from mentors that are principal investigators of NIH funded studies. Site investigators for NIH clinical studies are not listed in NIH Reporter. The absence of funding in the NIH Reporter, should not be interpreted as no past or active funding, but rather no record of NIH funding as a principal investigator. Many investigators receive investigator-initiated grants from sources other than NIH, such as private foundations, and their funding source will not be listed in the NIH Reporter.

Most competitive peer reviewed mentored awards, including NIH sponsored mentored awards, judge an application based on the applicant’s academic performance, the quality of the research proposal, the mentor’s track record of funding and prior mentorship experience. A mentee, that selects a mentor without recent publications and without current or recent reviewed funding, significantly lowers the chances that their application will receive peer reviewed funding.

Often a mentee will select to work with an early career investigator or even a senior investigator that has limited discretionary funding and limited experience in mentoring. In such situations, the best solution is tiered mentoring or co-mentoring, where at least one mentor has a significant track record for both securing peered reviewed funding, successful mentees, and a strong senior author publication record.

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Even if the mentor has a significant track record of recent publications and current funding, identifying the right fit between the mentor and mentee is critical for a successful relationship. Seeking to understand the culture of the research laboratory can be a challenging proposition for the mentee, but is crucial to maximize the best fit. Open discussion with the mentor, post-doctoral fellows or staff about expectations is important. Informal discussions with current and past members of the current laboratory is a great opportunity to understand the culture of the laboratory. The table below describes the tone of expectations that I set in my clinical research laboratory.

Establishing a separate research trajectory for mentees working with their mentor is a challenging, but critical component of the relationship. Ultimately when the tenure for the research mentor-mentee relationship comes to an end, there is an expected tension as to whether the mentee’s project is transferable to another institution or even within the same institution. Setting expectations early as to which project is transferable outside of the laboratory and which projects must stay within the laboratory can provide a successful strategy for transition. When successful transitions occur, the mentee becomes not just a former mentee, but a collaborator and potentially a multi-principal investigator on future grants.

As a pediatrician, and pediatric hematologist, I have had the pleasure of seeing our newborns become young adults, physicians, nurses, mothers, fathers. These experiences have provided internal validation for the joys of pediatrics. Equally as important, I have enjoyed the internal satisfaction of having my former mentees develop their own research trajectory, with independent funding and outstanding contributions to medicine. Watching former mentees establishing their own clinical research programs has been a source of pride and joy. As I eventually transition to not providing patient care, I look forward to contributing in some small way to the scientific and career support of my small cadre of mentees. Truly being a research mentor in pediatrics is the gift that keeps on giving.

To address many of the before mentioned barriers for establishing a successful research mentor-mentee relationship, I have established the following 10 cardinal rules in my laboratory:

1. I will not work harder on your project than you.

2. I will not be your rate-limiting step for your manuscript, grant, or project.

3. We must celebrate the process of submitting a grant with a lunch (my treat) and celebrate again with a lunch (my treat) if we get the grant.

4. Write grants when you do not currently need the funding for your academic salary support.

5. There should be no time period when we are not writing a grant, manuscript, or both.

6. Whatever, I do for you as a mentor, I expect you will do for others when you become a mentor.

7. Mentor someone else junior to you because mentoring is an acquired skill that take years to refine.

8. Routinely read books outside of medicine for self-improvement and self-discovery and to hone your leadership style, critical thinking, and abilities. (As a laboratory exercise, we regularly read books or articles about leadership.) We will discuss these books and your progress during weekly laboratory meetings.

9. Initially, select one area to focus your research on. When your research has matured, you can branch into another domain.

10. Have fun while experiencing the joy of discovery to advance the medical care for our families. If you’re not having fun or feeling the energy, do not pursue research as your primary career choice.

Join the AAP Mentorship ProgramMentorship is one of the most important tools for professional development and has been linked to greater productivity, career advancement, and professional satisfaction. The AAP recognizes that mentorship is critical in helping to nurture and grow our future leaders and that a mentorship program is a key opportunity to engage new and existing members. The AAP Mentorship Program seeks to establish mentoring relationships between trainees/early career physicians and practicing AAP member physicians. Click here for more information and to join the program.

To Be or Not to Be ... Continued from Page 15

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AAP Section on Hematology/Oncology Newsletter - Spring 2020 Page 17

Please note: Mentors are asked to commit at least one full year. However, the program offers opportunities for short-term “flash” mentoring. Mentors/mentees will be asked to set regular phone meetings to discuss mentee goals, objectives, and progress. Mentors/mentees should also answer all communications in a timely manner.

Sickle Cell Disease Coalition (SCDC) UpdateThe mission of the SCDC is to amplify the voice of the SCD stakeholder community as well as promote awareness and improve outcomes for individuals with SCD. The Coalition will focus on promoting research, clinical care, education, training, and advocacy. The SCDC serves as a platform to encourage stakeholders to work together to develop and implement important projects and activities that will ultimately help to improve outcomes for individuals with SCD.

View the April edition of the SCDC Update regarding resources and ways you can help raise awareness. Previous issues of the SCDC Update and a subscription form to the e-newsletter are available here on the SCDC Coalition website. We encourage you to share this information with your colleagues who have an interest in sickle cell disease.

SOHO Collaboration Site!As a member of the AAP Section on Hematology/Oncology (SOHO) you have access to the SOHO Collaboration Web site. This member’s only benefit of the SOHO grants each current Section member access to the following:

• Opportunities to get involved in the SOHO leadership committees and policy review groups.

• Information for trainees regarding a career in pediatric hematology/oncology.

• Section publications including the newsletter and AAP News articles.

• Quick access to new and/or existing AAP policies developed by SOHO and practice guidelines of interest to SOHO members.

And much more!

View Access Instructions below. For questions or suggestions regarding the SOHO collaboration site please contact SOHO Staff, Suzanne Kirkwood or the SOHO Chair, Dr Zora R. Rogers.

Step 1: Visit http://www.aap.org click on “My Collaboration Sites”“My Collaboration Sites” at the top of the webpage.

Step 2: Log in with your AAP login credentials.

Step 3: Access your Section collaboration site

Step 4: Begin navigating your site. Note- You can bookmark your site for future use

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Page 18 AAP Section on Hematology/Oncology Newsletter - Spring 2020

Welcome to Our New MembersIf you know of others who might be interested in joining the Academy and the Section please refer them to the AAP website membership page. Thank you to all who have continued to support the AAP and the Section by renewing their memberships. And welcome to new members of the Academy and the Section!The Section on Hematology/Oncology Executive Committee

For Upcoming Newsletters . . .We welcome your input and encourage you to submit ideas or information

by email to Carl Allen, MD FAAP at ceallen@txch.org or Suzanne Kirkwood at skirkwood@aap.org for future issues of the newsletter.

The Section on Hematology/Oncology Executive Committee

Chairperson:Zora R. Rogers, MD, FAAP

Executive Committee:Carl Allen, MD, PhD, FAAPJames Harper, MD, FAAP

Juhi Jain, MD, FAAPJeffrey Lipton, MD, PhD, FAAP

Cynthia Wetmore, MD, PhD, FAAPAmber Yates, MD, FAAP

Immediate Past-Chair:Jeffrey Hord, MD, FAAP

Liaisons:David Dickens, MD, FAAP

Alliance for Childhood Cancer

Cynthia Wetmore, MD, PhD, FAAP Council on Pediatric Subspecialties

Staff:Suzanne Kirkwood, MS

Manager, Section on Hematology/Oncology

Journal Production SpecialistMark A. Krajecki

Statements and opinions expressed in this publication are those of the authors

and not necessarily those of the American Academy of Pediatrics

or the AAP Section on Hematology/Oncology.