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Francis Collins

Francis S. Collins, M.D., Ph.D. from NIH: The future of genomic medicine and research funding opportunities

Kurt Newman and Francis Collins

Genomic medicine, diversity, equity and inclusion (DEI), a world post-COVID-19 and pediatric research funding were among the topics discussed during the “Special Fireside Chat” keynote lecture at the 2021 Children’s National Hospital Research, Education and Innovation Week.

Francis S. Collins, M.D., Ph.D., director at the National Institutes of Health (NIH), is well known for his landmark discoveries of disease genes and his leadership of the international Human Genome Project, which culminated in April 2003 with the completion of a finished sequence of the human DNA instruction book.

The President and CEO of Children’s National, Kurt Newman, M.D., joined Dr. Collins during the “Special Fireside Chat” keynote lecture. Dr. Newman posed several health care-related questions to Dr. Collins over the course of 30 minutes. Dr. Collins’s responses shed light on what it takes to advance various research fields focused on improving child health and develop frameworks that advocate for DEI in order to foster a more just society.

Q: You have been involved with genomic medicine since its inception. You discovered the gene causing cystic fibrosis and led the Human Genome project. What do you see as the future of genomic medicine, especially as it relates to improving child health?

A: Thank you for the question, Kurt. First, I wanted to say congratulations on your 150th anniversary. Children’s National Hospital has been such a critical component for pediatric research and care in the Washington, D.C., area, and at the national and international levels. We at the NIH consider it a great privilege to be your partner in many of the things that we can and are doing together.

Genomic medicine has certainly come a long way. The word genomics was invented in 1980, so we have not been at this for that long. Yet, the success of the Human Genome Project and the access to cost-effective tools for rapid DNA sequencing have made many things possible. It took a lot of effort, time and money to discover the gene that causes cystic fibrosis. Kurt, if you look at what we did, while it was rewarding, it was a challenging problem that occupied the hearts of the scientific community in 1980. Now, a graduate student at Children’s National that has access to DNA samples, a thermal cycler, a DNA sequencer and the internet could do in about a week what it took us a decade and with 50 people.

We have been able to rocket forward as far as identifying the genetic causes of 6,500 diseases, where we know precisely the molecular glitch responsible for those conditions. While most of those are rare diseases, it leads to the opportunity for immediate diagnosis, which used to be a long and troubled journey.

DNA sequencing has increasingly become an essential tool in newborns, especially when trying to sort out puzzling diagnosis for specific syndromes or phenotypes that are not immediately clear. Additionally, DNA sequencing significantly impacted clinical care in cancer because it made it possible to look at the mutations driving the malignancy and its genetic information that can lead to interventions. This approach is going forward in the next few years in ways that we can see now. Although I am a little reluctant to make predictions because I have to be careful about that, it may be possible to obtain complete genome sequences that can be yours for life and place them into the medical record to make predictions about future risks and choices about appropriate drugs. This path costs less than any imaging tests.

Q: The racial justice movement that was brought back to the forefront this past year has, once again, reaffirmed that this country has so much more work to do in order to end systemic racism. You have been at the forefront of promoting diversity, equity and inclusion in research and at the NIH. What do you and the NIH plan to do further DEI efforts in research and in general so that we can be a more just and equitable society?

A: I appreciate you raising this, Kurt. Diversity, equity and inclusion (DEI) is an issue where everyone should be spending a lot of time, energy and passion. You are right. 2020 will be remembered for COVID-19. I also think it will be remembered for the things that occurred around the killing of George Floyd, and the recognition of the very foundation that is still infected by this terribly difficult circumstance of structural racism. I convened a group of about 75 deep thinkers about these issues, many of them are people of color from across the NIH’s different areas of activities. I asked the group to come forward with a bold set of proposals. This effort is how the program UNITE came together to work hard on this, which is now making recommendations that I intend to follow. We are determined to close that gap and pursue additional programs that will allow us to be more successful in recruiting and retaining minority groups, for example. We need to do something with our health disparity and research portfolio as well to ensure that we are not just looking around the edges of the causes for racial inequities. We are digging deeper into what the structural racism underpinnings are and what we can do about it. I am particularly interested in supporting research projects that test intervention and not just catalog the factors involved. We have been, at times, accused and maybe rightly so of being more academic about this, and, less kindly, we have been accused of admiring the problem of health disparities as opposed to acting on it. We are ready to act.

Q: COVID has affected us all in so many ways. Could you tell us what this past year has been like for you? Also, how is the NIH preparing for a soon-to-be post-COVID pandemic?

A: This is the time to contemplate the lessons learned as everyone knows that the last worst pandemic happened over a century ago. One thing that maybe will vex us going forward, which we already started to invest in a big way, is this whole long COVID syndrome, also referred to post-acute sequelae, to understand precisely the consequences and mechanisms like Multisystem Inflammatory Syndrome in Children (MIS-C). Before moving to the next pandemic, we must think about how we will help understand those who suffer from long COVID syndrome. As far as the broader lessons learn, Kurt, we must expect that there will be other pandemics because humans are interacting more with animals, so zoonosis is likely to emerge. We need to have a clear sense of preparation for the next one. For instance, we are working on this right now, but we need to have a stronger effort to develop small molecules of anti-viral drugs aimed at the major viral classes, so we do not have to start from scratch. We also need clinical trial networks warm all the time, ready to go and to learn how valuable public partnerships can be to get things done in a hurry.

Editor’s Note: The responses in this Q+A have been modified to fit the word count.

Little boy going to school with protective mask

Firearm injuries involving young children in the United States during the COVID-19 pandemic

Little boy going to school with protective mask

After seeing the surge of firearm injuries in young children and inflicted by young children during the first six months of the COVID-19 pandemic, the study’s experts are saying there is an urgent and critical need for enactment of interventions aimed at preventing firearm injuries and deaths involving children.

A recent study pre-published in Pediatrics found that the COVID-19 pandemic is associated with a surge in fatal and nonfatal firearm injuries both in young children and inflicted by young children, correlating with a rise in firearm acquisitions.

The findings, led by Children’s National Hospital experts, show the risk was higher during the first six months of the COVID-19 pandemic as compared to the pre-COVID period.

“According to the Centers for Disease Control and Prevention, firearms are a leading cause of injury and death among youth,” said Monika K. Goyal, M.D., M.S.C.E., senior author of this study and associate  chief of Emergency Medicine and Trauma Services at Children’s National. “The pandemic has led to an increase in these preventable tragedies and it is incumbent upon us as a society to put appropriate measures in place to keep children safe.”

“Increased firearm purchases are one reason we have seen an increase in firearm injuries during the pandemic,” said Joanna S. Cohen, M.D., associate professor of Pediatrics and Emergency Medicine. “Increased purchases are likely related to the political unrest we recently witnessed and increased firearm injuries may be related to children being at home more. Whereas children were in school before, they might be home unsupervised while parents and caretakers are working.”

In addition, there has been an increase in domestic violence over the course of the pandemic which, according to Dr. Cohen, could be a reflection of the stress emerging from financial insecurity, joblessness, illness and other stressors deriving from the pandemic.

After seeing the surge of firearm injuries in young children and inflicted by young children during the first six months of the COVID-19 pandemic, the study’s experts are saying there is an urgent and critical need for enactment of interventions aimed at preventing firearm injuries and deaths involving children.

“There is an urgent need for strategies to prevent further injuries,” Dr. Goyal said. “This includes counseling families on firearm safety at home, having more sensible gun laws and educating the public accordingly.”

In the past, if you were a new gun owner, you would have access to training on how to handle a gun and find safe storage. With all the sheltering in place due to the pandemic, those educational opportunities have fallen by the wayside. “Now you have more people who have become new gun owners but haven’t had the opportunity to get education on safe gun ownership, coinciding with more children staying at home because of the pandemic,” Dr. Goyal said.

The increase in domestic violence could also be a contributing factor. Children are often witnesses to violence at home, Dr. Cohen explained. In many cases, she said, if children see a parent being threatened with a gun, they might model that behavior without fully understanding the implications of holding a gun and the injury it can cause.

using a laser to cut PPE face shields for staff during covid-19

Multidisciplinary team develops innovative PPE that fits clinical needs during COVID-19

using a laser to cut PPE face shields for staff during covid-19

Children’s National engineers and clinicians developed plexiglass shields for testing sites, comfortable face shields for clinical providers, affordable oversized breath shields for ophthalmology and 3D printed flip-up attachments to the safety goggles for nurses.

The Children’s National Hospital innovation working group shares a retrospective on their local experience in mobilizing resources to offer relief following the personal protective equipment (PPE) shortages at the beginning of COVID-19. Engineers and clinicians developed plexiglass shields for testing sites, comfortable face shields for clinical providers, affordable oversized breath shields for ophthalmology and 3D printed flip-up attachments to the safety goggles for nurses.

The study, published in the Surgical Innovation Journal, narrates a series of events that occurred at the beginning of the pandemic, where the increased demand for personal protective equipment (PPE) usage in healthcare personnel skyrocketed and led to a severe national shortage. Still, the multidisciplinary approach at Children’s National facilitated the response and preparedness to the emerging situation back in March of 2020, serving as a framework for the current and future challenges.

To meet the needs of one of the busiest pediatric emergency departments in the country, the researchers aimed to develop a plexiglass shield that was reliable, reusable and practical while staying pediatric-friendly. The prototype had advantages and disadvantages while administering a COVID-19 swab test in a tent.

The 2020 FDA Emergency Authorization Use (EUA) issued in April provided manufacturing guidelines to produce face shields. Given the federal support, innovators at Children’s National, in partnership with GCMI, designed a rigid and foam prototype. Both prototypes were measured by comfort, visibility, breathability, ability to perform the job, durability, stability, fit and easy assembly. The rigid prototype performed the highest in all metrics and it had few adjustments after various tests.

“While the FDA has become nimbler as evidenced by rapid issuance of EUA of the vaccines, regulatory concerns are still paramount,” Operfmann et al. write. “Having staff experienced with regulatory processes is important to introduce new regulated devices.”

In May 2020, there was also a production lag on the available oversized breath shields for ophthalmology slits, which cost between $35 and $40. To lift the burden, the researchers designed and produced in-house a cost-effective oversized breath shield for less than $9. They used a 40 W laser machine to cut through the thick clear cast acrylic while following the compatible measurements of commercial lamps. The team also distributed the breath shields to other Children’s National regional clinics.

Within the nursing staff, the main factor associated with abiding to PPE compliance is the usage of safety goggles before entering a room. But in time-sensitive situations like patients with severe COVID-19 symptoms, the equipment can be easily forgotten. To support busy shifts, researchers designed a 3D printable attachment valued at $5 for safety goggles, which are more comfortable to keep on, even during downtime. The efficacy of the flip-up attachment is yet to be determined in an upcoming trial.

“Hospitals have already begun augmenting their disaster preparation plans and ensuring they have adequate stockpiles of equipment for future events,” Opfermann et al. write.

Children’s National authors on the study include: Justin Opfermann, M.S., Anuradha Dayal, M.D.Alyssa Abo, M.D., M.B.A., Tyler Salvador, B.S., Kolaleh Eskandanian, Ph.D., M.B.A., P.M.P., Raven McLeese, R.N., and Kevin R. Cleary, Ph.D.

illustration of lungs with coronavirus inside

Pediatric asthma exacerbations during the COVID-19 pandemic

illustration of lungs with coronavirus inside

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years.

In the United States, pediatric asthma exacerbations typically peak in the fall due to seasonal factors such as increased spread of common respiratory viruses, increased exposure to indoor aeroallergens, changing outdoor aeroallergen exposures and colder weather. In early 2020, measures enacted to reduce spread of the coronavirus (COVID-19) — such as social distancing, quarantines and school closures — also reduced pediatric respiratory illnesses and asthma morbidity. Children’s National Hospital immunologist and allergist William J. Sheehan, M.D., and colleagues sought to determine if these measures also affected the 2020 fall seasonal asthma exacerbation peak in Washington, D.C.

The authors found that in 2020, the District of Columbia did not experience the typical “September asthma epidemic” of exacerbations seen in past years. Emergency department visits, hospitalizations and intensive care unit admissions for asthma during the 2020 fall season were significantly reduced compared to previous years.

The authors conclude that, “this is likely due to social distancing, quarantines and school closures enacted during the pandemic. This is a small silver lining in a very difficult year. As 2021 brings optimism for gradual improvements of the pandemic, careful monitoring is necessary to recognize and prepare for childhood asthma morbidity to return to pre-pandemic levels.”

Additional study authors include: Shilpa J. Patel, M.D., M.P.H., Rachel H.F. Margolis, Ph.D., Eduardo R. Fox, M.D., Deborah Q. Shelef, M.P.H., Nikita Kachroo, B.S., Dinesh Pillai, M.D. and Stephen J. Teach, M.D., M.P.H.

Read the full study in the Journal of Allergy and Clinical Immunology: In Practice.

Asthma-Related Healthcare Utilization by Month

Asthma-Related Healthcare Utilization by Month (2016-2020). Asthma-related emergency department (ED) visits, hospitalizations and pediatric intensive care unit (PICU) admissions over time by month between 2016 and 2020. The p-values are for comparisons of mean monthly numbers for fall seasons of 2016-2019 to fall season of 2020. Image courtesy of the Journal of Allergy and Clinical Immunology: In Practice.

child receiving COVID test

COVID testing results highlight importance of understanding virus in children

child receiving COVID test

A new study looking at the results of testing children for COVID-19 through a Children’s National Hospital community-based testing site found that one in four patients had a positive test.

A new study looking at the results of testing children for COVID-19 through a Children’s National Hospital community-based testing site found that one in four patients had a positive test. The findings, reported online Dec. 18 in The Journal of Pediatrics, reinforce that children and young adults are impacted by the virus more than originally believed, and that the continued understanding of their role in transmitting COVID-19 is essential to getting the virus under control.

Of the 1,445 patients tested at the specimen collection site for SARS-CoV-2 virus between March 21 and May 16, 2020, the median age was 8 years old, and more than 34% of positive patients were Hispanic, followed by non-Hispanic Black and non-Hispanic white. The daily positivity rate increased over the study period, from 5.4% during the first week to a peak of 47.4% in May. Children and adolescents were referred to the testing site because of risk of exposure or mild symptoms.

“We knew that community-based testing sites were key in minimizing exposure risk to other patients and health care workers, preserving PPE, centralizing specimen collection services, mitigating acute care site overcrowding and informing our community of the burden caused by this disease,” says Joelle Simpson, M.D., medical director of Emergency Preparedness at Children’s National.

Drive-through/walk-up testing sites outside of a traditional acute care setting have emerged around the world to meet the need for testing mildly ill or asymptomatic individuals. In March, Children’s National Hospital opened a drive-up/walk-up location — one of the first exclusively pediatric testing sites for the virus in the U.S. — where primary care doctors in the Washington, D.C., region could refer young patients for COVID-19 specimen collection and testing.

“At first, children were not the target of testing initiatives, but it is clear that making testing available to pediatric patients early was a very important part of the pandemic response,” says Meghan Delaney, D.O., M.P.H., chief of Pathology and Laboratory Medicine at Children’s National. “Not only can children get severe disease, they can be part of positive clusters with the adults they live with. The knowledge we have gained by testing many thousands of children over the pandemic has provided key information.”

Compared with non-Hispanic white children and after adjustments for age, sex and distance of residence from specimen collection site, minority children had a higher likelihood of infection.

“We wanted to identify the features of children tested at this site who did not require acute medical care and be able to compare demographic and clinical differences between patients who tested positive and negative for COVID-19,” says Dr. Simpson.

Patients with COVID-19 exposure and symptoms were more likely to have a positive test than patients without symptoms. This supports contact tracing for symptomatic cases and testing as an important tool in detecting and containing community spread, according to the study’s findings. Although most patients were referred because they lived with a family member with high risk for exposure or infection, this was not associated with positive test results.

“The impact of this virus is broad and affects planning for children, especially as schools and childcare centers work to reopen,” Dr. Simpson says. “In order to guide the development of measures to control the ongoing pandemic, we need better understand the transmission potential of these mildly symptomatic or well children and young adults.”

COVID-19 triage tent outside the hospital Emergency Department

Telehealth team shares its pandemic response and discusses the future of telehealth

COVID-19 triage tent outside the hospital Emergency Department

The telehealth team at Children’s National Hospital is featured in DataBank IMX’s latest Tech Talk podcast. They discuss how the organization scaled up and managed the telehealth program through the early and mid phases of the COVID-19 pandemic, as well as the future of telehealth.

Featured in the discussion are clinical, operational and revenue cycle leaders from Children’s National:

  • Mary Daymont, M.S.N., R.N., CCM, Vice President, Revenue Cycle & Care Management
  • Clarence Williams, MHA, MBA, Director, Telehealth Program
  • Alejandro Lopez-Magallon, M.D., Medical Director, Telehealth Program, Cardiac Critical Care Specialist

tech talk

The science-policy interface

We can do better: Lessons learned on COVID-19 data sharing can inform future outbreak preparedness

Since COVID-19 emerged late last year, there’s been an enormous amount of research produced on this novel coronavirus disease. But the content publicly available for this data and the format in which it’s presented lack consistency across different countries’ national public health institutes, greatly limiting its usefulness, Children’s National Hospital scientists report in a new study. Their findings and suggestions, published online August 19 in Science & Diplomacy, could eventually help countries optimize their COVID-19-related data — and data for future outbreaks of other diseases — to help further new research, clinical decisions and policy-making around the world.

Recently, explains study senior author Emmanuèle Délot, Ph.D., research faculty at Children’s National Research Institute, she and her colleagues sought data on sex differences between COVID-19 patients around the world for a new study. However, she says, when they checked the information available about different countries, they found a startling lack of consistency, not only for sex-disaggregated data, but also for any type of clinical or demographic information.

“The prospects of finding the same types of formats that would allow us to aggregate information, or even the same types of information across different sites, was pretty dismal,” says Dr. Délot.

To determine how deep this problem ran, she and colleagues at Children’s National, including Eric Vilain, M.D., Ph.D., the James A. Clark Distinguished Professor of Molecular Genetics and the director of the Center for Genetic Medicine Research at Children’s National, and Jonathan LoTempio, a doctoral candidate in a joint program with Children’s National and George Washington University, surveyed and analyzed the data on COVID-19.

The research spanned data reported by public health agencies from highly COVID-19 burdened countries, viral genome sequence data sharing efforts, and data presented in publications and preprints.

PubMed entries with coronavirus

Publications with the term “coronavirus” archived in PubMed over time.

At the time of study, the 15 countries with the highest COVID-19 burden at the time included the US, Spain, Italy, France, Germany, the United Kingdom, Turkey, Iran, China, Russia, Brazil, Belgium, Canada, the Netherlands and Switzerland. Together, these countries represented more than 75% of the reported global cases. The research team combed through COVID-19 data presented on each country’s public health institute website, looking first at the dashboards many provided for a quick glimpse into key data, then did a deeper dive into other data on this disease presented in other ways.

The data content they found, says LoTempio, was extremely heterogeneous. For example, while most countries kept running totals on confirmed cases and deaths, the availability of other types of data — such as the number of tests run, clinical aspects of the disease such as comorbidities, symptoms, or admission to intensive care, or demographic information on patients, such as age or sex — differed widely among countries.

Similarly, the format in which data was presented lacked any consistency among these institutes. Among the 15 countries, data was presented in plain text, HTML or PDF. Eleven offered an interactive web-based data dashboard, and seven had comma-separated data available for download. These formats aren’t compatible with each other, LoTempio explains, and there was little to no documentation about where the data that supplies some formats — such as continually updated web-based dashboards — was archived.

The science-policy interface

Graphic representation of the science-policy interface.

Dr. Vilain says that a robust system is already in place to allow uniform sharing of data on flu genomes — the World Health Organization’s (WHO) Global Initiative on Sharing All Influenza Data (GISAID) — which has been readily adapted for the virus that causes COVID-19 and has already helped advance some types of research. However, he says, countries need to work together to develop a similar system for harmonized sharing other types of data for COVID-19. The study authors recommend that COVID-19 data should be shared among countries using a standardized format and standardized content, informed by the success of GISAID and under the backing of the WHO.

In addition, the authors say, the explosion of research on COVID-19 should be curated by experts who can wade through the thousands of papers published on this disease since the pandemic began to identify research of merit and help merge clinical and basic science.

“Identifying the most useful science and sharing it in a way that’s usable to most researchers, clinicians and policymakers, will not only help us emerge from COVID-19 but could help us prepare for the next pandemic,” Dr. Vilain says.

Other researchers who contributed to this study include D’Andre Spencer, MPH, Rebecca Yarvitz, BA, and Arthur Delot-Vilain.

NCC-PDI-COVID19-Edition-Competition

NCC-PDI launches special pediatric medical device competition focused on covid-19 innovations

Kolaleh-Eskandanian

“Innovation in children’s medical devices consistently lags behind that of adults and we need to change that if we are to confront the challenge to children’s health of COVID-19 and future pandemics,” said Kolaleh Eskandanian, Ph.D., MBA, PMP, vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. 

As medical data increasingly highlights the serious impact of COVID-19 on children’s health, the National Capital Consortium for Pediatric Device Innovation (NCC-PDI) announces a special pitch competition focused on COVID-19-related pediatric medical devices that support home health monitoring and telehealth, and improve sustainability, resiliency and readiness in diagnosing and treating children during a pandemic.

The “Make Your Medical Device Pitch for Kids!” COVID19 edition is led by NCC-PDI co-founders the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Hospital and the A. James Clark School of Engineering at the University of Maryland and powered by nonprofit accelerator and NCC-PDI member, MedTech Innovator. The finals in the virtual pitch event will be held on July 20, 2020. Winners will each receive a grant award of up to $50,000.

“Despite early reports that COVID-19 posed less of a threat to children, a recent study published by Children’s National shows that considerable numbers of pediatric patients are hospitalized and become critically ill from the disease,” said Kolaleh Eskandanian, Ph.D., MBA, PMP, vice president and chief innovation officer at Children’s National Hospital and principal investigator of NCC-PDI. “Innovation in children’s medical devices consistently lags behind that of adults and we need to change that if we are to confront the challenge to children’s health of COVID-19 and future pandemics.”

Funding for the competition is made possible by a grant from the Food and Drug Administration (FDA) and a philanthropic gift from Mei Xu, founder of e-commerce platform Yes She May, a site dedicated to women-owned brands.

Along with grant funding, one company from the competition will be selected by Johnson & Johnson Innovation – JLABS to receive a one-year residency at JLABS @ Washington, DC, which will be located on the new Children’s National Research & Innovation Campus currently under construction. In addition to the 2021 JLABS residency, the awardee will have access to the JLABS community and expert mentoring by the Johnson & Johnson family of companies.

Submissions for the competition are being accepted now through Monday, July 6, 2020z at the NCC-PDI website, Innovate4Kids.org, where complete details can be found.

NCC-PDI is one of five members in the FDA’s Pediatric Device Consortia Grant Program created to support the development and commercialization of medical devices for children, which lags significantly behind the progress of adult medical devices. Along with Children’s National, University of Maryland and Medtech Innovator, NCC-PDI members include accelerator BioHealth Innovation and design firm Archimedic.

To date, NCC-PDI has mentored over 100 medical device sponsors to help advance their pediatric innovations, with seven devices having received either their FDA market clearance or CE marking. The consortium hosts a major pediatric pitch competition annually that showcases and awards promising pediatric innovations and provides a first-of-its-kind pediatric-focused accelerator program for finalists.

NCC-PDI-COVID19-Edition-Competition