Pediatrics

From Wayne State University, Detroit, MI (Dr. Gibson-Scipio), and the University of Texas Rio Grande Valley, Edinburg, TX (Dr. Krouse).

Abstract

• Objective: To review the literature on barriers to asthma self-management among African American adolescents.
• Methods: Review of the literature.
• Results: Asthma self-management barriers experienced by African American adolescents are often related to developmental needs, lack of knowledge, and personal perspectives and experiences. Adolescents find managing their symptoms and adhering to prescriptive therapies a burden and desire to be more like healthy peers. As they struggle to identify with peers, they may engage in risky behaviors such as ignoring symptoms and delaying treatment, thus leading to poorer asthma control and health outcomes. African American adolescents struggle with perceptions of racial biases from health care providers and teachers that interfere with self-management behaviors. They also describe the influence of culturally based practices learned from caregivers that contribute to their misconceptions and inadequate skills in effectively managing their asthma.
• Conclusion: Researchers should seek to develop interventions to address the unique contextual and culturally based needs of African American adolescents that support the development of effective asthma self-management behaviors. This may include making use of family members (especially mothers) and extended support for self-management during this period of rapid growth and transition. Health care providers should consider a team-based approach to the adolescent patient. Such an approach should be grounded in recommendations from national guidelines that suggest a patient-centered approach to care that includes a partnership between the patient and the provider to address unique barriers to effective self-management.

Keywords: youth; caregiver; drug-therapy; self-efficacy; disease-management; patient-centered care.

Effective asthma self-management by urban African American adolescents is a critical aspect of care that should be addressed with vigilance due to the persistent disparities in disease prevalence, morbidity, and mortality compared to Caucasians.^1-3 The overarching goal of asthma self-management is to achieve symptom control, maintain normal activity levels, and minimize future risk of exacerbations and medication side effects.^4,5 Best practices for asthma self-management begin with a partnership between health care providers and clients (including parent/caregiver). This relationship should help affected individuals gain asthma control based on knowledge of their disease and treatment options, confidence and skills in trigger avoidance, medication administration, and management of acute exacerbations.^4,5

Among youth aged 18 years and younger, African Americans have the highest asthma prevalence rates of all racial and ethnic groups, and between 2001 and 2009 asthma prevalence rates rose by 50% among African American youth.⁶ As of 2015, prevalence rates for asthma among African American youth were 13.4%, as compared to 7.4% for white youth.⁷ African American youth have been found to have more frequent asthma exacerbations and related school absences than white youth.⁸ Furthermore, African American youth younger than 18 years are more likely to be admitted to the hospital for asthma and are 10 times more likely to die from asthma compared to non-Hispanic white children.⁶

Urban African American adolescents with asthma are particularly vulnerable to poor asthma self-management due to the complexity of the disease in this population.³ African American youth must deal with multiple adverse environmental conditions, lack of knowledge or disbelief concerning effective disease self-management strategies, variable access and quality of care, and the psychosocial dynamics of being young while having a chronic disease.^2,3,9-11 It is important to understand and address barriers to successful asthma self-management during adolescence, as behaviors developed during this stage of life often persist into adulthood.⁹ In this article, we review the literature on barriers to asthma self-management among African American adolescents and offer suggestions on clinical strategies for improving self-management in this vulnerable population.

 

 

Methods

The initial search strategy was developed in collaboration with an experienced librarian. Keywords, MeSH terms, and potential databases were identified. Keywords included urban, African American, adolescent, asthma, self-management, and barriers. These terms were expanded based on search results and a review of abstracts that fit the intent of our review. The search was limited to U.S. studies published between 2005 and 2017. Excluded from the search were conference abstracts, doctoral dissertations, master’s theses, meta-analyses, systematic reviews, and studies conducted outside of the United States. Additional articles for the review were identified during the review process from the reference lists of the publications.

Abstracts were reviewed for articles that reported a study population inclusive of African American adolescents with asthma and that were related to self-management. Studies that used qualitative and other descriptive methods and cohort and randomized control trials were reviewed. Due to the limited number of articles found that exclusively focused on African Americans, the authors set a threshold for African American participants at 40% or greater for inclusion in this review.

Full papers were retrieved that met the inclusion criteria for a full review. Each author initially independently reviewed a selected number of papers and abstracted the study purpose, sample, study design, results, conclusions, and limitations. Subsequently, both authors reviewed in tandem and then discussed each selected manuscript to assure the appropriateness for inclusion. The subject matter was considered the priority for inclusion in the review. Study methods, sample size, and noted limitations were categorized but were not considered as a basis for exclusion. Thematic analysis was used to identify common themes across studies.

 

 

Results

We identified 23 papers that met our criteria (Table). Five common themes were found that related to barriers in disease self-management for African American adolescents: (a) knowledge and skills, (b) beliefs and attitudes, (c) personal/emotional factors, (d) caregivers, and (e) schools.

 

 

Knowledge and Skills

Adequate knowledge of the elements of asthma self-management is critical for achieving control of this condition. Asthma knowledge includes a basic understanding of the disease process and treatment strategies, an awareness of early signs and symptoms of worsening asthma, and an understanding of how to manage environmental triggers.^4,5 Sin and colleagues conducted one of the earlier studies to examine the influence of asthma knowledge on asthma self-management in African American adolescents and found a significant positive association between knowledge and asthma self-management behaviors.¹²

Adherence to an asthma medication, especially inhaled corticosteroids (ICS), is one of the cornerstones to successful self-management of asthma.^13,14 Consistent use of ICS therapy to control asthma symptoms and disease progression is often suboptimal in African American adolescents and tends to worsen as they age;¹⁵ studies have found lower adherence levels were more prominent in older African American adolescents and males.^13,16 In a recent study of adolescents with persistent asthma who were prescribed daily ICS, youth with greater ICS knowledge as assessed using a standardized instrument demonstrated significantly higher adherence rates.¹³ Proper technique in the use of an inhaler is also important in medication administration. Asthma ICS medication delivery devices vary significantly and require different techniques for medication administration. However, inhaler device skills have been found to be very inadequate in high-risk African American adolescents.¹⁷ Thus, knowledge related to ICS therapy and proper skills in the use of inhaler devices is an important aspect of asthma self-management that have been found to be inadequate in African American Adolescents.

Interventions and programs geared to improving education may lead to improved self-management. Multisystemic Therapy-Health Care (MST-HC) is a tailored home-based intervention that includes knowledge and skill-building components. In a study of African American youth with poorly controlled asthma, the program was found to improve illness management.¹⁸ In addition, adolescents who complete formal asthma education programs demonstrate significantly higher scores in self-management than those youth who do not participate in these programs.^13,19 Unfortunately, few African American teens report participation in an asthma education program.¹⁹ In a study of a motivational interviewing intervention to improve controller medication adherence for African American adolescents,¹⁴ youth reported gaining more knowledge about their asthma medications and were significantly more motivated to take their controller medications after participating in the intervention; however, while adherence to controller medications was greater than baseline, it was not significantly different.¹⁴ This study demonstrated the value of asthma education and the feasibility of a motivational intervention to support controller medication adherence. However, this study also demonstrated the complexity of medication adherence in that neither knowledge or motivation led to significant changes in medication adherence among African American adolescents.

Low health literacy can also act as a barrier to asthma self-management. Health literacy requires skills and knowledge that enable an individual to communicate, process, and understand basic health information that informs health decisions.²⁰ Health literacy was found to be associated with indicators of poor disease self-management among urban African American adolescents in grades 9 through 12.²¹ In this study, health literacy was established using questions about confidence in filling out medical forms, self-reported problems with learning about the youth’s medical condition, and the need for assistance in reading hospital materials. Adolescents with poor health literacy scores were more likely to reside in a household with the following characteristics: mother with less than a high school education, Medicaid health insurance, family members with a body mass index exceeding the 85th percentile, and lack of rescue medication. Poor health literacy was most common among younger adolescents (ie, ninth graders). Some youth with poor health literacy also reported more emergency department visits, hospitalizations, and lower overall quality of life.²¹

Beliefs and Attitudes

Beliefs and attitudes towards taking asthma medications can act as barriers to adherence in the adolescent. African American adolescents often report the belief that ICS are not helpful or necessary.^16,22-25 These beliefs have been correlated with a lack of understanding of the inflammatory mechanisms of asthma, reports of asthma attacks despite use of controller medications, fear of addiction to medications, and a belief that nontraditional interventions (eg, exercise) will work better to get rid of asthma or abate symptoms.^16-19,22-24 African American adolescents also report beliefs that asthma will go away or get better as they age, and they are willing to forgo the use of controller medications based on these beliefs.²⁴

African American adolescents often engage in asthma self-management independent of caregivers. These youth describe asthma self-management activities an annoyance and of low priority in part due to competing tasks and negative interactions with caregivers.²⁵ During early adolescence asthma self-management is often suboptimal, and as youth age they become less observant regarding their asthma and are less likely to seek help.²⁶ Adolescents’ beliefs and low prioritization of asthma self-management may contribute to forgetfulness and loss of inhalers, which are common reasons reported for poor adherence to ICS.^16,23-26 Further, the role of caregivers during this period has often been overlooked. Caregivers of African American adolescents have been found to be stressed and overwhelmed with personal responsibilities and neighborhood conditions, leaving them little time to attend to the asthma self-management behavior of youth. Due to these contextual factors, interactions with chronically ill youth may be strained, resulting in negative interactions with youth related to asthma self-management. However, in an intervention study that used multisystemic therapy (an approach that targets the affected individual, family, and community), improvement in positive parenting behaviors related to asthma self-management contributed to improved ICS adherence by adolescents.²⁷

Adolescents can perceive traditional asthma self-management as conflicting with their own personal and/or cultural beliefs. They may seek options beyond the use of medicine and have voiced preferences for behaviors that they believe will “strengthen their lungs” more naturally.²⁴ An appreciation of how youth might use complementary/alternative medicine (CAM) as an adjunctive therapy or in place of evidence-based asthma care is important to understanding the potential effect on morbidity and mortality. Behaviors and beliefs about the use of CAM have not been well studied among urban African American adolescents with asthma. Only one study was found that assessed the use of CAM among a primarily urban African American adolescent population. In that study, 71% of the population reported using some form of CAM during the past 30 days.²⁸ Prayer and relaxation were the most frequently used strategies in the management of asthma symptoms. Perceived efficacy of relaxation and prayer among teens who engaged in this form of CAM was 87% and 85%, respectively. Other CAM strategies included yoga, meditation, guided imagery, and biofeedback. When adolescents were asked if they shared their use of CAM in asthma management with a health care provider, most reported sharing the use of yoga and dietary changes but were least likely to share their use of prayer and guided imagery.²⁸

Personal/Emotional Factors

African American adolescents have reported asthma as a limiting factor in terms of both physical and social activities. They perceive asthma as a burden to themselves and others (eg, peers, family, coaches).^9,25 The burden of asthma is further exemplified in the emotional response to the symptoms of the disease and the self-management responsibilities. The need to prevent and respond to asthma symptoms is associated with being embarrassed, frustrated, angry, annoyed, worried, lonely, and isolated.^9,11,25 Negative coping strategies by youth in response to psychosocial experiences include decisions to disregard or give minimal attention to asthma symptoms and to delay or not take prescribed medications. Students report ignoring asthma symptom management while engaging in physical activities to maintain a sense of normalcy among peers and as a way of dealing with perceptions by coaches or teachers that they are weak or in need of being protected.^24,25

Negative thoughts and experiences can result in depressive disorders and poor quality of life. Depression is a common finding among urban youth with asthma.^29,30 Youth diagnosed with asthma who have comorbid depression may benefit from interventions to improve self-management. In a secondary analysis from a Web-based asthma management intervention targeting African American adolescents, depression was found to have a modifying effect on the emotional domain of quality of life for youth in the intervention arm of the study. This finding indicates that participants who were depressed and who reported low levels of emotional quality of life benefited from the Web-based interventions that targeted self-management.³¹

Caregivers

Caregivers (especially moms) are a common source of support for the development and implementation of asthma self-management behaviors in adolescents.³² Caregivers sometimes hold beliefs similar to those of youth and believe the urban environment can act as a barrier to asthma management.^9,25,32 They describe the complexity of asthma treatment plans, a lack of understanding of the disease process, and insensitivity of health care providers to their expressed needs along with the providers’ limited cultural awareness in the development of self-management plans.^9,22,33 Caregivers describe how family finances, insurance gaps, access to care, and their own familial/cultural beliefs influence their decisions and ability to support their child’s asthma management.³³ When faced with the cost of care they report instances of having to decide between necessities such as food and housing or co-pays for medications and office visits.^22,33 They also report concerns about visits with multiple providers due to an inability to access their primary care provider, which can lead to delays in their child being diagnosed with asthma.²²

Caregivers report a need to include culturally based practices, past experiences, and personal beliefs into the adolescents’ asthma management plan.^22,32,33 In a small interview-based study of caregivers residing in 3 New Jersey public housing communities, caregivers reported preferring “familial” methods of controlling asthma (eg, restriction of activities; use of showers, steam, vaporizers, and nebulizers) over evidence-based recommendations. Many caregivers were confused or lacked knowledge about asthma action plans.³³ Caregivers have also been found to lack adequate or accurate knowledge related to asthma medications and factors that improved or worsened asthma. While caregivers report a desire to help educate their teens by passing on what they know, their lack of adequate asthma knowledge may hamper their efforts and potentially worsen the teens’ asthma self-management.³²

While African American caregivers often describe themselves as hypervigilant concerning their child’s asthma, they may report different information than their adolescent when both are questioned about asthma symptom experiences and functional status.³⁴ Factors increasing the level of congruence between caregiver and teen asthma symptom reports were found to be related to the adolescents’ age and asthma disease classification. Symptom questionnaire responses of older teens and those with mild intermittent asthma were more likely to be similar to caregiver reports. The researchers concluded that clinicians and researchers may obtain reliable asthma symptom and functional status reports by asking the adolescent directly.³⁴

Schools

Caregivers and adolescents describe schools as a threat to self-management and the overall health of youth with asthma.^9,32 They perceive that a lack of knowledge by staff, teachers, and coaches contributes to inattentiveness or disbelief in the credibility of reported asthma symptoms by youth.^11,23 These misperceptions and the lack of attentiveness by adults in the school may pose safety and health issues for African American youth.^9,25,33,34 For example, adolescents report pressure from teacher, coaches, and peers in school settings to partake in sports and/or gym classes. Youth want to identify with healthy peers and thus often choose not to take asthma medications during such activities or opt to continue participating while being compromised by airway obstruction. Of great concern were reports by caregivers and teens of not being allowed to call a parent for support or retrieve their medications when needed for asthma symptoms.³²

Future Research and Practice Implications

In this review, we identified 5 common themes around barriers to asthma self-management for African American adolescents (knowledge and skills, beliefs and attitudes, personal/emotional factors, caregivers, and schools). Caregivers, especially mothers, play a pivotal role in the development of effective asthma self-management behaviors. Depsite good intentions, there is evidence of caregivers passing on ineffective experiential and culturally based beliefs and practices to their adolescents that can negatively influence self-care behaviors.^13,28,38 Studies are needed to further investigate these findings among caregivers as their beliefs and practices for asthma self-management have been found to coexist among adolescents. Studies that investigate how to incorporate caregiver asthma knowledge, cultural beliefs and behaviors in developing self-management interventions have the potential to positively influence asthma outcomes among African American adolescents.²⁷ The unique cultural beliefs, contextual environmental, and social disparities faced by African American caregivers should not be neglected.

African American adolescents, like adolescents in other racial or ethnic groups, desire to be autonomous in their asthma self-management. However, as adolescents age their adherence behaviors often decline. This may suggest a need for a longer transition period to self-management that extends into emerging adulthood (18-25 years). While youth want to feel supported, there appears to be a fine line between receiving needed support and what youth describe as “nagging” behaviors by adults. Additional investigations into how asthma responsibilities are transitioned from the parent to youth and how best to support the development and maintenance of related behaviors and skills are warranted. In addition, teens described problems related to communicating with health care providers, noting a lack of clarity in explanations received about how to manage their asthma. Some teens believed the communication challenges were based on beliefs and biases held by providers that African American youth had limited capacities for self-management.⁹ There is a need to better understand interactions among African American adolescents, parents, and clinicians so that communication and transitioning asthma care to the youth will produce optimal health outcomes.

According to asthma guidelines, the patient-provider relationship is essential to effective asthma self-management.^4,5 However, there is little mention in the literature of team-based care. Clinicians such as physicians, physician assistants, and nurse practitioners provide direct care to adolescents in terms of disease management and the overall effectiveness of treatment plans. African American youth demonstrate a need for asthma education that is comprehensive and that is contextualized to their daily lives. A team-based approach to care that includes social workers and community health workers may help to extend the reach of clinicians. Follow-up times with families and youth between office visits can be used to support adolescents to develop asthma self-management and allow them a safe space to describe frustrations and other emotions that contribute to their desire to be disease-free.

Summary

Asthma is a chronic disease that is often more severe and difficult to manage in African American adolescents. While African American adolescents describe developmental needs like those of other youth, cultural beliefs and contextual experiences influence their self-care management in unique ways. Opportunities exist to better understand the needs of African American adolescents and to help them successfully gain the knowledge, skills, and behaviors needed to effectively engage in self-management of their asthma.

Corresponding author: Wanda Gibson-Scipio, PhD, FNP-BC, FAANP, 5557 Cass Ave., 346 Cohn Building, Detroit, MI 48324; gibsonsc@wayne.edu.

Financial disclosures: None.

From Wayne State University, Detroit, MI (Dr. Gibson-Scipio), and the University of Texas Rio Grande Valley, Edinburg, TX (Dr. Krouse).

Abstract

• Objective: To review the literature on barriers to asthma self-management among African American adolescents.
• Methods: Review of the literature.
• Results: Asthma self-management barriers experienced by African American adolescents are often related to developmental needs, lack of knowledge, and personal perspectives and experiences. Adolescents find managing their symptoms and adhering to prescriptive therapies a burden and desire to be more like healthy peers. As they struggle to identify with peers, they may engage in risky behaviors such as ignoring symptoms and delaying treatment, thus leading to poorer asthma control and health outcomes. African American adolescents struggle with perceptions of racial biases from health care providers and teachers that interfere with self-management behaviors. They also describe the influence of culturally based practices learned from caregivers that contribute to their misconceptions and inadequate skills in effectively managing their asthma.
• Conclusion: Researchers should seek to develop interventions to address the unique contextual and culturally based needs of African American adolescents that support the development of effective asthma self-management behaviors. This may include making use of family members (especially mothers) and extended support for self-management during this period of rapid growth and transition. Health care providers should consider a team-based approach to the adolescent patient. Such an approach should be grounded in recommendations from national guidelines that suggest a patient-centered approach to care that includes a partnership between the patient and the provider to address unique barriers to effective self-management.

Keywords: youth; caregiver; drug-therapy; self-efficacy; disease-management; patient-centered care.

Effective asthma self-management by urban African American adolescents is a critical aspect of care that should be addressed with vigilance due to the persistent disparities in disease prevalence, morbidity, and mortality compared to Caucasians.^1-3 The overarching goal of asthma self-management is to achieve symptom control, maintain normal activity levels, and minimize future risk of exacerbations and medication side effects.^4,5 Best practices for asthma self-management begin with a partnership between health care providers and clients (including parent/caregiver). This relationship should help affected individuals gain asthma control based on knowledge of their disease and treatment options, confidence and skills in trigger avoidance, medication administration, and management of acute exacerbations.^4,5

Among youth aged 18 years and younger, African Americans have the highest asthma prevalence rates of all racial and ethnic groups, and between 2001 and 2009 asthma prevalence rates rose by 50% among African American youth.⁶ As of 2015, prevalence rates for asthma among African American youth were 13.4%, as compared to 7.4% for white youth.⁷ African American youth have been found to have more frequent asthma exacerbations and related school absences than white youth.⁸ Furthermore, African American youth younger than 18 years are more likely to be admitted to the hospital for asthma and are 10 times more likely to die from asthma compared to non-Hispanic white children.⁶

Urban African American adolescents with asthma are particularly vulnerable to poor asthma self-management due to the complexity of the disease in this population.³ African American youth must deal with multiple adverse environmental conditions, lack of knowledge or disbelief concerning effective disease self-management strategies, variable access and quality of care, and the psychosocial dynamics of being young while having a chronic disease.^2,3,9-11 It is important to understand and address barriers to successful asthma self-management during adolescence, as behaviors developed during this stage of life often persist into adulthood.⁹ In this article, we review the literature on barriers to asthma self-management among African American adolescents and offer suggestions on clinical strategies for improving self-management in this vulnerable population.

 

 

Methods

The initial search strategy was developed in collaboration with an experienced librarian. Keywords, MeSH terms, and potential databases were identified. Keywords included urban, African American, adolescent, asthma, self-management, and barriers. These terms were expanded based on search results and a review of abstracts that fit the intent of our review. The search was limited to U.S. studies published between 2005 and 2017. Excluded from the search were conference abstracts, doctoral dissertations, master’s theses, meta-analyses, systematic reviews, and studies conducted outside of the United States. Additional articles for the review were identified during the review process from the reference lists of the publications.

Abstracts were reviewed for articles that reported a study population inclusive of African American adolescents with asthma and that were related to self-management. Studies that used qualitative and other descriptive methods and cohort and randomized control trials were reviewed. Due to the limited number of articles found that exclusively focused on African Americans, the authors set a threshold for African American participants at 40% or greater for inclusion in this review.

Full papers were retrieved that met the inclusion criteria for a full review. Each author initially independently reviewed a selected number of papers and abstracted the study purpose, sample, study design, results, conclusions, and limitations. Subsequently, both authors reviewed in tandem and then discussed each selected manuscript to assure the appropriateness for inclusion. The subject matter was considered the priority for inclusion in the review. Study methods, sample size, and noted limitations were categorized but were not considered as a basis for exclusion. Thematic analysis was used to identify common themes across studies.

 

 

Results

We identified 23 papers that met our criteria (Table). Five common themes were found that related to barriers in disease self-management for African American adolescents: (a) knowledge and skills, (b) beliefs and attitudes, (c) personal/emotional factors, (d) caregivers, and (e) schools.

 

 

Knowledge and Skills

Adequate knowledge of the elements of asthma self-management is critical for achieving control of this condition. Asthma knowledge includes a basic understanding of the disease process and treatment strategies, an awareness of early signs and symptoms of worsening asthma, and an understanding of how to manage environmental triggers.^4,5 Sin and colleagues conducted one of the earlier studies to examine the influence of asthma knowledge on asthma self-management in African American adolescents and found a significant positive association between knowledge and asthma self-management behaviors.¹²

Adherence to an asthma medication, especially inhaled corticosteroids (ICS), is one of the cornerstones to successful self-management of asthma.^13,14 Consistent use of ICS therapy to control asthma symptoms and disease progression is often suboptimal in African American adolescents and tends to worsen as they age;¹⁵ studies have found lower adherence levels were more prominent in older African American adolescents and males.^13,16 In a recent study of adolescents with persistent asthma who were prescribed daily ICS, youth with greater ICS knowledge as assessed using a standardized instrument demonstrated significantly higher adherence rates.¹³ Proper technique in the use of an inhaler is also important in medication administration. Asthma ICS medication delivery devices vary significantly and require different techniques for medication administration. However, inhaler device skills have been found to be very inadequate in high-risk African American adolescents.¹⁷ Thus, knowledge related to ICS therapy and proper skills in the use of inhaler devices is an important aspect of asthma self-management that have been found to be inadequate in African American Adolescents.

Interventions and programs geared to improving education may lead to improved self-management. Multisystemic Therapy-Health Care (MST-HC) is a tailored home-based intervention that includes knowledge and skill-building components. In a study of African American youth with poorly controlled asthma, the program was found to improve illness management.¹⁸ In addition, adolescents who complete formal asthma education programs demonstrate significantly higher scores in self-management than those youth who do not participate in these programs.^13,19 Unfortunately, few African American teens report participation in an asthma education program.¹⁹ In a study of a motivational interviewing intervention to improve controller medication adherence for African American adolescents,¹⁴ youth reported gaining more knowledge about their asthma medications and were significantly more motivated to take their controller medications after participating in the intervention; however, while adherence to controller medications was greater than baseline, it was not significantly different.¹⁴ This study demonstrated the value of asthma education and the feasibility of a motivational intervention to support controller medication adherence. However, this study also demonstrated the complexity of medication adherence in that neither knowledge or motivation led to significant changes in medication adherence among African American adolescents.

Low health literacy can also act as a barrier to asthma self-management. Health literacy requires skills and knowledge that enable an individual to communicate, process, and understand basic health information that informs health decisions.²⁰ Health literacy was found to be associated with indicators of poor disease self-management among urban African American adolescents in grades 9 through 12.²¹ In this study, health literacy was established using questions about confidence in filling out medical forms, self-reported problems with learning about the youth’s medical condition, and the need for assistance in reading hospital materials. Adolescents with poor health literacy scores were more likely to reside in a household with the following characteristics: mother with less than a high school education, Medicaid health insurance, family members with a body mass index exceeding the 85th percentile, and lack of rescue medication. Poor health literacy was most common among younger adolescents (ie, ninth graders). Some youth with poor health literacy also reported more emergency department visits, hospitalizations, and lower overall quality of life.²¹

Beliefs and Attitudes

Beliefs and attitudes towards taking asthma medications can act as barriers to adherence in the adolescent. African American adolescents often report the belief that ICS are not helpful or necessary.^16,22-25 These beliefs have been correlated with a lack of understanding of the inflammatory mechanisms of asthma, reports of asthma attacks despite use of controller medications, fear of addiction to medications, and a belief that nontraditional interventions (eg, exercise) will work better to get rid of asthma or abate symptoms.^16-19,22-24 African American adolescents also report beliefs that asthma will go away or get better as they age, and they are willing to forgo the use of controller medications based on these beliefs.²⁴

African American adolescents often engage in asthma self-management independent of caregivers. These youth describe asthma self-management activities an annoyance and of low priority in part due to competing tasks and negative interactions with caregivers.²⁵ During early adolescence asthma self-management is often suboptimal, and as youth age they become less observant regarding their asthma and are less likely to seek help.²⁶ Adolescents’ beliefs and low prioritization of asthma self-management may contribute to forgetfulness and loss of inhalers, which are common reasons reported for poor adherence to ICS.^16,23-26 Further, the role of caregivers during this period has often been overlooked. Caregivers of African American adolescents have been found to be stressed and overwhelmed with personal responsibilities and neighborhood conditions, leaving them little time to attend to the asthma self-management behavior of youth. Due to these contextual factors, interactions with chronically ill youth may be strained, resulting in negative interactions with youth related to asthma self-management. However, in an intervention study that used multisystemic therapy (an approach that targets the affected individual, family, and community), improvement in positive parenting behaviors related to asthma self-management contributed to improved ICS adherence by adolescents.²⁷

Adolescents can perceive traditional asthma self-management as conflicting with their own personal and/or cultural beliefs. They may seek options beyond the use of medicine and have voiced preferences for behaviors that they believe will “strengthen their lungs” more naturally.²⁴ An appreciation of how youth might use complementary/alternative medicine (CAM) as an adjunctive therapy or in place of evidence-based asthma care is important to understanding the potential effect on morbidity and mortality. Behaviors and beliefs about the use of CAM have not been well studied among urban African American adolescents with asthma. Only one study was found that assessed the use of CAM among a primarily urban African American adolescent population. In that study, 71% of the population reported using some form of CAM during the past 30 days.²⁸ Prayer and relaxation were the most frequently used strategies in the management of asthma symptoms. Perceived efficacy of relaxation and prayer among teens who engaged in this form of CAM was 87% and 85%, respectively. Other CAM strategies included yoga, meditation, guided imagery, and biofeedback. When adolescents were asked if they shared their use of CAM in asthma management with a health care provider, most reported sharing the use of yoga and dietary changes but were least likely to share their use of prayer and guided imagery.²⁸

Personal/Emotional Factors

African American adolescents have reported asthma as a limiting factor in terms of both physical and social activities. They perceive asthma as a burden to themselves and others (eg, peers, family, coaches).^9,25 The burden of asthma is further exemplified in the emotional response to the symptoms of the disease and the self-management responsibilities. The need to prevent and respond to asthma symptoms is associated with being embarrassed, frustrated, angry, annoyed, worried, lonely, and isolated.^9,11,25 Negative coping strategies by youth in response to psychosocial experiences include decisions to disregard or give minimal attention to asthma symptoms and to delay or not take prescribed medications. Students report ignoring asthma symptom management while engaging in physical activities to maintain a sense of normalcy among peers and as a way of dealing with perceptions by coaches or teachers that they are weak or in need of being protected.^24,25

Negative thoughts and experiences can result in depressive disorders and poor quality of life. Depression is a common finding among urban youth with asthma.^29,30 Youth diagnosed with asthma who have comorbid depression may benefit from interventions to improve self-management. In a secondary analysis from a Web-based asthma management intervention targeting African American adolescents, depression was found to have a modifying effect on the emotional domain of quality of life for youth in the intervention arm of the study. This finding indicates that participants who were depressed and who reported low levels of emotional quality of life benefited from the Web-based interventions that targeted self-management.³¹

Caregivers

Caregivers (especially moms) are a common source of support for the development and implementation of asthma self-management behaviors in adolescents.³² Caregivers sometimes hold beliefs similar to those of youth and believe the urban environment can act as a barrier to asthma management.^9,25,32 They describe the complexity of asthma treatment plans, a lack of understanding of the disease process, and insensitivity of health care providers to their expressed needs along with the providers’ limited cultural awareness in the development of self-management plans.^9,22,33 Caregivers describe how family finances, insurance gaps, access to care, and their own familial/cultural beliefs influence their decisions and ability to support their child’s asthma management.³³ When faced with the cost of care they report instances of having to decide between necessities such as food and housing or co-pays for medications and office visits.^22,33 They also report concerns about visits with multiple providers due to an inability to access their primary care provider, which can lead to delays in their child being diagnosed with asthma.²²

Caregivers report a need to include culturally based practices, past experiences, and personal beliefs into the adolescents’ asthma management plan.^22,32,33 In a small interview-based study of caregivers residing in 3 New Jersey public housing communities, caregivers reported preferring “familial” methods of controlling asthma (eg, restriction of activities; use of showers, steam, vaporizers, and nebulizers) over evidence-based recommendations. Many caregivers were confused or lacked knowledge about asthma action plans.³³ Caregivers have also been found to lack adequate or accurate knowledge related to asthma medications and factors that improved or worsened asthma. While caregivers report a desire to help educate their teens by passing on what they know, their lack of adequate asthma knowledge may hamper their efforts and potentially worsen the teens’ asthma self-management.³²

While African American caregivers often describe themselves as hypervigilant concerning their child’s asthma, they may report different information than their adolescent when both are questioned about asthma symptom experiences and functional status.³⁴ Factors increasing the level of congruence between caregiver and teen asthma symptom reports were found to be related to the adolescents’ age and asthma disease classification. Symptom questionnaire responses of older teens and those with mild intermittent asthma were more likely to be similar to caregiver reports. The researchers concluded that clinicians and researchers may obtain reliable asthma symptom and functional status reports by asking the adolescent directly.³⁴

Schools

Caregivers and adolescents describe schools as a threat to self-management and the overall health of youth with asthma.^9,32 They perceive that a lack of knowledge by staff, teachers, and coaches contributes to inattentiveness or disbelief in the credibility of reported asthma symptoms by youth.^11,23 These misperceptions and the lack of attentiveness by adults in the school may pose safety and health issues for African American youth.^9,25,33,34 For example, adolescents report pressure from teacher, coaches, and peers in school settings to partake in sports and/or gym classes. Youth want to identify with healthy peers and thus often choose not to take asthma medications during such activities or opt to continue participating while being compromised by airway obstruction. Of great concern were reports by caregivers and teens of not being allowed to call a parent for support or retrieve their medications when needed for asthma symptoms.³²

Future Research and Practice Implications

In this review, we identified 5 common themes around barriers to asthma self-management for African American adolescents (knowledge and skills, beliefs and attitudes, personal/emotional factors, caregivers, and schools). Caregivers, especially mothers, play a pivotal role in the development of effective asthma self-management behaviors. Depsite good intentions, there is evidence of caregivers passing on ineffective experiential and culturally based beliefs and practices to their adolescents that can negatively influence self-care behaviors.^13,28,38 Studies are needed to further investigate these findings among caregivers as their beliefs and practices for asthma self-management have been found to coexist among adolescents. Studies that investigate how to incorporate caregiver asthma knowledge, cultural beliefs and behaviors in developing self-management interventions have the potential to positively influence asthma outcomes among African American adolescents.²⁷ The unique cultural beliefs, contextual environmental, and social disparities faced by African American caregivers should not be neglected.

African American adolescents, like adolescents in other racial or ethnic groups, desire to be autonomous in their asthma self-management. However, as adolescents age their adherence behaviors often decline. This may suggest a need for a longer transition period to self-management that extends into emerging adulthood (18-25 years). While youth want to feel supported, there appears to be a fine line between receiving needed support and what youth describe as “nagging” behaviors by adults. Additional investigations into how asthma responsibilities are transitioned from the parent to youth and how best to support the development and maintenance of related behaviors and skills are warranted. In addition, teens described problems related to communicating with health care providers, noting a lack of clarity in explanations received about how to manage their asthma. Some teens believed the communication challenges were based on beliefs and biases held by providers that African American youth had limited capacities for self-management.⁹ There is a need to better understand interactions among African American adolescents, parents, and clinicians so that communication and transitioning asthma care to the youth will produce optimal health outcomes.

According to asthma guidelines, the patient-provider relationship is essential to effective asthma self-management.^4,5 However, there is little mention in the literature of team-based care. Clinicians such as physicians, physician assistants, and nurse practitioners provide direct care to adolescents in terms of disease management and the overall effectiveness of treatment plans. African American youth demonstrate a need for asthma education that is comprehensive and that is contextualized to their daily lives. A team-based approach to care that includes social workers and community health workers may help to extend the reach of clinicians. Follow-up times with families and youth between office visits can be used to support adolescents to develop asthma self-management and allow them a safe space to describe frustrations and other emotions that contribute to their desire to be disease-free.

Summary

Asthma is a chronic disease that is often more severe and difficult to manage in African American adolescents. While African American adolescents describe developmental needs like those of other youth, cultural beliefs and contextual experiences influence their self-care management in unique ways. Opportunities exist to better understand the needs of African American adolescents and to help them successfully gain the knowledge, skills, and behaviors needed to effectively engage in self-management of their asthma.

Corresponding author: Wanda Gibson-Scipio, PhD, FNP-BC, FAANP, 5557 Cass Ave., 346 Cohn Building, Detroit, MI 48324; gibsonsc@wayne.edu.

Financial disclosures: None.

From Wayne State University, Detroit, MI (Dr. Gibson-Scipio), and the University of Texas Rio Grande Valley, Edinburg, TX (Dr. Krouse).

Abstract

• Objective: To review the literature on barriers to asthma self-management among African American adolescents.
• Methods: Review of the literature.
• Results: Asthma self-management barriers experienced by African American adolescents are often related to developmental needs, lack of knowledge, and personal perspectives and experiences. Adolescents find managing their symptoms and adhering to prescriptive therapies a burden and desire to be more like healthy peers. As they struggle to identify with peers, they may engage in risky behaviors such as ignoring symptoms and delaying treatment, thus leading to poorer asthma control and health outcomes. African American adolescents struggle with perceptions of racial biases from health care providers and teachers that interfere with self-management behaviors. They also describe the influence of culturally based practices learned from caregivers that contribute to their misconceptions and inadequate skills in effectively managing their asthma.
• Conclusion: Researchers should seek to develop interventions to address the unique contextual and culturally based needs of African American adolescents that support the development of effective asthma self-management behaviors. This may include making use of family members (especially mothers) and extended support for self-management during this period of rapid growth and transition. Health care providers should consider a team-based approach to the adolescent patient. Such an approach should be grounded in recommendations from national guidelines that suggest a patient-centered approach to care that includes a partnership between the patient and the provider to address unique barriers to effective self-management.

Keywords: youth; caregiver; drug-therapy; self-efficacy; disease-management; patient-centered care.

Effective asthma self-management by urban African American adolescents is a critical aspect of care that should be addressed with vigilance due to the persistent disparities in disease prevalence, morbidity, and mortality compared to Caucasians.^1-3 The overarching goal of asthma self-management is to achieve symptom control, maintain normal activity levels, and minimize future risk of exacerbations and medication side effects.^4,5 Best practices for asthma self-management begin with a partnership between health care providers and clients (including parent/caregiver). This relationship should help affected individuals gain asthma control based on knowledge of their disease and treatment options, confidence and skills in trigger avoidance, medication administration, and management of acute exacerbations.^4,5

Among youth aged 18 years and younger, African Americans have the highest asthma prevalence rates of all racial and ethnic groups, and between 2001 and 2009 asthma prevalence rates rose by 50% among African American youth.⁶ As of 2015, prevalence rates for asthma among African American youth were 13.4%, as compared to 7.4% for white youth.⁷ African American youth have been found to have more frequent asthma exacerbations and related school absences than white youth.⁸ Furthermore, African American youth younger than 18 years are more likely to be admitted to the hospital for asthma and are 10 times more likely to die from asthma compared to non-Hispanic white children.⁶

Urban African American adolescents with asthma are particularly vulnerable to poor asthma self-management due to the complexity of the disease in this population.³ African American youth must deal with multiple adverse environmental conditions, lack of knowledge or disbelief concerning effective disease self-management strategies, variable access and quality of care, and the psychosocial dynamics of being young while having a chronic disease.^2,3,9-11 It is important to understand and address barriers to successful asthma self-management during adolescence, as behaviors developed during this stage of life often persist into adulthood.⁹ In this article, we review the literature on barriers to asthma self-management among African American adolescents and offer suggestions on clinical strategies for improving self-management in this vulnerable population.

 

 

Methods

The initial search strategy was developed in collaboration with an experienced librarian. Keywords, MeSH terms, and potential databases were identified. Keywords included urban, African American, adolescent, asthma, self-management, and barriers. These terms were expanded based on search results and a review of abstracts that fit the intent of our review. The search was limited to U.S. studies published between 2005 and 2017. Excluded from the search were conference abstracts, doctoral dissertations, master’s theses, meta-analyses, systematic reviews, and studies conducted outside of the United States. Additional articles for the review were identified during the review process from the reference lists of the publications.

Abstracts were reviewed for articles that reported a study population inclusive of African American adolescents with asthma and that were related to self-management. Studies that used qualitative and other descriptive methods and cohort and randomized control trials were reviewed. Due to the limited number of articles found that exclusively focused on African Americans, the authors set a threshold for African American participants at 40% or greater for inclusion in this review.

Full papers were retrieved that met the inclusion criteria for a full review. Each author initially independently reviewed a selected number of papers and abstracted the study purpose, sample, study design, results, conclusions, and limitations. Subsequently, both authors reviewed in tandem and then discussed each selected manuscript to assure the appropriateness for inclusion. The subject matter was considered the priority for inclusion in the review. Study methods, sample size, and noted limitations were categorized but were not considered as a basis for exclusion. Thematic analysis was used to identify common themes across studies.

 

 

Results

We identified 23 papers that met our criteria (Table). Five common themes were found that related to barriers in disease self-management for African American adolescents: (a) knowledge and skills, (b) beliefs and attitudes, (c) personal/emotional factors, (d) caregivers, and (e) schools.

 

 

Knowledge and Skills

Adequate knowledge of the elements of asthma self-management is critical for achieving control of this condition. Asthma knowledge includes a basic understanding of the disease process and treatment strategies, an awareness of early signs and symptoms of worsening asthma, and an understanding of how to manage environmental triggers.^4,5 Sin and colleagues conducted one of the earlier studies to examine the influence of asthma knowledge on asthma self-management in African American adolescents and found a significant positive association between knowledge and asthma self-management behaviors.¹²

Adherence to an asthma medication, especially inhaled corticosteroids (ICS), is one of the cornerstones to successful self-management of asthma.^13,14 Consistent use of ICS therapy to control asthma symptoms and disease progression is often suboptimal in African American adolescents and tends to worsen as they age;¹⁵ studies have found lower adherence levels were more prominent in older African American adolescents and males.^13,16 In a recent study of adolescents with persistent asthma who were prescribed daily ICS, youth with greater ICS knowledge as assessed using a standardized instrument demonstrated significantly higher adherence rates.¹³ Proper technique in the use of an inhaler is also important in medication administration. Asthma ICS medication delivery devices vary significantly and require different techniques for medication administration. However, inhaler device skills have been found to be very inadequate in high-risk African American adolescents.¹⁷ Thus, knowledge related to ICS therapy and proper skills in the use of inhaler devices is an important aspect of asthma self-management that have been found to be inadequate in African American Adolescents.

Interventions and programs geared to improving education may lead to improved self-management. Multisystemic Therapy-Health Care (MST-HC) is a tailored home-based intervention that includes knowledge and skill-building components. In a study of African American youth with poorly controlled asthma, the program was found to improve illness management.¹⁸ In addition, adolescents who complete formal asthma education programs demonstrate significantly higher scores in self-management than those youth who do not participate in these programs.^13,19 Unfortunately, few African American teens report participation in an asthma education program.¹⁹ In a study of a motivational interviewing intervention to improve controller medication adherence for African American adolescents,¹⁴ youth reported gaining more knowledge about their asthma medications and were significantly more motivated to take their controller medications after participating in the intervention; however, while adherence to controller medications was greater than baseline, it was not significantly different.¹⁴ This study demonstrated the value of asthma education and the feasibility of a motivational intervention to support controller medication adherence. However, this study also demonstrated the complexity of medication adherence in that neither knowledge or motivation led to significant changes in medication adherence among African American adolescents.

Low health literacy can also act as a barrier to asthma self-management. Health literacy requires skills and knowledge that enable an individual to communicate, process, and understand basic health information that informs health decisions.²⁰ Health literacy was found to be associated with indicators of poor disease self-management among urban African American adolescents in grades 9 through 12.²¹ In this study, health literacy was established using questions about confidence in filling out medical forms, self-reported problems with learning about the youth’s medical condition, and the need for assistance in reading hospital materials. Adolescents with poor health literacy scores were more likely to reside in a household with the following characteristics: mother with less than a high school education, Medicaid health insurance, family members with a body mass index exceeding the 85th percentile, and lack of rescue medication. Poor health literacy was most common among younger adolescents (ie, ninth graders). Some youth with poor health literacy also reported more emergency department visits, hospitalizations, and lower overall quality of life.²¹

Beliefs and Attitudes

Beliefs and attitudes towards taking asthma medications can act as barriers to adherence in the adolescent. African American adolescents often report the belief that ICS are not helpful or necessary.^16,22-25 These beliefs have been correlated with a lack of understanding of the inflammatory mechanisms of asthma, reports of asthma attacks despite use of controller medications, fear of addiction to medications, and a belief that nontraditional interventions (eg, exercise) will work better to get rid of asthma or abate symptoms.^16-19,22-24 African American adolescents also report beliefs that asthma will go away or get better as they age, and they are willing to forgo the use of controller medications based on these beliefs.²⁴

African American adolescents often engage in asthma self-management independent of caregivers. These youth describe asthma self-management activities an annoyance and of low priority in part due to competing tasks and negative interactions with caregivers.²⁵ During early adolescence asthma self-management is often suboptimal, and as youth age they become less observant regarding their asthma and are less likely to seek help.²⁶ Adolescents’ beliefs and low prioritization of asthma self-management may contribute to forgetfulness and loss of inhalers, which are common reasons reported for poor adherence to ICS.^16,23-26 Further, the role of caregivers during this period has often been overlooked. Caregivers of African American adolescents have been found to be stressed and overwhelmed with personal responsibilities and neighborhood conditions, leaving them little time to attend to the asthma self-management behavior of youth. Due to these contextual factors, interactions with chronically ill youth may be strained, resulting in negative interactions with youth related to asthma self-management. However, in an intervention study that used multisystemic therapy (an approach that targets the affected individual, family, and community), improvement in positive parenting behaviors related to asthma self-management contributed to improved ICS adherence by adolescents.²⁷

Adolescents can perceive traditional asthma self-management as conflicting with their own personal and/or cultural beliefs. They may seek options beyond the use of medicine and have voiced preferences for behaviors that they believe will “strengthen their lungs” more naturally.²⁴ An appreciation of how youth might use complementary/alternative medicine (CAM) as an adjunctive therapy or in place of evidence-based asthma care is important to understanding the potential effect on morbidity and mortality. Behaviors and beliefs about the use of CAM have not been well studied among urban African American adolescents with asthma. Only one study was found that assessed the use of CAM among a primarily urban African American adolescent population. In that study, 71% of the population reported using some form of CAM during the past 30 days.²⁸ Prayer and relaxation were the most frequently used strategies in the management of asthma symptoms. Perceived efficacy of relaxation and prayer among teens who engaged in this form of CAM was 87% and 85%, respectively. Other CAM strategies included yoga, meditation, guided imagery, and biofeedback. When adolescents were asked if they shared their use of CAM in asthma management with a health care provider, most reported sharing the use of yoga and dietary changes but were least likely to share their use of prayer and guided imagery.²⁸

Personal/Emotional Factors

African American adolescents have reported asthma as a limiting factor in terms of both physical and social activities. They perceive asthma as a burden to themselves and others (eg, peers, family, coaches).^9,25 The burden of asthma is further exemplified in the emotional response to the symptoms of the disease and the self-management responsibilities. The need to prevent and respond to asthma symptoms is associated with being embarrassed, frustrated, angry, annoyed, worried, lonely, and isolated.^9,11,25 Negative coping strategies by youth in response to psychosocial experiences include decisions to disregard or give minimal attention to asthma symptoms and to delay or not take prescribed medications. Students report ignoring asthma symptom management while engaging in physical activities to maintain a sense of normalcy among peers and as a way of dealing with perceptions by coaches or teachers that they are weak or in need of being protected.^24,25

Negative thoughts and experiences can result in depressive disorders and poor quality of life. Depression is a common finding among urban youth with asthma.^29,30 Youth diagnosed with asthma who have comorbid depression may benefit from interventions to improve self-management. In a secondary analysis from a Web-based asthma management intervention targeting African American adolescents, depression was found to have a modifying effect on the emotional domain of quality of life for youth in the intervention arm of the study. This finding indicates that participants who were depressed and who reported low levels of emotional quality of life benefited from the Web-based interventions that targeted self-management.³¹

Caregivers

Caregivers (especially moms) are a common source of support for the development and implementation of asthma self-management behaviors in adolescents.³² Caregivers sometimes hold beliefs similar to those of youth and believe the urban environment can act as a barrier to asthma management.^9,25,32 They describe the complexity of asthma treatment plans, a lack of understanding of the disease process, and insensitivity of health care providers to their expressed needs along with the providers’ limited cultural awareness in the development of self-management plans.^9,22,33 Caregivers describe how family finances, insurance gaps, access to care, and their own familial/cultural beliefs influence their decisions and ability to support their child’s asthma management.³³ When faced with the cost of care they report instances of having to decide between necessities such as food and housing or co-pays for medications and office visits.^22,33 They also report concerns about visits with multiple providers due to an inability to access their primary care provider, which can lead to delays in their child being diagnosed with asthma.²²

Caregivers report a need to include culturally based practices, past experiences, and personal beliefs into the adolescents’ asthma management plan.^22,32,33 In a small interview-based study of caregivers residing in 3 New Jersey public housing communities, caregivers reported preferring “familial” methods of controlling asthma (eg, restriction of activities; use of showers, steam, vaporizers, and nebulizers) over evidence-based recommendations. Many caregivers were confused or lacked knowledge about asthma action plans.³³ Caregivers have also been found to lack adequate or accurate knowledge related to asthma medications and factors that improved or worsened asthma. While caregivers report a desire to help educate their teens by passing on what they know, their lack of adequate asthma knowledge may hamper their efforts and potentially worsen the teens’ asthma self-management.³²

While African American caregivers often describe themselves as hypervigilant concerning their child’s asthma, they may report different information than their adolescent when both are questioned about asthma symptom experiences and functional status.³⁴ Factors increasing the level of congruence between caregiver and teen asthma symptom reports were found to be related to the adolescents’ age and asthma disease classification. Symptom questionnaire responses of older teens and those with mild intermittent asthma were more likely to be similar to caregiver reports. The researchers concluded that clinicians and researchers may obtain reliable asthma symptom and functional status reports by asking the adolescent directly.³⁴

Schools

Caregivers and adolescents describe schools as a threat to self-management and the overall health of youth with asthma.^9,32 They perceive that a lack of knowledge by staff, teachers, and coaches contributes to inattentiveness or disbelief in the credibility of reported asthma symptoms by youth.^11,23 These misperceptions and the lack of attentiveness by adults in the school may pose safety and health issues for African American youth.^9,25,33,34 For example, adolescents report pressure from teacher, coaches, and peers in school settings to partake in sports and/or gym classes. Youth want to identify with healthy peers and thus often choose not to take asthma medications during such activities or opt to continue participating while being compromised by airway obstruction. Of great concern were reports by caregivers and teens of not being allowed to call a parent for support or retrieve their medications when needed for asthma symptoms.³²

Future Research and Practice Implications

In this review, we identified 5 common themes around barriers to asthma self-management for African American adolescents (knowledge and skills, beliefs and attitudes, personal/emotional factors, caregivers, and schools). Caregivers, especially mothers, play a pivotal role in the development of effective asthma self-management behaviors. Depsite good intentions, there is evidence of caregivers passing on ineffective experiential and culturally based beliefs and practices to their adolescents that can negatively influence self-care behaviors.^13,28,38 Studies are needed to further investigate these findings among caregivers as their beliefs and practices for asthma self-management have been found to coexist among adolescents. Studies that investigate how to incorporate caregiver asthma knowledge, cultural beliefs and behaviors in developing self-management interventions have the potential to positively influence asthma outcomes among African American adolescents.²⁷ The unique cultural beliefs, contextual environmental, and social disparities faced by African American caregivers should not be neglected.

African American adolescents, like adolescents in other racial or ethnic groups, desire to be autonomous in their asthma self-management. However, as adolescents age their adherence behaviors often decline. This may suggest a need for a longer transition period to self-management that extends into emerging adulthood (18-25 years). While youth want to feel supported, there appears to be a fine line between receiving needed support and what youth describe as “nagging” behaviors by adults. Additional investigations into how asthma responsibilities are transitioned from the parent to youth and how best to support the development and maintenance of related behaviors and skills are warranted. In addition, teens described problems related to communicating with health care providers, noting a lack of clarity in explanations received about how to manage their asthma. Some teens believed the communication challenges were based on beliefs and biases held by providers that African American youth had limited capacities for self-management.⁹ There is a need to better understand interactions among African American adolescents, parents, and clinicians so that communication and transitioning asthma care to the youth will produce optimal health outcomes.

According to asthma guidelines, the patient-provider relationship is essential to effective asthma self-management.^4,5 However, there is little mention in the literature of team-based care. Clinicians such as physicians, physician assistants, and nurse practitioners provide direct care to adolescents in terms of disease management and the overall effectiveness of treatment plans. African American youth demonstrate a need for asthma education that is comprehensive and that is contextualized to their daily lives. A team-based approach to care that includes social workers and community health workers may help to extend the reach of clinicians. Follow-up times with families and youth between office visits can be used to support adolescents to develop asthma self-management and allow them a safe space to describe frustrations and other emotions that contribute to their desire to be disease-free.

Summary

Asthma is a chronic disease that is often more severe and difficult to manage in African American adolescents. While African American adolescents describe developmental needs like those of other youth, cultural beliefs and contextual experiences influence their self-care management in unique ways. Opportunities exist to better understand the needs of African American adolescents and to help them successfully gain the knowledge, skills, and behaviors needed to effectively engage in self-management of their asthma.

Corresponding author: Wanda Gibson-Scipio, PhD, FNP-BC, FAANP, 5557 Cass Ave., 346 Cohn Building, Detroit, MI 48324; gibsonsc@wayne.edu.

Financial disclosures: None.

From the Division of General Internal Medicine (Dr. Venkataramani), and the Department of Pediatrics (Dr. Venkataramani and Dr. Solomon), Johns Hopkins University School of Medicine, Baltimore, MD.

In 2003, the American Academy of Pediatrics (AAP) published the recommendations of its Task Force on the Family, an initiative borne of the recognition that pediatricians have an important role in promoting well-functioning families as a means of ultimately promoting pediatric health.¹ Among the various facets of “family pediatrics” discussed in these recommendations was the practice of addressing caregiver health or health behaviors which directly impact children’s health. “Pediatricians have both opportunity and reason to take note of the health of their young patients’ parents,” declared the Task Force.¹ Now, 15 years later, despite growing evidence to support the promotion of caregiver health as a means to improve child health, pediatric providers continue to face challenges in successfully fulfilling this aspect of family pediatrics, challenges that we believe deserve the attention of adult providers and health systems.

Benefits Beyond Pediatric Preventive Care

Drawing upon evidence showing that caregiver health or health behaviors impact children’s health (the “reason” to intervene), current guidelines identify several caregiver-related issues on which pediatric providers are encouraged to focus their caregiver health promotion efforts. Specifically, Bright Futures, the AAP’s comprehensive evidence-driven resource for guidance regarding pediatric preventive care in the United States, highlights several caregiver health-related issues to be addressed during pediatric primary care visits.² For example, in recognition of the multiple detrimental effects secondhand tobacco smoke exposure has on child health,^3-5 the AAP recommends pediatrician-led parental tobacco use screening, counseling, and support of cessation efforts (including prescription of nicotine replacement therapies), practices that are also supported by the American Medical Association.^2,3,5 Similarly, in order to promote the protection of children against pertussis and influenza, Bright Futures recommends screening and encouraging caregiver immunization against these diseases.² Pediatricians are encouraged to routinely screen for maternal depression, given the far-reaching implications of caregiver mental health on children’s health,^2,6,7 and more recently the AAP has recommended screening fathers for depression in the perinatal period as well.⁸ Screening and appropriate referral for caregivers (and thereby children) exposed to intimate partner violence is another practice highlighted by the guidelines.²

Efforts have been made to expand the framework to other issues with similar potential to impact current and future generations of children, such as caregiver family planning.^2,9,10 And there exist still other issues which may be particularly well-suited to being addressed through the caregiver health promotion framework, such as follow-up care for mothers with gestational diabetes. These mothers are at high-risk for the development of type 2 diabetes and having subsequent pregnancies affected by poor glycemic control, but traditionally have had poor follow-up rates in the postpartum period and beyond.¹¹ Their regular interactions with pediatric providers resulting from the frequent visits required for their infants presents an important, and as yet untapped, opportunity to re-engage them in recommended medical care and prevent adverse outcomes for their future children as well as themselves.

The maternal gestational diabetes example highlights an important point: caregiver health promotion in pediatric settings can have direct health benefits for caregivers. As such, there are arguably additional reasons for health systems and adult providers to support the practice of caregiver health promotion in pediatric settings. First, it may represent one of the only exposures to the health care setting and health promotion activities for certain caregivers. Caregivers are often younger adults, an age-group that is less likely to have a usual source of care or access preventive services, and low-income caregivers of any age are more likely to have limited health care access. Given the frequency of routine care (12 health maintenance visits in the child’s first 3 years of life),² caregivers are likely to have more consistent access with the pediatric health care system than with the adult health care system. Therefore, pediatric visits represent an important touchpoint for these adults that could be leveraged to deliver services and further engage them with the adult health care system. Improving the reach of these services is particularly important in the era of population health where health systems, and particularly accountable care organizations, assume responsibility for the health-related outcomes of communities at large.

Second, studies exploring caregiver perspectives on pediatricians addressing their depression or tobacco use suggest that caregivers appreciate and welcome pediatrician engagement in their care.^12,13 Thus, supporting these efforts enables patient-centered care delivery. And third, caregivers may be more motivated to address their own health issues or behaviors (such as substance use) when counseled on the implications of their actions on their children’s health. To the extent such counseling is more routinely (and effectively) delivered in the pediatric setting, supporting pediatrics-based counseling efforts is also in the best interest of adult health care providers.

Challenges to Caregiver Health Promotion in Pediatric Settings

Studies suggest that a fairly broad scope of caregiver health promotion activities do occur in pediatric practice. In our survey of a nationally representative sample of children’s primary care physicians (including pediatricians, family medicine physicians, and medicine-pediatrics physicians), over three-quarters of respondents reported addressing at least 3 caregiver health issues (including maternal depression, tobacco use, family planning, influenza immunization status, intimate partner violence exposure, and caregiver health insurance status) during well-infant or well-child visits.¹⁴ At the same time, we found limited depth in practice in terms of the regularity with which caregiver issues are addressed at visits or, when applicable, services beyond screening are offered to caregivers. For example, we found that only 36% of physicians addressed caregiver exposure to intimate partner violence in at least half of the well-infant or well-child visits they conducted.¹⁴ And while the vast majority of our respondents addressed parental tobacco use with some regularity, less than 15% reported assisting parents with cessation efforts by prescribing cessation therapies. Other studies exploring practices surrounding maternal depression, intimate partner violence screening, or tobacco cessation counseling have revealed similar patterns with regards to the reach of caregiver health promotion in practices across the country.^15-18

Such variability in practice seems to stem primarily from structural and/or organizational barriers to caregiver health promotion in pediatric primary care settings, such as limited time, inability to bill for services provided to caregivers, and lack of efficient systems to refer caregivers to adult providers or services. These structural barriers could lead to attitudinal barriers (ie, pediatric physicians’ reluctance to address caregiver health). Attitudinal or physician-associated barriers may arise in instances when the caregiver health issue’s relevance to child health is less clear or expected actions are perceived as being beyond the scope of pediatric practice, raising concerns about personal effectiveness and liability. But it appears that when caregiver health issues clearly impact child health, and the role of the pediatrician is to screen and counsel in the context of pediatric implications of caregiver health or health behaviors, the majority of pediatric providers do endorse a sense of personal responsibility to address these issues. In our survey, for example, the vast majority of pediatric primary care physicians endorsed maternal depression and caregiver tobacco use as relevant to child well-being, and also endorsed a sense of personal responsibility to address these issues.¹⁹

Structural or organizational barriers thus appear to play a larger role overall in influencing caregiver health promotion practices. Various studies have characterized these barriers as they relate to caregiver health promotion, and lack of time is a paramount concern.^14,20 This is not surprising, given the multiple competing interests for a pediatrician’s time during already time-constrained well-child visits (which include growth and development assessment, anticipatory guidance provision, delivery of children’s preventive care services, and addressing any acute concerns). The time constraints may be even more acutely felt if the results of screening necessitate additional action, such as referral to relevant services. We found that a lack of referral resources or complex referral mechanisms were cited by over half of children’s primary care physicians as general barriers to caregiver health promotion, and in particular by pediatricians (versus medicine-pediatrics or family medicine physicians).¹⁴

This highlights the key difference between family medicine and caregiver health promotion in pediatrics: the latter involves addressing adult health issues in a setting where care for adults is often not provided. While some practices that see children may provide care to adults (such as family medicine or medicine-pediatrics clinics) or are co-located with adult health care providers, most pediatric practices are not integrated with adult health care settings. As a result, the “next steps” in caregiver health promotion can prove challenging to pursue, thereby limiting the beneficial impact of these activities on both child and adult health. For example, in the absence of such integration, pediatricians may find it challenging to connect mothers with positive depression screens to appropriate mental health care or parents who smoke to tobacco cessation services. In addition to leading to missed opportunities to comprehensively address caregiver health issues, such obstacles may also discourage pediatric providers from pursuing caregiver health promotion activities to begin with.

The Way Forward

How can health systems and adult health care providers support the caregiver promotion activities of pediatric primary care providers? There are several ways to enhance integration with adult practices and adult health care services. The co-location and integration of relevant caregiver-related auxiliary services at pediatric clinics is one way. In fact, when asked to identify facilitators to caregiver health promotion, pediatricians who responded to our survey most frequently endorsed the co-location of relevant providers, such as mental health professionals or social workers, as facilitators for addressing caregiver depression or intimate partner violence.¹⁴ For example, at the Harriet Lane Clinic at Johns Hopkins, the integration of a comprehensive maternal mental health team (including a part-time licensed therapist, part-time psychiatrist from an affiliated psychiatric practice, and full-time maternal case manager) has proven to be an effective, patient-oriented approach to providing services for mothers with depression.²¹ The role of health systems and adult health care providers/practices in advancing such models of care delivery is two-fold: to provide necessary staff and financial support. The latter is particularly important as many of the relevant caregiver-related services (eg, social work or case manager visits) may not generate the revenue required to support their sustained presence at pediatric sites.

Pediatric practices would also benefit from enhanced mechanisms for referral to appropriate services that are not co-located, such as tobacco cessation “quitlines.” Adopting protocolized interventions that focus on connecting parents with existing resources for their own health, such as the CEASE intervention developed for parental tobacco control in pediatrics,^22,23 is one way to streamline the referral process for pediatric practices. Another is by advancing a truly integrated electronic medical record (EMR), which enables caregiver health screenings and referral to additional services to be completed during pediatric encounters.

Finally, while only a relative minority of physicians we surveyed suggested that a lack of reimbursement for their activities served as a general barrier to caregiver health promotion, ensuring that pediatric providers are adequately compensated for their efforts on behalf of parents and guardians would undoubtedly help support their activities. Integrated EMRs could be one way to support this, particularly for services that are traditionally billed for (eg, depression screening or tobacco cessation counseling). Novel ways to reimburse pediatric providers for their contribution to adult health indicators could also be considered; for example, to the extent caregiver health promotion activities contribute to adult quality indicators (eg, postpartum depression screening rates and completion of postpartum visits) that are associated with financial rewards, health systems could consider sharing these “bonuses” among pediatric providers.

From Family Pediatrics to Family-Oriented Care

While caregiver health promotion has long been considered part of the practice of “family pediatrics,” it should more accurately be seen as an integral component of the delivery of family-oriented primary care, as it represents a novel opportunity to advance the health of not only children, but also their caregivers. Following existing preventive care guidelines, pediatricians currently engage in a variety of activities to promote child and caregiver health, but require support to more consistently and effectively address issues such as caregiver tobacco use or maternal depression. The barriers faced by pediatricians could be most effectively addressed with the engagement of adult health care providers and health systems; this includes the development of an integrated EMR that would support screening activities and referral to connect caregivers with necessary follow-up resources. Further characterizing the barriers faced in pediatric settings, and exploring how health systems could provide the necessary support to address these barriers, is crucial to realizing the potential of caregiver health promotion to have multi-generational impacts on well-being.

Corresponding author: Maya Venkataramani, MD, MPH, 2024 E. Monument St., Suite 2-502, Baltimore, MD 21287; mvenkat2@jhmi.edu.

Financial disclosures: None.

From the Division of General Internal Medicine (Dr. Venkataramani), and the Department of Pediatrics (Dr. Venkataramani and Dr. Solomon), Johns Hopkins University School of Medicine, Baltimore, MD.

In 2003, the American Academy of Pediatrics (AAP) published the recommendations of its Task Force on the Family, an initiative borne of the recognition that pediatricians have an important role in promoting well-functioning families as a means of ultimately promoting pediatric health.¹ Among the various facets of “family pediatrics” discussed in these recommendations was the practice of addressing caregiver health or health behaviors which directly impact children’s health. “Pediatricians have both opportunity and reason to take note of the health of their young patients’ parents,” declared the Task Force.¹ Now, 15 years later, despite growing evidence to support the promotion of caregiver health as a means to improve child health, pediatric providers continue to face challenges in successfully fulfilling this aspect of family pediatrics, challenges that we believe deserve the attention of adult providers and health systems.

Benefits Beyond Pediatric Preventive Care

Drawing upon evidence showing that caregiver health or health behaviors impact children’s health (the “reason” to intervene), current guidelines identify several caregiver-related issues on which pediatric providers are encouraged to focus their caregiver health promotion efforts. Specifically, Bright Futures, the AAP’s comprehensive evidence-driven resource for guidance regarding pediatric preventive care in the United States, highlights several caregiver health-related issues to be addressed during pediatric primary care visits.² For example, in recognition of the multiple detrimental effects secondhand tobacco smoke exposure has on child health,^3-5 the AAP recommends pediatrician-led parental tobacco use screening, counseling, and support of cessation efforts (including prescription of nicotine replacement therapies), practices that are also supported by the American Medical Association.^2,3,5 Similarly, in order to promote the protection of children against pertussis and influenza, Bright Futures recommends screening and encouraging caregiver immunization against these diseases.² Pediatricians are encouraged to routinely screen for maternal depression, given the far-reaching implications of caregiver mental health on children’s health,^2,6,7 and more recently the AAP has recommended screening fathers for depression in the perinatal period as well.⁸ Screening and appropriate referral for caregivers (and thereby children) exposed to intimate partner violence is another practice highlighted by the guidelines.²

Efforts have been made to expand the framework to other issues with similar potential to impact current and future generations of children, such as caregiver family planning.^2,9,10 And there exist still other issues which may be particularly well-suited to being addressed through the caregiver health promotion framework, such as follow-up care for mothers with gestational diabetes. These mothers are at high-risk for the development of type 2 diabetes and having subsequent pregnancies affected by poor glycemic control, but traditionally have had poor follow-up rates in the postpartum period and beyond.¹¹ Their regular interactions with pediatric providers resulting from the frequent visits required for their infants presents an important, and as yet untapped, opportunity to re-engage them in recommended medical care and prevent adverse outcomes for their future children as well as themselves.

The maternal gestational diabetes example highlights an important point: caregiver health promotion in pediatric settings can have direct health benefits for caregivers. As such, there are arguably additional reasons for health systems and adult providers to support the practice of caregiver health promotion in pediatric settings. First, it may represent one of the only exposures to the health care setting and health promotion activities for certain caregivers. Caregivers are often younger adults, an age-group that is less likely to have a usual source of care or access preventive services, and low-income caregivers of any age are more likely to have limited health care access. Given the frequency of routine care (12 health maintenance visits in the child’s first 3 years of life),² caregivers are likely to have more consistent access with the pediatric health care system than with the adult health care system. Therefore, pediatric visits represent an important touchpoint for these adults that could be leveraged to deliver services and further engage them with the adult health care system. Improving the reach of these services is particularly important in the era of population health where health systems, and particularly accountable care organizations, assume responsibility for the health-related outcomes of communities at large.

Second, studies exploring caregiver perspectives on pediatricians addressing their depression or tobacco use suggest that caregivers appreciate and welcome pediatrician engagement in their care.^12,13 Thus, supporting these efforts enables patient-centered care delivery. And third, caregivers may be more motivated to address their own health issues or behaviors (such as substance use) when counseled on the implications of their actions on their children’s health. To the extent such counseling is more routinely (and effectively) delivered in the pediatric setting, supporting pediatrics-based counseling efforts is also in the best interest of adult health care providers.

Challenges to Caregiver Health Promotion in Pediatric Settings

Studies suggest that a fairly broad scope of caregiver health promotion activities do occur in pediatric practice. In our survey of a nationally representative sample of children’s primary care physicians (including pediatricians, family medicine physicians, and medicine-pediatrics physicians), over three-quarters of respondents reported addressing at least 3 caregiver health issues (including maternal depression, tobacco use, family planning, influenza immunization status, intimate partner violence exposure, and caregiver health insurance status) during well-infant or well-child visits.¹⁴ At the same time, we found limited depth in practice in terms of the regularity with which caregiver issues are addressed at visits or, when applicable, services beyond screening are offered to caregivers. For example, we found that only 36% of physicians addressed caregiver exposure to intimate partner violence in at least half of the well-infant or well-child visits they conducted.¹⁴ And while the vast majority of our respondents addressed parental tobacco use with some regularity, less than 15% reported assisting parents with cessation efforts by prescribing cessation therapies. Other studies exploring practices surrounding maternal depression, intimate partner violence screening, or tobacco cessation counseling have revealed similar patterns with regards to the reach of caregiver health promotion in practices across the country.^15-18

Such variability in practice seems to stem primarily from structural and/or organizational barriers to caregiver health promotion in pediatric primary care settings, such as limited time, inability to bill for services provided to caregivers, and lack of efficient systems to refer caregivers to adult providers or services. These structural barriers could lead to attitudinal barriers (ie, pediatric physicians’ reluctance to address caregiver health). Attitudinal or physician-associated barriers may arise in instances when the caregiver health issue’s relevance to child health is less clear or expected actions are perceived as being beyond the scope of pediatric practice, raising concerns about personal effectiveness and liability. But it appears that when caregiver health issues clearly impact child health, and the role of the pediatrician is to screen and counsel in the context of pediatric implications of caregiver health or health behaviors, the majority of pediatric providers do endorse a sense of personal responsibility to address these issues. In our survey, for example, the vast majority of pediatric primary care physicians endorsed maternal depression and caregiver tobacco use as relevant to child well-being, and also endorsed a sense of personal responsibility to address these issues.¹⁹

Structural or organizational barriers thus appear to play a larger role overall in influencing caregiver health promotion practices. Various studies have characterized these barriers as they relate to caregiver health promotion, and lack of time is a paramount concern.^14,20 This is not surprising, given the multiple competing interests for a pediatrician’s time during already time-constrained well-child visits (which include growth and development assessment, anticipatory guidance provision, delivery of children’s preventive care services, and addressing any acute concerns). The time constraints may be even more acutely felt if the results of screening necessitate additional action, such as referral to relevant services. We found that a lack of referral resources or complex referral mechanisms were cited by over half of children’s primary care physicians as general barriers to caregiver health promotion, and in particular by pediatricians (versus medicine-pediatrics or family medicine physicians).¹⁴

This highlights the key difference between family medicine and caregiver health promotion in pediatrics: the latter involves addressing adult health issues in a setting where care for adults is often not provided. While some practices that see children may provide care to adults (such as family medicine or medicine-pediatrics clinics) or are co-located with adult health care providers, most pediatric practices are not integrated with adult health care settings. As a result, the “next steps” in caregiver health promotion can prove challenging to pursue, thereby limiting the beneficial impact of these activities on both child and adult health. For example, in the absence of such integration, pediatricians may find it challenging to connect mothers with positive depression screens to appropriate mental health care or parents who smoke to tobacco cessation services. In addition to leading to missed opportunities to comprehensively address caregiver health issues, such obstacles may also discourage pediatric providers from pursuing caregiver health promotion activities to begin with.

The Way Forward

How can health systems and adult health care providers support the caregiver promotion activities of pediatric primary care providers? There are several ways to enhance integration with adult practices and adult health care services. The co-location and integration of relevant caregiver-related auxiliary services at pediatric clinics is one way. In fact, when asked to identify facilitators to caregiver health promotion, pediatricians who responded to our survey most frequently endorsed the co-location of relevant providers, such as mental health professionals or social workers, as facilitators for addressing caregiver depression or intimate partner violence.¹⁴ For example, at the Harriet Lane Clinic at Johns Hopkins, the integration of a comprehensive maternal mental health team (including a part-time licensed therapist, part-time psychiatrist from an affiliated psychiatric practice, and full-time maternal case manager) has proven to be an effective, patient-oriented approach to providing services for mothers with depression.²¹ The role of health systems and adult health care providers/practices in advancing such models of care delivery is two-fold: to provide necessary staff and financial support. The latter is particularly important as many of the relevant caregiver-related services (eg, social work or case manager visits) may not generate the revenue required to support their sustained presence at pediatric sites.

Pediatric practices would also benefit from enhanced mechanisms for referral to appropriate services that are not co-located, such as tobacco cessation “quitlines.” Adopting protocolized interventions that focus on connecting parents with existing resources for their own health, such as the CEASE intervention developed for parental tobacco control in pediatrics,^22,23 is one way to streamline the referral process for pediatric practices. Another is by advancing a truly integrated electronic medical record (EMR), which enables caregiver health screenings and referral to additional services to be completed during pediatric encounters.

Finally, while only a relative minority of physicians we surveyed suggested that a lack of reimbursement for their activities served as a general barrier to caregiver health promotion, ensuring that pediatric providers are adequately compensated for their efforts on behalf of parents and guardians would undoubtedly help support their activities. Integrated EMRs could be one way to support this, particularly for services that are traditionally billed for (eg, depression screening or tobacco cessation counseling). Novel ways to reimburse pediatric providers for their contribution to adult health indicators could also be considered; for example, to the extent caregiver health promotion activities contribute to adult quality indicators (eg, postpartum depression screening rates and completion of postpartum visits) that are associated with financial rewards, health systems could consider sharing these “bonuses” among pediatric providers.

From Family Pediatrics to Family-Oriented Care

While caregiver health promotion has long been considered part of the practice of “family pediatrics,” it should more accurately be seen as an integral component of the delivery of family-oriented primary care, as it represents a novel opportunity to advance the health of not only children, but also their caregivers. Following existing preventive care guidelines, pediatricians currently engage in a variety of activities to promote child and caregiver health, but require support to more consistently and effectively address issues such as caregiver tobacco use or maternal depression. The barriers faced by pediatricians could be most effectively addressed with the engagement of adult health care providers and health systems; this includes the development of an integrated EMR that would support screening activities and referral to connect caregivers with necessary follow-up resources. Further characterizing the barriers faced in pediatric settings, and exploring how health systems could provide the necessary support to address these barriers, is crucial to realizing the potential of caregiver health promotion to have multi-generational impacts on well-being.

Corresponding author: Maya Venkataramani, MD, MPH, 2024 E. Monument St., Suite 2-502, Baltimore, MD 21287; mvenkat2@jhmi.edu.

Financial disclosures: None.

From the Division of General Internal Medicine (Dr. Venkataramani), and the Department of Pediatrics (Dr. Venkataramani and Dr. Solomon), Johns Hopkins University School of Medicine, Baltimore, MD.

In 2003, the American Academy of Pediatrics (AAP) published the recommendations of its Task Force on the Family, an initiative borne of the recognition that pediatricians have an important role in promoting well-functioning families as a means of ultimately promoting pediatric health.¹ Among the various facets of “family pediatrics” discussed in these recommendations was the practice of addressing caregiver health or health behaviors which directly impact children’s health. “Pediatricians have both opportunity and reason to take note of the health of their young patients’ parents,” declared the Task Force.¹ Now, 15 years later, despite growing evidence to support the promotion of caregiver health as a means to improve child health, pediatric providers continue to face challenges in successfully fulfilling this aspect of family pediatrics, challenges that we believe deserve the attention of adult providers and health systems.

Benefits Beyond Pediatric Preventive Care

Drawing upon evidence showing that caregiver health or health behaviors impact children’s health (the “reason” to intervene), current guidelines identify several caregiver-related issues on which pediatric providers are encouraged to focus their caregiver health promotion efforts. Specifically, Bright Futures, the AAP’s comprehensive evidence-driven resource for guidance regarding pediatric preventive care in the United States, highlights several caregiver health-related issues to be addressed during pediatric primary care visits.² For example, in recognition of the multiple detrimental effects secondhand tobacco smoke exposure has on child health,^3-5 the AAP recommends pediatrician-led parental tobacco use screening, counseling, and support of cessation efforts (including prescription of nicotine replacement therapies), practices that are also supported by the American Medical Association.^2,3,5 Similarly, in order to promote the protection of children against pertussis and influenza, Bright Futures recommends screening and encouraging caregiver immunization against these diseases.² Pediatricians are encouraged to routinely screen for maternal depression, given the far-reaching implications of caregiver mental health on children’s health,^2,6,7 and more recently the AAP has recommended screening fathers for depression in the perinatal period as well.⁸ Screening and appropriate referral for caregivers (and thereby children) exposed to intimate partner violence is another practice highlighted by the guidelines.²

Efforts have been made to expand the framework to other issues with similar potential to impact current and future generations of children, such as caregiver family planning.^2,9,10 And there exist still other issues which may be particularly well-suited to being addressed through the caregiver health promotion framework, such as follow-up care for mothers with gestational diabetes. These mothers are at high-risk for the development of type 2 diabetes and having subsequent pregnancies affected by poor glycemic control, but traditionally have had poor follow-up rates in the postpartum period and beyond.¹¹ Their regular interactions with pediatric providers resulting from the frequent visits required for their infants presents an important, and as yet untapped, opportunity to re-engage them in recommended medical care and prevent adverse outcomes for their future children as well as themselves.

The maternal gestational diabetes example highlights an important point: caregiver health promotion in pediatric settings can have direct health benefits for caregivers. As such, there are arguably additional reasons for health systems and adult providers to support the practice of caregiver health promotion in pediatric settings. First, it may represent one of the only exposures to the health care setting and health promotion activities for certain caregivers. Caregivers are often younger adults, an age-group that is less likely to have a usual source of care or access preventive services, and low-income caregivers of any age are more likely to have limited health care access. Given the frequency of routine care (12 health maintenance visits in the child’s first 3 years of life),² caregivers are likely to have more consistent access with the pediatric health care system than with the adult health care system. Therefore, pediatric visits represent an important touchpoint for these adults that could be leveraged to deliver services and further engage them with the adult health care system. Improving the reach of these services is particularly important in the era of population health where health systems, and particularly accountable care organizations, assume responsibility for the health-related outcomes of communities at large.

Second, studies exploring caregiver perspectives on pediatricians addressing their depression or tobacco use suggest that caregivers appreciate and welcome pediatrician engagement in their care.^12,13 Thus, supporting these efforts enables patient-centered care delivery. And third, caregivers may be more motivated to address their own health issues or behaviors (such as substance use) when counseled on the implications of their actions on their children’s health. To the extent such counseling is more routinely (and effectively) delivered in the pediatric setting, supporting pediatrics-based counseling efforts is also in the best interest of adult health care providers.

Challenges to Caregiver Health Promotion in Pediatric Settings

Studies suggest that a fairly broad scope of caregiver health promotion activities do occur in pediatric practice. In our survey of a nationally representative sample of children’s primary care physicians (including pediatricians, family medicine physicians, and medicine-pediatrics physicians), over three-quarters of respondents reported addressing at least 3 caregiver health issues (including maternal depression, tobacco use, family planning, influenza immunization status, intimate partner violence exposure, and caregiver health insurance status) during well-infant or well-child visits.¹⁴ At the same time, we found limited depth in practice in terms of the regularity with which caregiver issues are addressed at visits or, when applicable, services beyond screening are offered to caregivers. For example, we found that only 36% of physicians addressed caregiver exposure to intimate partner violence in at least half of the well-infant or well-child visits they conducted.¹⁴ And while the vast majority of our respondents addressed parental tobacco use with some regularity, less than 15% reported assisting parents with cessation efforts by prescribing cessation therapies. Other studies exploring practices surrounding maternal depression, intimate partner violence screening, or tobacco cessation counseling have revealed similar patterns with regards to the reach of caregiver health promotion in practices across the country.^15-18

Such variability in practice seems to stem primarily from structural and/or organizational barriers to caregiver health promotion in pediatric primary care settings, such as limited time, inability to bill for services provided to caregivers, and lack of efficient systems to refer caregivers to adult providers or services. These structural barriers could lead to attitudinal barriers (ie, pediatric physicians’ reluctance to address caregiver health). Attitudinal or physician-associated barriers may arise in instances when the caregiver health issue’s relevance to child health is less clear or expected actions are perceived as being beyond the scope of pediatric practice, raising concerns about personal effectiveness and liability. But it appears that when caregiver health issues clearly impact child health, and the role of the pediatrician is to screen and counsel in the context of pediatric implications of caregiver health or health behaviors, the majority of pediatric providers do endorse a sense of personal responsibility to address these issues. In our survey, for example, the vast majority of pediatric primary care physicians endorsed maternal depression and caregiver tobacco use as relevant to child well-being, and also endorsed a sense of personal responsibility to address these issues.¹⁹

Structural or organizational barriers thus appear to play a larger role overall in influencing caregiver health promotion practices. Various studies have characterized these barriers as they relate to caregiver health promotion, and lack of time is a paramount concern.^14,20 This is not surprising, given the multiple competing interests for a pediatrician’s time during already time-constrained well-child visits (which include growth and development assessment, anticipatory guidance provision, delivery of children’s preventive care services, and addressing any acute concerns). The time constraints may be even more acutely felt if the results of screening necessitate additional action, such as referral to relevant services. We found that a lack of referral resources or complex referral mechanisms were cited by over half of children’s primary care physicians as general barriers to caregiver health promotion, and in particular by pediatricians (versus medicine-pediatrics or family medicine physicians).¹⁴

This highlights the key difference between family medicine and caregiver health promotion in pediatrics: the latter involves addressing adult health issues in a setting where care for adults is often not provided. While some practices that see children may provide care to adults (such as family medicine or medicine-pediatrics clinics) or are co-located with adult health care providers, most pediatric practices are not integrated with adult health care settings. As a result, the “next steps” in caregiver health promotion can prove challenging to pursue, thereby limiting the beneficial impact of these activities on both child and adult health. For example, in the absence of such integration, pediatricians may find it challenging to connect mothers with positive depression screens to appropriate mental health care or parents who smoke to tobacco cessation services. In addition to leading to missed opportunities to comprehensively address caregiver health issues, such obstacles may also discourage pediatric providers from pursuing caregiver health promotion activities to begin with.

The Way Forward

How can health systems and adult health care providers support the caregiver promotion activities of pediatric primary care providers? There are several ways to enhance integration with adult practices and adult health care services. The co-location and integration of relevant caregiver-related auxiliary services at pediatric clinics is one way. In fact, when asked to identify facilitators to caregiver health promotion, pediatricians who responded to our survey most frequently endorsed the co-location of relevant providers, such as mental health professionals or social workers, as facilitators for addressing caregiver depression or intimate partner violence.¹⁴ For example, at the Harriet Lane Clinic at Johns Hopkins, the integration of a comprehensive maternal mental health team (including a part-time licensed therapist, part-time psychiatrist from an affiliated psychiatric practice, and full-time maternal case manager) has proven to be an effective, patient-oriented approach to providing services for mothers with depression.²¹ The role of health systems and adult health care providers/practices in advancing such models of care delivery is two-fold: to provide necessary staff and financial support. The latter is particularly important as many of the relevant caregiver-related services (eg, social work or case manager visits) may not generate the revenue required to support their sustained presence at pediatric sites.

Pediatric practices would also benefit from enhanced mechanisms for referral to appropriate services that are not co-located, such as tobacco cessation “quitlines.” Adopting protocolized interventions that focus on connecting parents with existing resources for their own health, such as the CEASE intervention developed for parental tobacco control in pediatrics,^22,23 is one way to streamline the referral process for pediatric practices. Another is by advancing a truly integrated electronic medical record (EMR), which enables caregiver health screenings and referral to additional services to be completed during pediatric encounters.

Finally, while only a relative minority of physicians we surveyed suggested that a lack of reimbursement for their activities served as a general barrier to caregiver health promotion, ensuring that pediatric providers are adequately compensated for their efforts on behalf of parents and guardians would undoubtedly help support their activities. Integrated EMRs could be one way to support this, particularly for services that are traditionally billed for (eg, depression screening or tobacco cessation counseling). Novel ways to reimburse pediatric providers for their contribution to adult health indicators could also be considered; for example, to the extent caregiver health promotion activities contribute to adult quality indicators (eg, postpartum depression screening rates and completion of postpartum visits) that are associated with financial rewards, health systems could consider sharing these “bonuses” among pediatric providers.

From Family Pediatrics to Family-Oriented Care

While caregiver health promotion has long been considered part of the practice of “family pediatrics,” it should more accurately be seen as an integral component of the delivery of family-oriented primary care, as it represents a novel opportunity to advance the health of not only children, but also their caregivers. Following existing preventive care guidelines, pediatricians currently engage in a variety of activities to promote child and caregiver health, but require support to more consistently and effectively address issues such as caregiver tobacco use or maternal depression. The barriers faced by pediatricians could be most effectively addressed with the engagement of adult health care providers and health systems; this includes the development of an integrated EMR that would support screening activities and referral to connect caregivers with necessary follow-up resources. Further characterizing the barriers faced in pediatric settings, and exploring how health systems could provide the necessary support to address these barriers, is crucial to realizing the potential of caregiver health promotion to have multi-generational impacts on well-being.

Corresponding author: Maya Venkataramani, MD, MPH, 2024 E. Monument St., Suite 2-502, Baltimore, MD 21287; mvenkat2@jhmi.edu.

Financial disclosures: None.

I recently saw Anaeli (not her real name), an 8-year-old Mexican American girl, in clinic for worsening constipation. Her mother brought her in because of a year’s worth of increasingly irregular bowel movements. Looking through her chart, it was easy to find the starting point of Anaeli’s constipation – it aligned with her father’s deportation. U.S. Immigration and Customs Enforcement had arrested him while he was dropping Anaeli off at school.

Family separation at the border has reignited awareness of the effects of adverse childhood events. As a young pediatrician training in San Diego, I see both the impact of immigration policies on children and the resulting need for trauma-informed care. We need coordinated efforts in homes, schools, and hospitals to effectively treat affected kids.

For the past year, Anaeli’s caregivers have struggled to do so. She has been acting out, frequently crying and throwing fits about going to school. Anaeli has missed about 30 days of school because of behavioral issues.

What does 30 fewer days of first grade look like? Anaeli’s language skills are at a standstill. She cannot follow complex directions like her peers. Because of her academic shortcomings, Anaeli earned an individualized education plan and a teacher’s aide to help her focus. This aide has adopted a “tough love” attitude. Anaeli’s mom reports that she is often disciplined by long time-outs in the classroom bathroom and worries that this discipline is causing Anaeli to withhold stool to a point of loosing control and soiling herself. Since working with the aide, Anaeli has been having daily “accidents,” stooling in her pants, despite being toilet trained for years.

After the appointment, I called the school three times and was finally able to get in touch with Anaeli’s aide. She expressed frustration over Anaeli’s “lack of trying” and “meltdown” reaction to discipline. She said Anaeli’s mom was not enforcing limits at home. She told me she had successfully used time-outs in the bathroom with her own children. When I reviewed the impact of childhood trauma and more appropriate approaches to discipline, the aide grew defensive and challenged me by asking if I have kids of my own.

While I disagreed with the aide’s methods, I understood her frustration. Anaeli is not easy to help. But she is just one of a generation of children affected by the deportation of a family member. Like them, Anaeli’s health is deeply affected by stress in a way that she many not be able to verbalize.

Trauma-informed care should be an essential lens for caregivers of children who have been separated from their family. Resolving Anaeli’s constipation will require a concerted effort by her mom, health providers, teachers, and aides to encourage good behavior, use measured disciplinary tactics, and consume a high-fiber diet. In doing so, we can provide children like her with the appropriate environment to build resilience.

Dr. Parekh is a pediatrician in San Diego. Email her at pdnews@mdedge.com.

I recently saw Anaeli (not her real name), an 8-year-old Mexican American girl, in clinic for worsening constipation. Her mother brought her in because of a year’s worth of increasingly irregular bowel movements. Looking through her chart, it was easy to find the starting point of Anaeli’s constipation – it aligned with her father’s deportation. U.S. Immigration and Customs Enforcement had arrested him while he was dropping Anaeli off at school.

Family separation at the border has reignited awareness of the effects of adverse childhood events. As a young pediatrician training in San Diego, I see both the impact of immigration policies on children and the resulting need for trauma-informed care. We need coordinated efforts in homes, schools, and hospitals to effectively treat affected kids.

For the past year, Anaeli’s caregivers have struggled to do so. She has been acting out, frequently crying and throwing fits about going to school. Anaeli has missed about 30 days of school because of behavioral issues.

What does 30 fewer days of first grade look like? Anaeli’s language skills are at a standstill. She cannot follow complex directions like her peers. Because of her academic shortcomings, Anaeli earned an individualized education plan and a teacher’s aide to help her focus. This aide has adopted a “tough love” attitude. Anaeli’s mom reports that she is often disciplined by long time-outs in the classroom bathroom and worries that this discipline is causing Anaeli to withhold stool to a point of loosing control and soiling herself. Since working with the aide, Anaeli has been having daily “accidents,” stooling in her pants, despite being toilet trained for years.

After the appointment, I called the school three times and was finally able to get in touch with Anaeli’s aide. She expressed frustration over Anaeli’s “lack of trying” and “meltdown” reaction to discipline. She said Anaeli’s mom was not enforcing limits at home. She told me she had successfully used time-outs in the bathroom with her own children. When I reviewed the impact of childhood trauma and more appropriate approaches to discipline, the aide grew defensive and challenged me by asking if I have kids of my own.

While I disagreed with the aide’s methods, I understood her frustration. Anaeli is not easy to help. But she is just one of a generation of children affected by the deportation of a family member. Like them, Anaeli’s health is deeply affected by stress in a way that she many not be able to verbalize.

Trauma-informed care should be an essential lens for caregivers of children who have been separated from their family. Resolving Anaeli’s constipation will require a concerted effort by her mom, health providers, teachers, and aides to encourage good behavior, use measured disciplinary tactics, and consume a high-fiber diet. In doing so, we can provide children like her with the appropriate environment to build resilience.

Dr. Parekh is a pediatrician in San Diego. Email her at pdnews@mdedge.com.

I recently saw Anaeli (not her real name), an 8-year-old Mexican American girl, in clinic for worsening constipation. Her mother brought her in because of a year’s worth of increasingly irregular bowel movements. Looking through her chart, it was easy to find the starting point of Anaeli’s constipation – it aligned with her father’s deportation. U.S. Immigration and Customs Enforcement had arrested him while he was dropping Anaeli off at school.

Family separation at the border has reignited awareness of the effects of adverse childhood events. As a young pediatrician training in San Diego, I see both the impact of immigration policies on children and the resulting need for trauma-informed care. We need coordinated efforts in homes, schools, and hospitals to effectively treat affected kids.

For the past year, Anaeli’s caregivers have struggled to do so. She has been acting out, frequently crying and throwing fits about going to school. Anaeli has missed about 30 days of school because of behavioral issues.

What does 30 fewer days of first grade look like? Anaeli’s language skills are at a standstill. She cannot follow complex directions like her peers. Because of her academic shortcomings, Anaeli earned an individualized education plan and a teacher’s aide to help her focus. This aide has adopted a “tough love” attitude. Anaeli’s mom reports that she is often disciplined by long time-outs in the classroom bathroom and worries that this discipline is causing Anaeli to withhold stool to a point of loosing control and soiling herself. Since working with the aide, Anaeli has been having daily “accidents,” stooling in her pants, despite being toilet trained for years.

After the appointment, I called the school three times and was finally able to get in touch with Anaeli’s aide. She expressed frustration over Anaeli’s “lack of trying” and “meltdown” reaction to discipline. She said Anaeli’s mom was not enforcing limits at home. She told me she had successfully used time-outs in the bathroom with her own children. When I reviewed the impact of childhood trauma and more appropriate approaches to discipline, the aide grew defensive and challenged me by asking if I have kids of my own.

While I disagreed with the aide’s methods, I understood her frustration. Anaeli is not easy to help. But she is just one of a generation of children affected by the deportation of a family member. Like them, Anaeli’s health is deeply affected by stress in a way that she many not be able to verbalize.

Trauma-informed care should be an essential lens for caregivers of children who have been separated from their family. Resolving Anaeli’s constipation will require a concerted effort by her mom, health providers, teachers, and aides to encourage good behavior, use measured disciplinary tactics, and consume a high-fiber diet. In doing so, we can provide children like her with the appropriate environment to build resilience.

Dr. Parekh is a pediatrician in San Diego. Email her at pdnews@mdedge.com.

Survival gains among adolescents and young adults (AYAs) with cancer continue to lag behind outcomes for children and older adult patients. It’s a trend that spans decades, but clinicians and researchers are finally getting serious about trying to understand the underlying causes and are re-examining prevailing practices in an effort to address the discrepancies.

“This is a very heterogeneous group of disorders,” Rabi Hanna, MD, a pediatric hematologist and oncologist at Cleveland Clinic Children’s Hospital, Ohio, said in an interview. He’s specifically referring to the cancers that affect AYAs, who are broadly defined as patients aged 15 through 39 years. “A few cancers, such as [acute lymphoblastic leukemia], are more common in children, and others, such as breast cancer, are more common in adults. The biology may be different in the adolescent and young adult patients, which may lead to different outcomes.”

In addition, the psychosocial needs in this age group differ vastly from those in other groups. “Many of these patients are in college or have just started their families, so we have to pay more attention to [issues related to] financial toxicity and fertility, for example,” said Dr Hanna, who is the director of pediatric bone marrow transplantation at the clinic. (The term “financial toxicity” describes the cumulative negative impact of the high cost of care, lost work time, and delays in reaching educational and career goals on patients with cancer and their families.)

Another factor that likely contributes to the outcome disparities between AYAs and other populations with cancer is the relative lack of clinical trial involvement among AYAs.

A recent series of articles published in the journal Blood addressed these and other issues, among them, whether AYAs with acute lymphoblastic leukemia (ALL)¹ or aggressive B-cell non-Hodgkin lymphomas (NHLs) ² should be treated as children or adults; treatment strategies for those with acute myeloid leukemias (AMLs); ³ management of Hodgkin lymphoma;⁴ and psychosocial challenges and health-related quality of life (QoL) in AYAs with hematologic malignancies.⁵

In the introduction to the series, Jorge Cortes, MD, an assistant editor on the journal, wrote that hematologic malignancies in AYAs “represent a unique challenge because of their special biological features and distinctive therapeutic requirements, as well as the unique medical, social, and psychological characteristics of this patient population.”⁶

He noted, however, that “not much has been done to explore unique molecular and biological features of AYA hematologic malignancies. The discussion on the management of AYAs often centers on whether these patients should be treated in a pediatric setting or an adult setting, or with regimens designed for children or for adults,” noted Dr Cortes, professor and chair of the chronic myeloid leukemia section in the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston.
 

Therapeutic options: pediatric or adult protocols?

In their article on ALL in AYAs, Nicolas Boissel, MD, and André Baruchel, MD, note that the use of “fully pediatric protocols” in patients aged 15 through 20 years is supported by findings from numerous studies. In young adults, evidence increasingly supports “pediatric-inspired or even fully pediatric approaches” because they have been shown to significantly improve outcomes, with long-term survival rates nearing 70%.¹ Patients in these age groups require specific programs that factor in access to care and to trials, an increased risk of acute toxicities, and treatment adherence, which can be particularly problematic in AYAs, they concluded.

However, Kristen O’Dwyer, MD, and colleagues, argue in an article on AML treatment in AYAs that neither the pediatric nor adult approaches are ideally suited for AYAs because of the “distinguishing characteristics of AYAs with AML.” Rather, they conclude that AYA-specific approaches merit consideration.³

Similarly, Kieron Dunleavy, MD, and Thomas G Gross, MD, note in an article on managing aggressive B-cell NHLs in AYAs that there is a “remarkable divide” in the treatment of patients younger than 18 years with lymphoma compared with their young adult counterparts, and that it underscores the need for collaboration in developing consensus regarding treatment of AYAs.²
 

Clinical setting: pediatric or adult?

Consideration is also being given to the clinical setting in which AYA patients receive their treatment. Lori Muffly, MD, MS, and colleagues have reported that survival was superior for AYA patients with ALL who were treated in pediatric cancer settings,⁷ and other researchers have reported similar findings.

However, those improved outcomes in the pediatric setting might be offset by a higher use of resources and therefore higher costs, based on recent findings in a Canadian study by Paul C Nathan, MD, and colleagues.⁸ Among 1,356 patients aged 15-17 years who were diagnosed with cancer between 1996 and 2010, the authors found that the cost of care was higher when treatment took place in a pediatric setting compared with in an adult institution, and that it was driven in part by higher hospitalization rates and longer hospital stays. These findings were true across different diagnoses, including leukemias, lymphomas, sarcomas, and germ cell tumors, but only during the initial treatment phase.

In an accompanying editorial, Helen M Parsons, PhD, and her co-authors wrote that adolescents who receive treatment in the pediatric setting “tended to seek more [emergency department (ED)] care immediately before diagnosis and during the initial treatment phase; these adolescents also used more home care services during initial treatment and survivorship.⁹ They pointed out that the findings of higher inpatient days in the pediatric setting was not surprising given that induction therapies for pediatric ALL tend to be more complex and intensive than therapies commonly used in adults with ALL, and that pediatric cancer hospitals tend to have a wider array of services, including psychosocial and family support services.

“What is less clear is why individuals seen in pediatric settings have higher rates of ED care directly before diagnosis and during the initial treatment phase,” they wrote, adding that further investigation was needed on this topic to better understand those trends. “The finding that adolescents treated in pediatric institutions had higher resource use across diagnostic groups demonstrates that resource utilization may be driven just as much by care setting as diagnosis.” ⁹

The authors of the editorial emphasized that because of the differences in health care delivery and payment structures between the United States and Canada, where the Nathan study was done, it was important that similar studies are done in the United States to confirm these findings.
 

Disease and developmental biology

As Dr Hanna noted, biological differences and changes over time suggest that different age groups need varying approaches to treatment and that they may have different outcomes with the same treatments.

For example, the biology of AML is known to change with age, Dr O'Dwyer and her colleagues noted,³ citing a recent European study of 5,564 patients with de novo AML that showed that the frequency of favorable cytogenetics was low in infants (13.7%), increased in children (25%) and young adults (44%), and decreased again in middle age and older patients.¹⁰

“Most unfavorable cytogenetic abnormalities are rare across all age groups, though complex cytogenetics are relatively more frequent in infants, decrease in frequency in AYAs, and then increase in frequency beyond AYA,” Dr O'Dwyer and her colleagues wrote.³ It was also becoming more apparent that age influences the presence of AML-related molecular abnormalities, and recognition of age-related differences in disease biology “will provide the best opportunity to improve the clinical outcomes that have been static for decades.”

Dr Boissel and Dr Baruchel also noted in their report that light was finally being shed on the “black hole” of understanding ALL biology in AYAs, and research has shown that there is a continuum between childhood and adult ALL.¹ They concluded that “risk stratification based on recent biology findings and sequential [minimum residual disease] evaluations should now be implemented, as well as new therapeutic options including immunotherapy and targeted therapies, at best within the setting of integrated pediatric and AYA protocols.”
 

Psychosocial factors

“Cancer is a non-normative event for AYAs. It is extremely disruptive to them physically, psychologically, and vocationally ... and this poses significant challenges,” John Salsman, PhD, director of clinical research in AYA oncology at Wake Forest University, Winston-Salem, NC, said in an interview.

These patients have 5-year survival rates that haven’t improved in tandem with those in pediatric and adult populations over the last 3 decades, and in addition to the financial toxicity and strain, they also have higher rates of depression and anxiety, including fear of recurrence, he added. “Quality of life is incredibly important, and these things need to be addressed because of the developmental changes AYAs are navigating; there are issues of positive body image, family and career decisions ... these are challenging for anyone, and when you throw a cancer diagnosis into the mix they become disproportionately so.”

In a 2014 study, Dr Salsman and his colleagues found that AYAs with cancer had poorer physical and emotional quality of life when compared with matched controls, but better social quality of life.¹¹ The latter finding was surprising and highlights the importance of the social dimension in the lives of AYAs. “Patient after patient will say ‘I found out who my real friends are,’  ” he said. “There’s this refinement and deepening of the social network among some posttreatment survivors.”

Dr Salsman and his colleagues are using those findings to develop interventions that can maximize self-care in posttreatment survivorship – a time when AYAs may feel they have a new lease on life and may be more motivated to adhere to recommendations and take care of themselves. For example, a randomized controlled pilot study that incorporates social media apps and other technologies to build on the positive social components of their lives in promoting physical activity interventions is underway.

Another intervention targets emotional well-being through the use of web-based tools to increase positive affect. A proof-of-concept study showed that the approach was feasible and well received, and a larger-scale randomized controlled trial is being planned, he said.

Dr Salsman also praised the PRISM (Promoting Resilience in Stress Management) tool developed by researchers at Seattle Children’s Hospital. It was created to help AYAs with cancer and other illnesses learn coping skills to manage stress after their diagnosis and to boost quality of life beyond treatment. A digital app has also been developed to be used in conjunction with the program.
 

Trial enrollment

In his editorial introducing the Blood series on AYAs and cancer, Dr Cortes noted a paucity of clinical trials specifically designed for this population. “At the time of this writing, I could identify four therapeutic trials registered at www.clinicaltrials.gov that appeared to be somewhat specifically designed for AYAs (some included children also),” he wrote, describing AYA enrollment in clinical trials in cancer as “suboptimal at best.”⁶

Dr Salsman said these dismal enrolment numbers could in part be related to treatment setting. Data suggest that most AYAs with cancer are treated in community-based practices rather than comprehensive cancer centers where the bulk of research is being done, he explained.

Dr Hanna agreed that more research involving AYAs was needed as is a better understanding of why enrollment is so much lower in this population. He pointed out that in 2017 the American Society of Clinical Oncology and Friends of Cancer Research released a statement recommending that pediatric patients be considered for enrollment in later-phase trials for cancer types that span both adults and children.¹² The organizations said that individuals aged 12 years and older should routinely be included in such trials because their drug metabolism is similar to adults, and inclusion of younger patients may also be appropriate if they are part of the population affected by the disease, depending on specific disease biology, action of the drug, and available safety information.

Officials at the Food and Drug Administration are considering that possibility, Dr Hanna said.

Dr Salsman added there has been an increase in recent years in the attention paid to disparities in survival improvements and trial involvement among AYAs with cancer, compared with other age groups. For example, about 5 years ago, the National Clinical Trials Network formed a working group that developed a number of specific objectives for incorporating more AYAs into cancer trials and finding better ways to study this population;¹³ the Institute of Medicine held a forum on the care of AYAs with cancer;¹⁴ and the National Cancer Institute held a state-of-the-science meeting that focused on identifying strategic priorities for AYA oncology,¹⁵ he noted.

Dr Hanna added that “scientific groups such as Southwest Oncology Group (SWOG) and Children’s Oncology Group (COG) also have AYA committees now. One of the success stories of working together between SWOG and COG was the intergroup study C10403 for patients with ALL. And now there are efforts for an intergroup AYA-AML task force to include representatives from each of the cooperative groups that historically co-ordinated myeloid disease clinical trials – COG, SWOG, Alliance, and ECOG-ACRIN,” he said.

In fact, all of the National Clinical Trials Network groups have some initiative in place to address AYA concerns, said Dr Salsman, who chairs the ECOG-ACRIN AYA oncology subcommittee.

Despite these efforts, and many others, long-term survival improvements among AYAs with cancer still fall short, compared with those of other age groups.¹⁶

Next steps

Among the recommendations from authors in the AYA series in Blood is a call for assessing AYA-specific therapy in future clinical trials, as well as improved collaboration between adult and pediatric teams and the involvement of multidisciplinary teams in care for this population.

Many centers are already working on models for collaborative care, Dr Salsman said, citing the Fort Worth AYA Oncology Coalition led by medical director Karen Albritton, MD, as an example of a program that has been successful in helping clinical and supportive caregivers and their AYA patients “have a shared vision” as they work to maximize improvements in outcomes.

Patients are also taking the lead in demanding better care and attention to their psychosocial needs, Dr Hanna said. In the case of the community-powered advocacy organization Critical Mass, members have succeeded in getting lawmakers to introduce a bill in the US House of Representatives that would allow college students to defer loan payments while undergoing cancer treatment.

Survival gains among adolescents and young adults (AYAs) with cancer continue to lag behind outcomes for children and older adult patients. It’s a trend that spans decades, but clinicians and researchers are finally getting serious about trying to understand the underlying causes and are re-examining prevailing practices in an effort to address the discrepancies.

“This is a very heterogeneous group of disorders,” Rabi Hanna, MD, a pediatric hematologist and oncologist at Cleveland Clinic Children’s Hospital, Ohio, said in an interview. He’s specifically referring to the cancers that affect AYAs, who are broadly defined as patients aged 15 through 39 years. “A few cancers, such as [acute lymphoblastic leukemia], are more common in children, and others, such as breast cancer, are more common in adults. The biology may be different in the adolescent and young adult patients, which may lead to different outcomes.”

In addition, the psychosocial needs in this age group differ vastly from those in other groups. “Many of these patients are in college or have just started their families, so we have to pay more attention to [issues related to] financial toxicity and fertility, for example,” said Dr Hanna, who is the director of pediatric bone marrow transplantation at the clinic. (The term “financial toxicity” describes the cumulative negative impact of the high cost of care, lost work time, and delays in reaching educational and career goals on patients with cancer and their families.)

Another factor that likely contributes to the outcome disparities between AYAs and other populations with cancer is the relative lack of clinical trial involvement among AYAs.

A recent series of articles published in the journal Blood addressed these and other issues, among them, whether AYAs with acute lymphoblastic leukemia (ALL)¹ or aggressive B-cell non-Hodgkin lymphomas (NHLs) ² should be treated as children or adults; treatment strategies for those with acute myeloid leukemias (AMLs); ³ management of Hodgkin lymphoma;⁴ and psychosocial challenges and health-related quality of life (QoL) in AYAs with hematologic malignancies.⁵

In the introduction to the series, Jorge Cortes, MD, an assistant editor on the journal, wrote that hematologic malignancies in AYAs “represent a unique challenge because of their special biological features and distinctive therapeutic requirements, as well as the unique medical, social, and psychological characteristics of this patient population.”⁶

He noted, however, that “not much has been done to explore unique molecular and biological features of AYA hematologic malignancies. The discussion on the management of AYAs often centers on whether these patients should be treated in a pediatric setting or an adult setting, or with regimens designed for children or for adults,” noted Dr Cortes, professor and chair of the chronic myeloid leukemia section in the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston.
 

Therapeutic options: pediatric or adult protocols?

In their article on ALL in AYAs, Nicolas Boissel, MD, and André Baruchel, MD, note that the use of “fully pediatric protocols” in patients aged 15 through 20 years is supported by findings from numerous studies. In young adults, evidence increasingly supports “pediatric-inspired or even fully pediatric approaches” because they have been shown to significantly improve outcomes, with long-term survival rates nearing 70%.¹ Patients in these age groups require specific programs that factor in access to care and to trials, an increased risk of acute toxicities, and treatment adherence, which can be particularly problematic in AYAs, they concluded.

However, Kristen O’Dwyer, MD, and colleagues, argue in an article on AML treatment in AYAs that neither the pediatric nor adult approaches are ideally suited for AYAs because of the “distinguishing characteristics of AYAs with AML.” Rather, they conclude that AYA-specific approaches merit consideration.³

Similarly, Kieron Dunleavy, MD, and Thomas G Gross, MD, note in an article on managing aggressive B-cell NHLs in AYAs that there is a “remarkable divide” in the treatment of patients younger than 18 years with lymphoma compared with their young adult counterparts, and that it underscores the need for collaboration in developing consensus regarding treatment of AYAs.²
 

Clinical setting: pediatric or adult?

Consideration is also being given to the clinical setting in which AYA patients receive their treatment. Lori Muffly, MD, MS, and colleagues have reported that survival was superior for AYA patients with ALL who were treated in pediatric cancer settings,⁷ and other researchers have reported similar findings.

However, those improved outcomes in the pediatric setting might be offset by a higher use of resources and therefore higher costs, based on recent findings in a Canadian study by Paul C Nathan, MD, and colleagues.⁸ Among 1,356 patients aged 15-17 years who were diagnosed with cancer between 1996 and 2010, the authors found that the cost of care was higher when treatment took place in a pediatric setting compared with in an adult institution, and that it was driven in part by higher hospitalization rates and longer hospital stays. These findings were true across different diagnoses, including leukemias, lymphomas, sarcomas, and germ cell tumors, but only during the initial treatment phase.

In an accompanying editorial, Helen M Parsons, PhD, and her co-authors wrote that adolescents who receive treatment in the pediatric setting “tended to seek more [emergency department (ED)] care immediately before diagnosis and during the initial treatment phase; these adolescents also used more home care services during initial treatment and survivorship.⁹ They pointed out that the findings of higher inpatient days in the pediatric setting was not surprising given that induction therapies for pediatric ALL tend to be more complex and intensive than therapies commonly used in adults with ALL, and that pediatric cancer hospitals tend to have a wider array of services, including psychosocial and family support services.

“What is less clear is why individuals seen in pediatric settings have higher rates of ED care directly before diagnosis and during the initial treatment phase,” they wrote, adding that further investigation was needed on this topic to better understand those trends. “The finding that adolescents treated in pediatric institutions had higher resource use across diagnostic groups demonstrates that resource utilization may be driven just as much by care setting as diagnosis.” ⁹

The authors of the editorial emphasized that because of the differences in health care delivery and payment structures between the United States and Canada, where the Nathan study was done, it was important that similar studies are done in the United States to confirm these findings.
 

Disease and developmental biology

As Dr Hanna noted, biological differences and changes over time suggest that different age groups need varying approaches to treatment and that they may have different outcomes with the same treatments.

For example, the biology of AML is known to change with age, Dr O'Dwyer and her colleagues noted,³ citing a recent European study of 5,564 patients with de novo AML that showed that the frequency of favorable cytogenetics was low in infants (13.7%), increased in children (25%) and young adults (44%), and decreased again in middle age and older patients.¹⁰

“Most unfavorable cytogenetic abnormalities are rare across all age groups, though complex cytogenetics are relatively more frequent in infants, decrease in frequency in AYAs, and then increase in frequency beyond AYA,” Dr O'Dwyer and her colleagues wrote.³ It was also becoming more apparent that age influences the presence of AML-related molecular abnormalities, and recognition of age-related differences in disease biology “will provide the best opportunity to improve the clinical outcomes that have been static for decades.”

Dr Boissel and Dr Baruchel also noted in their report that light was finally being shed on the “black hole” of understanding ALL biology in AYAs, and research has shown that there is a continuum between childhood and adult ALL.¹ They concluded that “risk stratification based on recent biology findings and sequential [minimum residual disease] evaluations should now be implemented, as well as new therapeutic options including immunotherapy and targeted therapies, at best within the setting of integrated pediatric and AYA protocols.”
 

Psychosocial factors

“Cancer is a non-normative event for AYAs. It is extremely disruptive to them physically, psychologically, and vocationally ... and this poses significant challenges,” John Salsman, PhD, director of clinical research in AYA oncology at Wake Forest University, Winston-Salem, NC, said in an interview.

These patients have 5-year survival rates that haven’t improved in tandem with those in pediatric and adult populations over the last 3 decades, and in addition to the financial toxicity and strain, they also have higher rates of depression and anxiety, including fear of recurrence, he added. “Quality of life is incredibly important, and these things need to be addressed because of the developmental changes AYAs are navigating; there are issues of positive body image, family and career decisions ... these are challenging for anyone, and when you throw a cancer diagnosis into the mix they become disproportionately so.”

In a 2014 study, Dr Salsman and his colleagues found that AYAs with cancer had poorer physical and emotional quality of life when compared with matched controls, but better social quality of life.¹¹ The latter finding was surprising and highlights the importance of the social dimension in the lives of AYAs. “Patient after patient will say ‘I found out who my real friends are,’  ” he said. “There’s this refinement and deepening of the social network among some posttreatment survivors.”

Dr Salsman and his colleagues are using those findings to develop interventions that can maximize self-care in posttreatment survivorship – a time when AYAs may feel they have a new lease on life and may be more motivated to adhere to recommendations and take care of themselves. For example, a randomized controlled pilot study that incorporates social media apps and other technologies to build on the positive social components of their lives in promoting physical activity interventions is underway.

Another intervention targets emotional well-being through the use of web-based tools to increase positive affect. A proof-of-concept study showed that the approach was feasible and well received, and a larger-scale randomized controlled trial is being planned, he said.

Dr Salsman also praised the PRISM (Promoting Resilience in Stress Management) tool developed by researchers at Seattle Children’s Hospital. It was created to help AYAs with cancer and other illnesses learn coping skills to manage stress after their diagnosis and to boost quality of life beyond treatment. A digital app has also been developed to be used in conjunction with the program.
 

Trial enrollment

In his editorial introducing the Blood series on AYAs and cancer, Dr Cortes noted a paucity of clinical trials specifically designed for this population. “At the time of this writing, I could identify four therapeutic trials registered at www.clinicaltrials.gov that appeared to be somewhat specifically designed for AYAs (some included children also),” he wrote, describing AYA enrollment in clinical trials in cancer as “suboptimal at best.”⁶

Dr Salsman said these dismal enrolment numbers could in part be related to treatment setting. Data suggest that most AYAs with cancer are treated in community-based practices rather than comprehensive cancer centers where the bulk of research is being done, he explained.

Dr Hanna agreed that more research involving AYAs was needed as is a better understanding of why enrollment is so much lower in this population. He pointed out that in 2017 the American Society of Clinical Oncology and Friends of Cancer Research released a statement recommending that pediatric patients be considered for enrollment in later-phase trials for cancer types that span both adults and children.¹² The organizations said that individuals aged 12 years and older should routinely be included in such trials because their drug metabolism is similar to adults, and inclusion of younger patients may also be appropriate if they are part of the population affected by the disease, depending on specific disease biology, action of the drug, and available safety information.

Officials at the Food and Drug Administration are considering that possibility, Dr Hanna said.

Dr Salsman added there has been an increase in recent years in the attention paid to disparities in survival improvements and trial involvement among AYAs with cancer, compared with other age groups. For example, about 5 years ago, the National Clinical Trials Network formed a working group that developed a number of specific objectives for incorporating more AYAs into cancer trials and finding better ways to study this population;¹³ the Institute of Medicine held a forum on the care of AYAs with cancer;¹⁴ and the National Cancer Institute held a state-of-the-science meeting that focused on identifying strategic priorities for AYA oncology,¹⁵ he noted.

Dr Hanna added that “scientific groups such as Southwest Oncology Group (SWOG) and Children’s Oncology Group (COG) also have AYA committees now. One of the success stories of working together between SWOG and COG was the intergroup study C10403 for patients with ALL. And now there are efforts for an intergroup AYA-AML task force to include representatives from each of the cooperative groups that historically co-ordinated myeloid disease clinical trials – COG, SWOG, Alliance, and ECOG-ACRIN,” he said.

In fact, all of the National Clinical Trials Network groups have some initiative in place to address AYA concerns, said Dr Salsman, who chairs the ECOG-ACRIN AYA oncology subcommittee.

Despite these efforts, and many others, long-term survival improvements among AYAs with cancer still fall short, compared with those of other age groups.¹⁶

Next steps

Among the recommendations from authors in the AYA series in Blood is a call for assessing AYA-specific therapy in future clinical trials, as well as improved collaboration between adult and pediatric teams and the involvement of multidisciplinary teams in care for this population.

Many centers are already working on models for collaborative care, Dr Salsman said, citing the Fort Worth AYA Oncology Coalition led by medical director Karen Albritton, MD, as an example of a program that has been successful in helping clinical and supportive caregivers and their AYA patients “have a shared vision” as they work to maximize improvements in outcomes.

Patients are also taking the lead in demanding better care and attention to their psychosocial needs, Dr Hanna said. In the case of the community-powered advocacy organization Critical Mass, members have succeeded in getting lawmakers to introduce a bill in the US House of Representatives that would allow college students to defer loan payments while undergoing cancer treatment.

Survival gains among adolescents and young adults (AYAs) with cancer continue to lag behind outcomes for children and older adult patients. It’s a trend that spans decades, but clinicians and researchers are finally getting serious about trying to understand the underlying causes and are re-examining prevailing practices in an effort to address the discrepancies.

“This is a very heterogeneous group of disorders,” Rabi Hanna, MD, a pediatric hematologist and oncologist at Cleveland Clinic Children’s Hospital, Ohio, said in an interview. He’s specifically referring to the cancers that affect AYAs, who are broadly defined as patients aged 15 through 39 years. “A few cancers, such as [acute lymphoblastic leukemia], are more common in children, and others, such as breast cancer, are more common in adults. The biology may be different in the adolescent and young adult patients, which may lead to different outcomes.”

In addition, the psychosocial needs in this age group differ vastly from those in other groups. “Many of these patients are in college or have just started their families, so we have to pay more attention to [issues related to] financial toxicity and fertility, for example,” said Dr Hanna, who is the director of pediatric bone marrow transplantation at the clinic. (The term “financial toxicity” describes the cumulative negative impact of the high cost of care, lost work time, and delays in reaching educational and career goals on patients with cancer and their families.)

Another factor that likely contributes to the outcome disparities between AYAs and other populations with cancer is the relative lack of clinical trial involvement among AYAs.

A recent series of articles published in the journal Blood addressed these and other issues, among them, whether AYAs with acute lymphoblastic leukemia (ALL)¹ or aggressive B-cell non-Hodgkin lymphomas (NHLs) ² should be treated as children or adults; treatment strategies for those with acute myeloid leukemias (AMLs); ³ management of Hodgkin lymphoma;⁴ and psychosocial challenges and health-related quality of life (QoL) in AYAs with hematologic malignancies.⁵

In the introduction to the series, Jorge Cortes, MD, an assistant editor on the journal, wrote that hematologic malignancies in AYAs “represent a unique challenge because of their special biological features and distinctive therapeutic requirements, as well as the unique medical, social, and psychological characteristics of this patient population.”⁶

He noted, however, that “not much has been done to explore unique molecular and biological features of AYA hematologic malignancies. The discussion on the management of AYAs often centers on whether these patients should be treated in a pediatric setting or an adult setting, or with regimens designed for children or for adults,” noted Dr Cortes, professor and chair of the chronic myeloid leukemia section in the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston.
 

Therapeutic options: pediatric or adult protocols?

In their article on ALL in AYAs, Nicolas Boissel, MD, and André Baruchel, MD, note that the use of “fully pediatric protocols” in patients aged 15 through 20 years is supported by findings from numerous studies. In young adults, evidence increasingly supports “pediatric-inspired or even fully pediatric approaches” because they have been shown to significantly improve outcomes, with long-term survival rates nearing 70%.¹ Patients in these age groups require specific programs that factor in access to care and to trials, an increased risk of acute toxicities, and treatment adherence, which can be particularly problematic in AYAs, they concluded.

However, Kristen O’Dwyer, MD, and colleagues, argue in an article on AML treatment in AYAs that neither the pediatric nor adult approaches are ideally suited for AYAs because of the “distinguishing characteristics of AYAs with AML.” Rather, they conclude that AYA-specific approaches merit consideration.³

Similarly, Kieron Dunleavy, MD, and Thomas G Gross, MD, note in an article on managing aggressive B-cell NHLs in AYAs that there is a “remarkable divide” in the treatment of patients younger than 18 years with lymphoma compared with their young adult counterparts, and that it underscores the need for collaboration in developing consensus regarding treatment of AYAs.²
 

Clinical setting: pediatric or adult?

Consideration is also being given to the clinical setting in which AYA patients receive their treatment. Lori Muffly, MD, MS, and colleagues have reported that survival was superior for AYA patients with ALL who were treated in pediatric cancer settings,⁷ and other researchers have reported similar findings.

However, those improved outcomes in the pediatric setting might be offset by a higher use of resources and therefore higher costs, based on recent findings in a Canadian study by Paul C Nathan, MD, and colleagues.⁸ Among 1,356 patients aged 15-17 years who were diagnosed with cancer between 1996 and 2010, the authors found that the cost of care was higher when treatment took place in a pediatric setting compared with in an adult institution, and that it was driven in part by higher hospitalization rates and longer hospital stays. These findings were true across different diagnoses, including leukemias, lymphomas, sarcomas, and germ cell tumors, but only during the initial treatment phase.

In an accompanying editorial, Helen M Parsons, PhD, and her co-authors wrote that adolescents who receive treatment in the pediatric setting “tended to seek more [emergency department (ED)] care immediately before diagnosis and during the initial treatment phase; these adolescents also used more home care services during initial treatment and survivorship.⁹ They pointed out that the findings of higher inpatient days in the pediatric setting was not surprising given that induction therapies for pediatric ALL tend to be more complex and intensive than therapies commonly used in adults with ALL, and that pediatric cancer hospitals tend to have a wider array of services, including psychosocial and family support services.

“What is less clear is why individuals seen in pediatric settings have higher rates of ED care directly before diagnosis and during the initial treatment phase,” they wrote, adding that further investigation was needed on this topic to better understand those trends. “The finding that adolescents treated in pediatric institutions had higher resource use across diagnostic groups demonstrates that resource utilization may be driven just as much by care setting as diagnosis.” ⁹

The authors of the editorial emphasized that because of the differences in health care delivery and payment structures between the United States and Canada, where the Nathan study was done, it was important that similar studies are done in the United States to confirm these findings.
 

Disease and developmental biology

As Dr Hanna noted, biological differences and changes over time suggest that different age groups need varying approaches to treatment and that they may have different outcomes with the same treatments.

For example, the biology of AML is known to change with age, Dr O'Dwyer and her colleagues noted,³ citing a recent European study of 5,564 patients with de novo AML that showed that the frequency of favorable cytogenetics was low in infants (13.7%), increased in children (25%) and young adults (44%), and decreased again in middle age and older patients.¹⁰

“Most unfavorable cytogenetic abnormalities are rare across all age groups, though complex cytogenetics are relatively more frequent in infants, decrease in frequency in AYAs, and then increase in frequency beyond AYA,” Dr O'Dwyer and her colleagues wrote.³ It was also becoming more apparent that age influences the presence of AML-related molecular abnormalities, and recognition of age-related differences in disease biology “will provide the best opportunity to improve the clinical outcomes that have been static for decades.”

Dr Boissel and Dr Baruchel also noted in their report that light was finally being shed on the “black hole” of understanding ALL biology in AYAs, and research has shown that there is a continuum between childhood and adult ALL.¹ They concluded that “risk stratification based on recent biology findings and sequential [minimum residual disease] evaluations should now be implemented, as well as new therapeutic options including immunotherapy and targeted therapies, at best within the setting of integrated pediatric and AYA protocols.”
 

Psychosocial factors

“Cancer is a non-normative event for AYAs. It is extremely disruptive to them physically, psychologically, and vocationally ... and this poses significant challenges,” John Salsman, PhD, director of clinical research in AYA oncology at Wake Forest University, Winston-Salem, NC, said in an interview.

These patients have 5-year survival rates that haven’t improved in tandem with those in pediatric and adult populations over the last 3 decades, and in addition to the financial toxicity and strain, they also have higher rates of depression and anxiety, including fear of recurrence, he added. “Quality of life is incredibly important, and these things need to be addressed because of the developmental changes AYAs are navigating; there are issues of positive body image, family and career decisions ... these are challenging for anyone, and when you throw a cancer diagnosis into the mix they become disproportionately so.”

In a 2014 study, Dr Salsman and his colleagues found that AYAs with cancer had poorer physical and emotional quality of life when compared with matched controls, but better social quality of life.¹¹ The latter finding was surprising and highlights the importance of the social dimension in the lives of AYAs. “Patient after patient will say ‘I found out who my real friends are,’  ” he said. “There’s this refinement and deepening of the social network among some posttreatment survivors.”

Dr Salsman and his colleagues are using those findings to develop interventions that can maximize self-care in posttreatment survivorship – a time when AYAs may feel they have a new lease on life and may be more motivated to adhere to recommendations and take care of themselves. For example, a randomized controlled pilot study that incorporates social media apps and other technologies to build on the positive social components of their lives in promoting physical activity interventions is underway.

Another intervention targets emotional well-being through the use of web-based tools to increase positive affect. A proof-of-concept study showed that the approach was feasible and well received, and a larger-scale randomized controlled trial is being planned, he said.

Dr Salsman also praised the PRISM (Promoting Resilience in Stress Management) tool developed by researchers at Seattle Children’s Hospital. It was created to help AYAs with cancer and other illnesses learn coping skills to manage stress after their diagnosis and to boost quality of life beyond treatment. A digital app has also been developed to be used in conjunction with the program.
 

Trial enrollment

In his editorial introducing the Blood series on AYAs and cancer, Dr Cortes noted a paucity of clinical trials specifically designed for this population. “At the time of this writing, I could identify four therapeutic trials registered at www.clinicaltrials.gov that appeared to be somewhat specifically designed for AYAs (some included children also),” he wrote, describing AYA enrollment in clinical trials in cancer as “suboptimal at best.”⁶

Dr Salsman said these dismal enrolment numbers could in part be related to treatment setting. Data suggest that most AYAs with cancer are treated in community-based practices rather than comprehensive cancer centers where the bulk of research is being done, he explained.

Dr Hanna agreed that more research involving AYAs was needed as is a better understanding of why enrollment is so much lower in this population. He pointed out that in 2017 the American Society of Clinical Oncology and Friends of Cancer Research released a statement recommending that pediatric patients be considered for enrollment in later-phase trials for cancer types that span both adults and children.¹² The organizations said that individuals aged 12 years and older should routinely be included in such trials because their drug metabolism is similar to adults, and inclusion of younger patients may also be appropriate if they are part of the population affected by the disease, depending on specific disease biology, action of the drug, and available safety information.

Officials at the Food and Drug Administration are considering that possibility, Dr Hanna said.

Dr Salsman added there has been an increase in recent years in the attention paid to disparities in survival improvements and trial involvement among AYAs with cancer, compared with other age groups. For example, about 5 years ago, the National Clinical Trials Network formed a working group that developed a number of specific objectives for incorporating more AYAs into cancer trials and finding better ways to study this population;¹³ the Institute of Medicine held a forum on the care of AYAs with cancer;¹⁴ and the National Cancer Institute held a state-of-the-science meeting that focused on identifying strategic priorities for AYA oncology,¹⁵ he noted.

Dr Hanna added that “scientific groups such as Southwest Oncology Group (SWOG) and Children’s Oncology Group (COG) also have AYA committees now. One of the success stories of working together between SWOG and COG was the intergroup study C10403 for patients with ALL. And now there are efforts for an intergroup AYA-AML task force to include representatives from each of the cooperative groups that historically co-ordinated myeloid disease clinical trials – COG, SWOG, Alliance, and ECOG-ACRIN,” he said.

In fact, all of the National Clinical Trials Network groups have some initiative in place to address AYA concerns, said Dr Salsman, who chairs the ECOG-ACRIN AYA oncology subcommittee.

Despite these efforts, and many others, long-term survival improvements among AYAs with cancer still fall short, compared with those of other age groups.¹⁶

Next steps

Among the recommendations from authors in the AYA series in Blood is a call for assessing AYA-specific therapy in future clinical trials, as well as improved collaboration between adult and pediatric teams and the involvement of multidisciplinary teams in care for this population.

Many centers are already working on models for collaborative care, Dr Salsman said, citing the Fort Worth AYA Oncology Coalition led by medical director Karen Albritton, MD, as an example of a program that has been successful in helping clinical and supportive caregivers and their AYA patients “have a shared vision” as they work to maximize improvements in outcomes.

Patients are also taking the lead in demanding better care and attention to their psychosocial needs, Dr Hanna said. In the case of the community-powered advocacy organization Critical Mass, members have succeeded in getting lawmakers to introduce a bill in the US House of Representatives that would allow college students to defer loan payments while undergoing cancer treatment.

The Society for Pediatric Dermatology (SPD) was established in 1975, and the pediatric dermatology workforce shortage began shortly after. In 1986, Honig and Burke¹ reported that opportunities in pediatric dermatology were limited and that pediatric dermatologists were predominantly located in larger teaching hospitals and selected private practice settings; furthermore, only approximately 20% had patient populations comprising more than 75% children.¹ Positive changes have occurred since that time, with more practitioners dedicated to pediatric dermatology and increased opportunities within the specialty. The SPD has expanded to a thriving group of collegial pediatric dermatologists now topping 1200 members worldwide.

Although the SPD has strongly influenced practice development in pediatric dermatology, there are fewer than 300 board-certified pediatric dermatologists in the United States and approximately double that number of pediatric dermatology practitioners. The deficiency is glaring based on the national population alone. The US Census Bureau reported 325,719,178 individuals living in the United States (as of July 1, 2017).² With approximately 75 million children in the United States and estimates that 22.8% of the population is younger than 18 years,³ there currently is 1 pediatric dermatologist for every 120,000 children or more.

As if the numbers alone were not adequate, a number of publications have addressed the benefits of pediatric dermatologists in both dermatology and pediatrics training and furthermore in pediatric care. A 2004 survey of dermatology program directors and chairpersons regarding the issue of the pediatric dermatology workforce shortage revealed that 45 of 94 (47.9%) programs employed a pediatric dermatologist and 24 (25.5%) had been looking to hire one for more than a year.⁴ Although more pediatric dermatologists have joined the workforce, it is not surprising that programs with no pediatric dermatologists want them. First, pediatric dermatologists dramatically improve the quality of training with regard to pediatric dermatology education and can increase dermatology residents’ comfort level with children. In a survey of a group of graduating third-year dermatology residents, dermatology residency program directors, and pediatric dermatology fellowship program directors by Nijhawan et al,⁵ residents who were trained in a program with one or more full-time pediatric dermatologists were more likely to feel competent treating children and to feel satisfied with their training program’s pediatric dermatology curriculum than residents without contact with a full-time pediatric dermatologist (50.0% vs 5.9% [P=.002] and 85.3% vs 52.9% [P<.001], respectively). The availability of a pediatric dermatology fellowship further enhanced satisfaction. Residents in programs with no full-time pediatric dermatologist on staff were more likely to be somewhat or extremely dissatisfied with their pediatric dermatology training. Residency program directors were more satisfied with their curriculums when there was one or more pediatric dermatologist on staff (P<.01).⁵

Programs with pediatric dermatologists also offer easy access to a mentor in the field. In a 2010 survey of pediatric dermatologists (published in 2014), Admani et al⁶ reported that 84% (91/109) of respondents (board-certified pediatric dermatologists) cited mentorship as the most important factor influencing their career choice. Exposure to the specialty was noted as a key motivating factor. In my opinion, the actual inclusion of a pediatric dermatology fellowship, whether the position is filled or not, appears to increase the chances of expansion and retention in the field. In the 2014 SPD workforce survey, more than 62% (61/98) of respondents were fellowship trained.⁷ In 2004 there were only 6 pediatric dermatology fellowship training programs. We have come quite far now with 36 fellowships as of August 12, 2018.⁸ The cost of education of course is not simple when pediatric dermatology fellowships are unfunded by the Accreditation Council for Graduate Medical Education; however, it is clear that the initial investment can create ongoing returns in pediatric dermatology.

Furthermore, due to the outpatient burden of skin disease in a pediatrics practice, providing pediatric trainees with contact with a pediatric dermatologist is needed. Prindaville et al⁹ performed a review from 2006 through 2010 of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey databases, which revealed that 9% of 23 million pediatric visits during this time period were for dermatologic diseases; therefore, knowledge of pediatric dermatology is vital to pediatrician training.

As if there was not enough evidence that pediatric dermatologists are in high demand, SPD pediatric dermatology workforce surveys from the last 5 years, which will soon be updated, show similar indications.^7,10 Fogel and Teng¹¹ showed that 60% of surveyed pediatric dermatologists (N=226) were academic and 81% were salaried. Unlike previous data,¹ the investigators showed that children constituted 79.5% of respondents’ patient populations. The academic practice environment favored by the majority of pediatric dermatologists was associated with seeing fewer patients per week and longer wait times (approximately 60 days for a pediatric dermatologist vs 15 days in other practice environments).¹¹ Therefore, the demand continues to be unmet even in many institutions with pediatric dermatology practitioners in place.

For the medical student or resident seeking a career in pediatric dermatology, it appears that finding and working on projects with mentors likely is the key to stepping in the field. From my own experience, pediatric dermatologists are extremely friendly and open to supporting career development in earnest students. Reach out to potential mentors months before starting desired electives, as you are competing with other students and pediatrics, dermatology, and emergency medicine residents. Joining and attending meetings of the SPD is a great way to find direction in this friendly and collegial field. Additionally, pediatric dermatology sessions at the annual meetings of the American Academy of Dermatology are a wonderful way to experience the excitement of the field. As a pediatric dermatologist in practice for almost 2 decades, I can honestly say that the field is always intellectually stimulating and evolving rapidly through enhanced understanding of disease pathogenesis, genetics, and therapeutics. Helping children and their parents/guardians never gets boring.

The solution to improving the size and accessibility of the pediatric dermatology workforce is not simple and likely starts from the bottom up. More than 75% of pediatric dermatologists favor implementing systems to encourage medical students to pursue a career in pediatric dermatology.⁷ Increasing resident exposure to dedicated pediatric dermatology training time enhances satisfaction.⁵ Increased funding of fellowships can help these students and residents meet their goals. Current fellowship training programs now total 36, but not all approved institutions have been able to support a postgraduate year 5 (PGY-5) or higher fellow, and in my experience some institutions have avoided adding a fellow due to lack of funding internally. The average pediatric dermatologist earns $100,000 less than colleagues who treat adults, which is an impediment to the expansion of the field.¹⁰ This disparity may chase away practitioners, especially those with medical school debt. Debt forgiveness programs, enhanced practice development, and better base pay for pediatric dermatologists could positively impact growth in this specialty. Dermatology and pediatrics training programs need to dedicate more money and developmental support for pediatric dermatologists as a way to invest in the quality of pediatric dermatology education for their trainees. By recognizing the true value of the academic contributions of pediatric dermatologists, dermatology residency programs can invest in producing trainees with greater aplomb and acumen in pediatric dermatology.

The Society for Pediatric Dermatology (SPD) was established in 1975, and the pediatric dermatology workforce shortage began shortly after. In 1986, Honig and Burke¹ reported that opportunities in pediatric dermatology were limited and that pediatric dermatologists were predominantly located in larger teaching hospitals and selected private practice settings; furthermore, only approximately 20% had patient populations comprising more than 75% children.¹ Positive changes have occurred since that time, with more practitioners dedicated to pediatric dermatology and increased opportunities within the specialty. The SPD has expanded to a thriving group of collegial pediatric dermatologists now topping 1200 members worldwide.

Although the SPD has strongly influenced practice development in pediatric dermatology, there are fewer than 300 board-certified pediatric dermatologists in the United States and approximately double that number of pediatric dermatology practitioners. The deficiency is glaring based on the national population alone. The US Census Bureau reported 325,719,178 individuals living in the United States (as of July 1, 2017).² With approximately 75 million children in the United States and estimates that 22.8% of the population is younger than 18 years,³ there currently is 1 pediatric dermatologist for every 120,000 children or more.

As if the numbers alone were not adequate, a number of publications have addressed the benefits of pediatric dermatologists in both dermatology and pediatrics training and furthermore in pediatric care. A 2004 survey of dermatology program directors and chairpersons regarding the issue of the pediatric dermatology workforce shortage revealed that 45 of 94 (47.9%) programs employed a pediatric dermatologist and 24 (25.5%) had been looking to hire one for more than a year.⁴ Although more pediatric dermatologists have joined the workforce, it is not surprising that programs with no pediatric dermatologists want them. First, pediatric dermatologists dramatically improve the quality of training with regard to pediatric dermatology education and can increase dermatology residents’ comfort level with children. In a survey of a group of graduating third-year dermatology residents, dermatology residency program directors, and pediatric dermatology fellowship program directors by Nijhawan et al,⁵ residents who were trained in a program with one or more full-time pediatric dermatologists were more likely to feel competent treating children and to feel satisfied with their training program’s pediatric dermatology curriculum than residents without contact with a full-time pediatric dermatologist (50.0% vs 5.9% [P=.002] and 85.3% vs 52.9% [P<.001], respectively). The availability of a pediatric dermatology fellowship further enhanced satisfaction. Residents in programs with no full-time pediatric dermatologist on staff were more likely to be somewhat or extremely dissatisfied with their pediatric dermatology training. Residency program directors were more satisfied with their curriculums when there was one or more pediatric dermatologist on staff (P<.01).⁵

Programs with pediatric dermatologists also offer easy access to a mentor in the field. In a 2010 survey of pediatric dermatologists (published in 2014), Admani et al⁶ reported that 84% (91/109) of respondents (board-certified pediatric dermatologists) cited mentorship as the most important factor influencing their career choice. Exposure to the specialty was noted as a key motivating factor. In my opinion, the actual inclusion of a pediatric dermatology fellowship, whether the position is filled or not, appears to increase the chances of expansion and retention in the field. In the 2014 SPD workforce survey, more than 62% (61/98) of respondents were fellowship trained.⁷ In 2004 there were only 6 pediatric dermatology fellowship training programs. We have come quite far now with 36 fellowships as of August 12, 2018.⁸ The cost of education of course is not simple when pediatric dermatology fellowships are unfunded by the Accreditation Council for Graduate Medical Education; however, it is clear that the initial investment can create ongoing returns in pediatric dermatology.

Furthermore, due to the outpatient burden of skin disease in a pediatrics practice, providing pediatric trainees with contact with a pediatric dermatologist is needed. Prindaville et al⁹ performed a review from 2006 through 2010 of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey databases, which revealed that 9% of 23 million pediatric visits during this time period were for dermatologic diseases; therefore, knowledge of pediatric dermatology is vital to pediatrician training.

As if there was not enough evidence that pediatric dermatologists are in high demand, SPD pediatric dermatology workforce surveys from the last 5 years, which will soon be updated, show similar indications.^7,10 Fogel and Teng¹¹ showed that 60% of surveyed pediatric dermatologists (N=226) were academic and 81% were salaried. Unlike previous data,¹ the investigators showed that children constituted 79.5% of respondents’ patient populations. The academic practice environment favored by the majority of pediatric dermatologists was associated with seeing fewer patients per week and longer wait times (approximately 60 days for a pediatric dermatologist vs 15 days in other practice environments).¹¹ Therefore, the demand continues to be unmet even in many institutions with pediatric dermatology practitioners in place.

For the medical student or resident seeking a career in pediatric dermatology, it appears that finding and working on projects with mentors likely is the key to stepping in the field. From my own experience, pediatric dermatologists are extremely friendly and open to supporting career development in earnest students. Reach out to potential mentors months before starting desired electives, as you are competing with other students and pediatrics, dermatology, and emergency medicine residents. Joining and attending meetings of the SPD is a great way to find direction in this friendly and collegial field. Additionally, pediatric dermatology sessions at the annual meetings of the American Academy of Dermatology are a wonderful way to experience the excitement of the field. As a pediatric dermatologist in practice for almost 2 decades, I can honestly say that the field is always intellectually stimulating and evolving rapidly through enhanced understanding of disease pathogenesis, genetics, and therapeutics. Helping children and their parents/guardians never gets boring.

The solution to improving the size and accessibility of the pediatric dermatology workforce is not simple and likely starts from the bottom up. More than 75% of pediatric dermatologists favor implementing systems to encourage medical students to pursue a career in pediatric dermatology.⁷ Increasing resident exposure to dedicated pediatric dermatology training time enhances satisfaction.⁵ Increased funding of fellowships can help these students and residents meet their goals. Current fellowship training programs now total 36, but not all approved institutions have been able to support a postgraduate year 5 (PGY-5) or higher fellow, and in my experience some institutions have avoided adding a fellow due to lack of funding internally. The average pediatric dermatologist earns $100,000 less than colleagues who treat adults, which is an impediment to the expansion of the field.¹⁰ This disparity may chase away practitioners, especially those with medical school debt. Debt forgiveness programs, enhanced practice development, and better base pay for pediatric dermatologists could positively impact growth in this specialty. Dermatology and pediatrics training programs need to dedicate more money and developmental support for pediatric dermatologists as a way to invest in the quality of pediatric dermatology education for their trainees. By recognizing the true value of the academic contributions of pediatric dermatologists, dermatology residency programs can invest in producing trainees with greater aplomb and acumen in pediatric dermatology.

The Society for Pediatric Dermatology (SPD) was established in 1975, and the pediatric dermatology workforce shortage began shortly after. In 1986, Honig and Burke¹ reported that opportunities in pediatric dermatology were limited and that pediatric dermatologists were predominantly located in larger teaching hospitals and selected private practice settings; furthermore, only approximately 20% had patient populations comprising more than 75% children.¹ Positive changes have occurred since that time, with more practitioners dedicated to pediatric dermatology and increased opportunities within the specialty. The SPD has expanded to a thriving group of collegial pediatric dermatologists now topping 1200 members worldwide.

Although the SPD has strongly influenced practice development in pediatric dermatology, there are fewer than 300 board-certified pediatric dermatologists in the United States and approximately double that number of pediatric dermatology practitioners. The deficiency is glaring based on the national population alone. The US Census Bureau reported 325,719,178 individuals living in the United States (as of July 1, 2017).² With approximately 75 million children in the United States and estimates that 22.8% of the population is younger than 18 years,³ there currently is 1 pediatric dermatologist for every 120,000 children or more.

As if the numbers alone were not adequate, a number of publications have addressed the benefits of pediatric dermatologists in both dermatology and pediatrics training and furthermore in pediatric care. A 2004 survey of dermatology program directors and chairpersons regarding the issue of the pediatric dermatology workforce shortage revealed that 45 of 94 (47.9%) programs employed a pediatric dermatologist and 24 (25.5%) had been looking to hire one for more than a year.⁴ Although more pediatric dermatologists have joined the workforce, it is not surprising that programs with no pediatric dermatologists want them. First, pediatric dermatologists dramatically improve the quality of training with regard to pediatric dermatology education and can increase dermatology residents’ comfort level with children. In a survey of a group of graduating third-year dermatology residents, dermatology residency program directors, and pediatric dermatology fellowship program directors by Nijhawan et al,⁵ residents who were trained in a program with one or more full-time pediatric dermatologists were more likely to feel competent treating children and to feel satisfied with their training program’s pediatric dermatology curriculum than residents without contact with a full-time pediatric dermatologist (50.0% vs 5.9% [P=.002] and 85.3% vs 52.9% [P<.001], respectively). The availability of a pediatric dermatology fellowship further enhanced satisfaction. Residents in programs with no full-time pediatric dermatologist on staff were more likely to be somewhat or extremely dissatisfied with their pediatric dermatology training. Residency program directors were more satisfied with their curriculums when there was one or more pediatric dermatologist on staff (P<.01).⁵

Programs with pediatric dermatologists also offer easy access to a mentor in the field. In a 2010 survey of pediatric dermatologists (published in 2014), Admani et al⁶ reported that 84% (91/109) of respondents (board-certified pediatric dermatologists) cited mentorship as the most important factor influencing their career choice. Exposure to the specialty was noted as a key motivating factor. In my opinion, the actual inclusion of a pediatric dermatology fellowship, whether the position is filled or not, appears to increase the chances of expansion and retention in the field. In the 2014 SPD workforce survey, more than 62% (61/98) of respondents were fellowship trained.⁷ In 2004 there were only 6 pediatric dermatology fellowship training programs. We have come quite far now with 36 fellowships as of August 12, 2018.⁸ The cost of education of course is not simple when pediatric dermatology fellowships are unfunded by the Accreditation Council for Graduate Medical Education; however, it is clear that the initial investment can create ongoing returns in pediatric dermatology.

Furthermore, due to the outpatient burden of skin disease in a pediatrics practice, providing pediatric trainees with contact with a pediatric dermatologist is needed. Prindaville et al⁹ performed a review from 2006 through 2010 of the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey databases, which revealed that 9% of 23 million pediatric visits during this time period were for dermatologic diseases; therefore, knowledge of pediatric dermatology is vital to pediatrician training.

As if there was not enough evidence that pediatric dermatologists are in high demand, SPD pediatric dermatology workforce surveys from the last 5 years, which will soon be updated, show similar indications.^7,10 Fogel and Teng¹¹ showed that 60% of surveyed pediatric dermatologists (N=226) were academic and 81% were salaried. Unlike previous data,¹ the investigators showed that children constituted 79.5% of respondents’ patient populations. The academic practice environment favored by the majority of pediatric dermatologists was associated with seeing fewer patients per week and longer wait times (approximately 60 days for a pediatric dermatologist vs 15 days in other practice environments).¹¹ Therefore, the demand continues to be unmet even in many institutions with pediatric dermatology practitioners in place.

For the medical student or resident seeking a career in pediatric dermatology, it appears that finding and working on projects with mentors likely is the key to stepping in the field. From my own experience, pediatric dermatologists are extremely friendly and open to supporting career development in earnest students. Reach out to potential mentors months before starting desired electives, as you are competing with other students and pediatrics, dermatology, and emergency medicine residents. Joining and attending meetings of the SPD is a great way to find direction in this friendly and collegial field. Additionally, pediatric dermatology sessions at the annual meetings of the American Academy of Dermatology are a wonderful way to experience the excitement of the field. As a pediatric dermatologist in practice for almost 2 decades, I can honestly say that the field is always intellectually stimulating and evolving rapidly through enhanced understanding of disease pathogenesis, genetics, and therapeutics. Helping children and their parents/guardians never gets boring.

The solution to improving the size and accessibility of the pediatric dermatology workforce is not simple and likely starts from the bottom up. More than 75% of pediatric dermatologists favor implementing systems to encourage medical students to pursue a career in pediatric dermatology.⁷ Increasing resident exposure to dedicated pediatric dermatology training time enhances satisfaction.⁵ Increased funding of fellowships can help these students and residents meet their goals. Current fellowship training programs now total 36, but not all approved institutions have been able to support a postgraduate year 5 (PGY-5) or higher fellow, and in my experience some institutions have avoided adding a fellow due to lack of funding internally. The average pediatric dermatologist earns $100,000 less than colleagues who treat adults, which is an impediment to the expansion of the field.¹⁰ This disparity may chase away practitioners, especially those with medical school debt. Debt forgiveness programs, enhanced practice development, and better base pay for pediatric dermatologists could positively impact growth in this specialty. Dermatology and pediatrics training programs need to dedicate more money and developmental support for pediatric dermatologists as a way to invest in the quality of pediatric dermatology education for their trainees. By recognizing the true value of the academic contributions of pediatric dermatologists, dermatology residency programs can invest in producing trainees with greater aplomb and acumen in pediatric dermatology.

The Diagnosis: Self-healing Langerhans Cell Histiocytosis

Histopathologic examination showed an infiltrate of mononuclear cells with indented nuclei admixed with a variable dermal inflammatory infiltrate. Immunohistochemistry demonstrated cells that were strongly positive for CD1a (Figure, A) and langerin (Figure, B) antigens as well as S-100 protein (Figure, C), which was consistent with Langerhans cell histiocytosis (LCH).

Histiocytoses are a heterogeneous group of disorders in which the infiltrating cells belong to the mononuclear phagocyte system.^1,2 Langerhans cell histiocytosis is the most common dendritic cell-related histiocytosis, occurring in approximately 5 per 1 million children annually, giving it an incidence comparable to pediatric Hodgkin lymphoma and acute myeloid leukemia.^1,2

Historically, there has been much debate about the pathogenesis of the disease.² Until recently it was unknown whether LCH was primarily a neoplastic or an inflammatory disorder. Although the condition initially was thought to have a reactive etiology,¹ more recent evidence suggests a clonal neoplastic process. Langerhans cell histiocytosis lesions are clonal and display malignancy-associated mechanisms such as immune evasion. Genome sequencing has revealed several mutations in precursor myeloid cells that result in the common downstream hyperactivation of the mitogen-activated protein kinase signaling pathway that regulates cell proliferation and differentiation.¹

Langerhans cell histiocytosis displays a wide spectrum of clinical phenotypes, which historically were subclassified as eosinophilic granulomas (localized lesions in bone), Hand-Schüller-Christian disease (multiple organ involvement with the classic triad of skull defects, diabetes insipidus, and exophthalmos), and Letterer-Siwe disease (visceral lesions involving multiple organs).³ However, in 1997 the Reclassification Working Group of the Histiocyte Society redefined LCH as single-system single site (SS-s) LCH, single-system multisite LCH, and multisystem LCH.⁴

In SS-s LCH, the most common site is bone (82%), followed by the skin (12%).⁵ Skin SS-s LCH classically presents as multiple skin lesions at birth without systemic manifestations; the lesions spontaneously involute within a few months.⁶ Less commonly, skin SS-s LCH can present as a single lesion. Berger et al⁷ described 4 neonates with unilesional skin SS-s LCH. Since then, more than 30 cases have been reported in the literature,⁸ and we report herein another unilesional self-healing LCH.

The morphology of skin lesions in self-healing LCH is highly variable, with the most common being multiple erythematous crusted papules (50%), followed by eczematous scaly lesions resembling seborrheic dermatitis in intertriginous areas (37.5%).^3,6 Unilesional self-healing LCH typically presents as an ulcerated or crusted nodule or papule on the trunk. This variability results in a large differential diagnosis. Self-healing LCH is easily mistaken for infectious processes including neonatal herpes simplex and varicella-zoster virus infection.⁹ Often, the dermatology department is consulted to rule out LCH when the asymptomatic neonate does not respond to parenteral acyclovir.

Less commonly, the magenta-colored papulonodules of self-healing LCH can mimic blueberry muffin rash and mandate a workup for intrauterine infections, especially cytomegalovirus, rubella, and blood dyscrasia.¹⁰ Other noninfectious processes in the differential of self-healing LCH include congenital infantile hemangioma, neonatal lupus erythematosus, seborrheic dermatitis (cradle cap), pyogenic granuloma, and psoriasis.^3,10 Definitive diagnosis requires histopathology.

Because unilesional self-healing LCH has an excellent prognosis and usually resolves on its own, therapy is unnecessary.^3,8 One large retrospective study (N=146) found that of all patients with skin lesions, 56% were managed with biopsy only.⁵ Other options include watchful waiting and topical corticosteroids. If the skin lesions are large, ulcerated, and/or painful, alkylating antitumor agents have been used. For extensive cutaneous disease, systemic corticosteroids combined with chemotherapy and psoralen plus UVA can be effective.⁶

The primary concern in the management of self-healing LCH is that the solitary skin lesion may be the harbinger of an aggressive disorder that can progress to systemic disease.⁵ Moreover, recurrent visceral or disseminated disease may occur months to years after resolution of solitary skin lesions.⁹ Studies have shown that localized and disseminated disease cannot be differentiated on the basis of clinical findings, histology, immunohistochemistry, or biomarkers.^3,11 As a result, an evaluation for systemic disease should be performed at the time of diagnosis for cutaneous LCH.^3,9 Minimum baseline studies recommended by the Writing Group of the Histiocyte Society include a complete blood cell count, liver function tests, coagulation studies, chest radiography, skeletal surveys, and urine osmolality testing.¹² Periodic clinical follow-up is recommended for all variants of LCH.⁹

Our case was diagnosed as self-healing LCH based on histologic findings. No treatment was required, and at 3-month follow-up the infant was asymptomatic without recurrence and was meeting all developmental milestones.

The Diagnosis: Self-healing Langerhans Cell Histiocytosis

Histopathologic examination showed an infiltrate of mononuclear cells with indented nuclei admixed with a variable dermal inflammatory infiltrate. Immunohistochemistry demonstrated cells that were strongly positive for CD1a (Figure, A) and langerin (Figure, B) antigens as well as S-100 protein (Figure, C), which was consistent with Langerhans cell histiocytosis (LCH).

Histiocytoses are a heterogeneous group of disorders in which the infiltrating cells belong to the mononuclear phagocyte system.^1,2 Langerhans cell histiocytosis is the most common dendritic cell-related histiocytosis, occurring in approximately 5 per 1 million children annually, giving it an incidence comparable to pediatric Hodgkin lymphoma and acute myeloid leukemia.^1,2

Historically, there has been much debate about the pathogenesis of the disease.² Until recently it was unknown whether LCH was primarily a neoplastic or an inflammatory disorder. Although the condition initially was thought to have a reactive etiology,¹ more recent evidence suggests a clonal neoplastic process. Langerhans cell histiocytosis lesions are clonal and display malignancy-associated mechanisms such as immune evasion. Genome sequencing has revealed several mutations in precursor myeloid cells that result in the common downstream hyperactivation of the mitogen-activated protein kinase signaling pathway that regulates cell proliferation and differentiation.¹

Langerhans cell histiocytosis displays a wide spectrum of clinical phenotypes, which historically were subclassified as eosinophilic granulomas (localized lesions in bone), Hand-Schüller-Christian disease (multiple organ involvement with the classic triad of skull defects, diabetes insipidus, and exophthalmos), and Letterer-Siwe disease (visceral lesions involving multiple organs).³ However, in 1997 the Reclassification Working Group of the Histiocyte Society redefined LCH as single-system single site (SS-s) LCH, single-system multisite LCH, and multisystem LCH.⁴

In SS-s LCH, the most common site is bone (82%), followed by the skin (12%).⁵ Skin SS-s LCH classically presents as multiple skin lesions at birth without systemic manifestations; the lesions spontaneously involute within a few months.⁶ Less commonly, skin SS-s LCH can present as a single lesion. Berger et al⁷ described 4 neonates with unilesional skin SS-s LCH. Since then, more than 30 cases have been reported in the literature,⁸ and we report herein another unilesional self-healing LCH.

The morphology of skin lesions in self-healing LCH is highly variable, with the most common being multiple erythematous crusted papules (50%), followed by eczematous scaly lesions resembling seborrheic dermatitis in intertriginous areas (37.5%).^3,6 Unilesional self-healing LCH typically presents as an ulcerated or crusted nodule or papule on the trunk. This variability results in a large differential diagnosis. Self-healing LCH is easily mistaken for infectious processes including neonatal herpes simplex and varicella-zoster virus infection.⁹ Often, the dermatology department is consulted to rule out LCH when the asymptomatic neonate does not respond to parenteral acyclovir.

Less commonly, the magenta-colored papulonodules of self-healing LCH can mimic blueberry muffin rash and mandate a workup for intrauterine infections, especially cytomegalovirus, rubella, and blood dyscrasia.¹⁰ Other noninfectious processes in the differential of self-healing LCH include congenital infantile hemangioma, neonatal lupus erythematosus, seborrheic dermatitis (cradle cap), pyogenic granuloma, and psoriasis.^3,10 Definitive diagnosis requires histopathology.

Because unilesional self-healing LCH has an excellent prognosis and usually resolves on its own, therapy is unnecessary.^3,8 One large retrospective study (N=146) found that of all patients with skin lesions, 56% were managed with biopsy only.⁵ Other options include watchful waiting and topical corticosteroids. If the skin lesions are large, ulcerated, and/or painful, alkylating antitumor agents have been used. For extensive cutaneous disease, systemic corticosteroids combined with chemotherapy and psoralen plus UVA can be effective.⁶

The primary concern in the management of self-healing LCH is that the solitary skin lesion may be the harbinger of an aggressive disorder that can progress to systemic disease.⁵ Moreover, recurrent visceral or disseminated disease may occur months to years after resolution of solitary skin lesions.⁹ Studies have shown that localized and disseminated disease cannot be differentiated on the basis of clinical findings, histology, immunohistochemistry, or biomarkers.^3,11 As a result, an evaluation for systemic disease should be performed at the time of diagnosis for cutaneous LCH.^3,9 Minimum baseline studies recommended by the Writing Group of the Histiocyte Society include a complete blood cell count, liver function tests, coagulation studies, chest radiography, skeletal surveys, and urine osmolality testing.¹² Periodic clinical follow-up is recommended for all variants of LCH.⁹

Our case was diagnosed as self-healing LCH based on histologic findings. No treatment was required, and at 3-month follow-up the infant was asymptomatic without recurrence and was meeting all developmental milestones.

The Diagnosis: Self-healing Langerhans Cell Histiocytosis

Histopathologic examination showed an infiltrate of mononuclear cells with indented nuclei admixed with a variable dermal inflammatory infiltrate. Immunohistochemistry demonstrated cells that were strongly positive for CD1a (Figure, A) and langerin (Figure, B) antigens as well as S-100 protein (Figure, C), which was consistent with Langerhans cell histiocytosis (LCH).

Histiocytoses are a heterogeneous group of disorders in which the infiltrating cells belong to the mononuclear phagocyte system.^1,2 Langerhans cell histiocytosis is the most common dendritic cell-related histiocytosis, occurring in approximately 5 per 1 million children annually, giving it an incidence comparable to pediatric Hodgkin lymphoma and acute myeloid leukemia.^1,2

Historically, there has been much debate about the pathogenesis of the disease.² Until recently it was unknown whether LCH was primarily a neoplastic or an inflammatory disorder. Although the condition initially was thought to have a reactive etiology,¹ more recent evidence suggests a clonal neoplastic process. Langerhans cell histiocytosis lesions are clonal and display malignancy-associated mechanisms such as immune evasion. Genome sequencing has revealed several mutations in precursor myeloid cells that result in the common downstream hyperactivation of the mitogen-activated protein kinase signaling pathway that regulates cell proliferation and differentiation.¹

Langerhans cell histiocytosis displays a wide spectrum of clinical phenotypes, which historically were subclassified as eosinophilic granulomas (localized lesions in bone), Hand-Schüller-Christian disease (multiple organ involvement with the classic triad of skull defects, diabetes insipidus, and exophthalmos), and Letterer-Siwe disease (visceral lesions involving multiple organs).³ However, in 1997 the Reclassification Working Group of the Histiocyte Society redefined LCH as single-system single site (SS-s) LCH, single-system multisite LCH, and multisystem LCH.⁴

In SS-s LCH, the most common site is bone (82%), followed by the skin (12%).⁵ Skin SS-s LCH classically presents as multiple skin lesions at birth without systemic manifestations; the lesions spontaneously involute within a few months.⁶ Less commonly, skin SS-s LCH can present as a single lesion. Berger et al⁷ described 4 neonates with unilesional skin SS-s LCH. Since then, more than 30 cases have been reported in the literature,⁸ and we report herein another unilesional self-healing LCH.

The morphology of skin lesions in self-healing LCH is highly variable, with the most common being multiple erythematous crusted papules (50%), followed by eczematous scaly lesions resembling seborrheic dermatitis in intertriginous areas (37.5%).^3,6 Unilesional self-healing LCH typically presents as an ulcerated or crusted nodule or papule on the trunk. This variability results in a large differential diagnosis. Self-healing LCH is easily mistaken for infectious processes including neonatal herpes simplex and varicella-zoster virus infection.⁹ Often, the dermatology department is consulted to rule out LCH when the asymptomatic neonate does not respond to parenteral acyclovir.

Less commonly, the magenta-colored papulonodules of self-healing LCH can mimic blueberry muffin rash and mandate a workup for intrauterine infections, especially cytomegalovirus, rubella, and blood dyscrasia.¹⁰ Other noninfectious processes in the differential of self-healing LCH include congenital infantile hemangioma, neonatal lupus erythematosus, seborrheic dermatitis (cradle cap), pyogenic granuloma, and psoriasis.^3,10 Definitive diagnosis requires histopathology.

Because unilesional self-healing LCH has an excellent prognosis and usually resolves on its own, therapy is unnecessary.^3,8 One large retrospective study (N=146) found that of all patients with skin lesions, 56% were managed with biopsy only.⁵ Other options include watchful waiting and topical corticosteroids. If the skin lesions are large, ulcerated, and/or painful, alkylating antitumor agents have been used. For extensive cutaneous disease, systemic corticosteroids combined with chemotherapy and psoralen plus UVA can be effective.⁶

The primary concern in the management of self-healing LCH is that the solitary skin lesion may be the harbinger of an aggressive disorder that can progress to systemic disease.⁵ Moreover, recurrent visceral or disseminated disease may occur months to years after resolution of solitary skin lesions.⁹ Studies have shown that localized and disseminated disease cannot be differentiated on the basis of clinical findings, histology, immunohistochemistry, or biomarkers.^3,11 As a result, an evaluation for systemic disease should be performed at the time of diagnosis for cutaneous LCH.^3,9 Minimum baseline studies recommended by the Writing Group of the Histiocyte Society include a complete blood cell count, liver function tests, coagulation studies, chest radiography, skeletal surveys, and urine osmolality testing.¹² Periodic clinical follow-up is recommended for all variants of LCH.⁹

Our case was diagnosed as self-healing LCH based on histologic findings. No treatment was required, and at 3-month follow-up the infant was asymptomatic without recurrence and was meeting all developmental milestones.

Symptoms of gastrointestinal involvement such as abdominal pain and vomiting may delay diagnosis of Kawasaki disease in pediatric patients.

NaiyanaDonraman/Thinkstock

“The clinical onset of Kawasaki disease with gastrointestinal involvement often leads to diagnostic and therapeutic delays – a risk factor for the development of coronary complications,” Claudia Colomba, MD, from the department of sciences for health promotion and mother and child care at the University of Palermo (Italy), and her colleagues wrote in the Journal of Pediatrics.

After caring for a boy aged 14 years at their center who presented with these symptoms, Dr. Colomba and her colleagues performed a search of the PubMed and Scopus databases and identified 33 articles with 48 total cases of Kawasaki disease with intestinal involvement between 1979 and 2017.

There were 40 cases of fever (82%), 34 cases of abdominal pain (69%), and 24 cases of vomiting (49%) at disease onset, with diarrhea occurring in 14 cases (29%) and jaundice in 1 case (2%), the researchers noted. Cardiac involvement occurred in 21 cases (43%). With regard to imaging, 38 cases of pseudo-obstruction (77%) were identified by plain radiograph, ultrasonography, and CT. Over half of the cases required surgery; of these 25 cases (51%), 8 cases involved a resection of the restricted loop and included a temporary colostomy (16%), 5 cases were exploratory laparotomy (10%), and there was 1 case with enterolysis (2%).

A total of 45 patients received medical treatment, with 12 patients (25%) receiving intravenous immunoglobulin and 18 (37%) receiving intravenous immunoglobulin plus aspirin. One patient had cyanosis and hand and foot gangrene. There were three patients who died, with massive liver necrosis identified during the autopsy of one patient. Of the other two who died, one did so 2 days after exploratory laparotomy and the other died because of Pseudomonas septic shock.

The researchers reported a good outcome in 28 patients (57%), which included 3 cases where there was no treatment.

“The diagnosis of Kawasaki disease should be considered in all children with fever, abdominal pain, and radiologic signs of pseudo-obstruction, even in the absence of typical symptoms and signs,” Dr. Colomba and her colleagues wrote. “A more comprehensive analysis including all clinical forms of Kawasaki disease would be useful to correlate intestinal involvement with worse outcomes for cardiac complications, as well as to clues to more rapid diagnosis and avoidance of unnecessary invasive procedures.”

The authors reported no relevant conflicts of interest.

SOURCE: Colomba C et al. J Pediatr. 2018 Jul 17. doi: 10.1016/j.jpeds.2018.06.034.

Symptoms of gastrointestinal involvement such as abdominal pain and vomiting may delay diagnosis of Kawasaki disease in pediatric patients.

NaiyanaDonraman/Thinkstock

“The clinical onset of Kawasaki disease with gastrointestinal involvement often leads to diagnostic and therapeutic delays – a risk factor for the development of coronary complications,” Claudia Colomba, MD, from the department of sciences for health promotion and mother and child care at the University of Palermo (Italy), and her colleagues wrote in the Journal of Pediatrics.

After caring for a boy aged 14 years at their center who presented with these symptoms, Dr. Colomba and her colleagues performed a search of the PubMed and Scopus databases and identified 33 articles with 48 total cases of Kawasaki disease with intestinal involvement between 1979 and 2017.

There were 40 cases of fever (82%), 34 cases of abdominal pain (69%), and 24 cases of vomiting (49%) at disease onset, with diarrhea occurring in 14 cases (29%) and jaundice in 1 case (2%), the researchers noted. Cardiac involvement occurred in 21 cases (43%). With regard to imaging, 38 cases of pseudo-obstruction (77%) were identified by plain radiograph, ultrasonography, and CT. Over half of the cases required surgery; of these 25 cases (51%), 8 cases involved a resection of the restricted loop and included a temporary colostomy (16%), 5 cases were exploratory laparotomy (10%), and there was 1 case with enterolysis (2%).

A total of 45 patients received medical treatment, with 12 patients (25%) receiving intravenous immunoglobulin and 18 (37%) receiving intravenous immunoglobulin plus aspirin. One patient had cyanosis and hand and foot gangrene. There were three patients who died, with massive liver necrosis identified during the autopsy of one patient. Of the other two who died, one did so 2 days after exploratory laparotomy and the other died because of Pseudomonas septic shock.

The researchers reported a good outcome in 28 patients (57%), which included 3 cases where there was no treatment.

“The diagnosis of Kawasaki disease should be considered in all children with fever, abdominal pain, and radiologic signs of pseudo-obstruction, even in the absence of typical symptoms and signs,” Dr. Colomba and her colleagues wrote. “A more comprehensive analysis including all clinical forms of Kawasaki disease would be useful to correlate intestinal involvement with worse outcomes for cardiac complications, as well as to clues to more rapid diagnosis and avoidance of unnecessary invasive procedures.”

The authors reported no relevant conflicts of interest.

SOURCE: Colomba C et al. J Pediatr. 2018 Jul 17. doi: 10.1016/j.jpeds.2018.06.034.

Symptoms of gastrointestinal involvement such as abdominal pain and vomiting may delay diagnosis of Kawasaki disease in pediatric patients.

NaiyanaDonraman/Thinkstock

“The clinical onset of Kawasaki disease with gastrointestinal involvement often leads to diagnostic and therapeutic delays – a risk factor for the development of coronary complications,” Claudia Colomba, MD, from the department of sciences for health promotion and mother and child care at the University of Palermo (Italy), and her colleagues wrote in the Journal of Pediatrics.

After caring for a boy aged 14 years at their center who presented with these symptoms, Dr. Colomba and her colleagues performed a search of the PubMed and Scopus databases and identified 33 articles with 48 total cases of Kawasaki disease with intestinal involvement between 1979 and 2017.

There were 40 cases of fever (82%), 34 cases of abdominal pain (69%), and 24 cases of vomiting (49%) at disease onset, with diarrhea occurring in 14 cases (29%) and jaundice in 1 case (2%), the researchers noted. Cardiac involvement occurred in 21 cases (43%). With regard to imaging, 38 cases of pseudo-obstruction (77%) were identified by plain radiograph, ultrasonography, and CT. Over half of the cases required surgery; of these 25 cases (51%), 8 cases involved a resection of the restricted loop and included a temporary colostomy (16%), 5 cases were exploratory laparotomy (10%), and there was 1 case with enterolysis (2%).

A total of 45 patients received medical treatment, with 12 patients (25%) receiving intravenous immunoglobulin and 18 (37%) receiving intravenous immunoglobulin plus aspirin. One patient had cyanosis and hand and foot gangrene. There were three patients who died, with massive liver necrosis identified during the autopsy of one patient. Of the other two who died, one did so 2 days after exploratory laparotomy and the other died because of Pseudomonas septic shock.

The researchers reported a good outcome in 28 patients (57%), which included 3 cases where there was no treatment.

“The diagnosis of Kawasaki disease should be considered in all children with fever, abdominal pain, and radiologic signs of pseudo-obstruction, even in the absence of typical symptoms and signs,” Dr. Colomba and her colleagues wrote. “A more comprehensive analysis including all clinical forms of Kawasaki disease would be useful to correlate intestinal involvement with worse outcomes for cardiac complications, as well as to clues to more rapid diagnosis and avoidance of unnecessary invasive procedures.”

The authors reported no relevant conflicts of interest.

SOURCE: Colomba C et al. J Pediatr. 2018 Jul 17. doi: 10.1016/j.jpeds.2018.06.034.

Although there have been significant improvements in patient outcomes for some forms of pediatric cancer, progress has been painfully slow for others. An increasing understanding of pediatric cancers is highlighting the unique molecular drivers and challenging the assumption that drugs developed in adults can be applied to children and young adults. Here, we discuss game-changing therapeutic advances and a shifting view of childhood cancers.

Unique genomic background

Although pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, they are the second leading cause of death in children aged 1 to 14 years. There are many different histological tumor types under the umbrella of childhood cancers, of which the most common are leukemias, central nervous system tumors, and lymphomas (Figure 1).^1,2

A ‘magic bullet’?

Chromosomal rearrangements are common in pediatric cancers. This type of molecular abnormality can result in a fusion of 2 different genes when the chromosome breaks apart and the pieces join back together in a muddled order. If the genetic code fuses in a manner that is “readable” by the cell, then it can drive aberrant activation of one or both genes.⁷ Gene fusions often involve kinase enzymes that are essential players in cell signaling pathways regulating hallmark cancer processes, such as unchecked cell proliferation. The fusion drives the constitutive activation of the kinase and, thus, these downstream signaling pathways.

One of the first chromosomal rearrangements linked to cancer, BCR-ABL1 – more commonly known as the Philadelphia chromosome – results in aberrant activation of the ABL1 kinase. It is present in nearly all cases of chronic myeloid leukemia (CML) and 3% to 5% of patients with ALL, and thus became the central focus of targeted drug development. Imatinib was initially approved by the US Food and Drug Administration (FDA) in 2001 for the treatment of adult patients with CML and had such a significant impact on the treatment landscape that it made the cover of Time magazine as a “magic bullet” in the war on cancer.⁸

Approval was expanded into pediatric patients in 2006 and for pediatric patients with ALL in 2013. However, as with the use of most kinase inhibitors, tumors can evolve under the selective pressure of treatment, developing additional molecular abnormalities that drive resistance.⁹

Next-generation multikinase inhibitors that more potently inhibit the BCR-ABL1 fusion protein have been developed to provide additional treatment options for patients who become resistant to imatinib. Dasatinib and nilotinib are among several drugs that have recently been approved for pediatric cancer therapy (Table 1). Both therapies were approved to treat children with Philadelphia chromosome-positive CML in the chronic phase in either the front- or second-line setting after failure of imatinib.

Other prominent gene fusions

Gene fusions involving the anaplastic lymphoma kinase (ALK) occur in patients with non–small-cell lung cancer and ALK inhibitors have provided an effective new treatment option for patients whose tumors display this abnormality.

ALK fusions are also a prominent feature of several kinds of pediatric cancers and ALK inhibitors offer promise in this setting.^7,12 An NPM-ALK fusion is found in 90% of pediatric anaplastic large cell lymphoma (ALCL) cases,¹³ whereas a variety of ALK fusions are found in up to half of patients with inflammatory myofibroblastic tumor (IMT), a rare form of soft tissue sarcoma.¹⁴ ALK inhibitors are being tested in a variety of clinical trials in pediatric patients (Table 2).

CAR T cells transformative in ALL

A variety of different types of immunotherapy have been tested in patients with pediatric cancers. In general, immunotherapy has proved less effective than in adult cancers, possibly because of the lower tumor mutation burden in pediatric cancers, which means there are likely fewer cancer antigens to provoke an anti-tumor immune response.

There are notable exceptions among the disappointments, however, and most exciting is the development of chimeric antigen receptor (CAR) T cells. CAR T cells fall into a category of immunotherapy known as adoptive cell therapy (ACT), in which immune cells are harvested from a patient and grown outside the body to increase their numbers before being reinfused into the patient.

In the case of CAR T-cell therapy, the cells are genetically engineered to express a CAR that endows them with tumor-targeting capabilities. To date, the development of CAR T cells has focused on the use of the CD19 antigen as a target, which is highly expressed on a variety of B-cell malignancies, including several of the most common forms of pediatric cancer. ASCO shined the spotlight on CAR T-cell therapy this year, naming it the Advance of the Year for 2018, saying that the treatment is “poised to transform childhood ALL.”¹⁹

Two CD19-targeted CAR T-cell therapies – tisagenlecleucel and axicabtagene ciloleucel – were brought to market in 2017. Only tisagenlecleucel is approved in the pediatric ALL population, however, having been awarded approval for the treatment of patients aged up to 25 years whose disease is refractory to or relapsed after receiving at least 2 prior therapies. In the pivotal trial, complete responses were observed in more than 60% of patients.²⁰ Clinical trials of both CAR T-cell therapies in pediatric ALL and non-Hodgkin lymphoma are ongoing (Table 3).

More immunotherapy approvals

The immune checkpoint inhibitors, which work by blocking inhibitory receptors on the surface of T cells, have also had recent approvals in pediatric patient populations. Pembrolizumab and nivolumab, inhibitors of the programmed cell death receptor 1 (PD-1) protein, have both been approved for use in adult and pediatric patients (older than 12 years) with relapsed/refractory metastatic colorectal cancer (and other solid tumors in the case of pembrolizumab) that display defects in the mismatch repair pathway that fixes damaged DNA or in patients that have high levels of microsatellite instability. Both deficient mismatch repair and microsatellite instability–high can indicate a high mutation burden in a tumor, which may predict increased sensitivity to immunotherapy.²⁹

The approval in pediatric patients in both of those instances, however, was not based on data in pediatric patient populations but extrapolated from adult patients. Pembrolizumab is also approved for the treatment of adults and pediatric patients with classical Hodgkin lymphoma (cHL) after 3 or more previous treatments, but once again efficacy in the pediatric population was inferred from clinical trials performed in adults. Most recently, pembrolizumab was approved for the treatment of adult and pediatric patients with relapsed or refractory primary mediastinal large B-cell lymphoma.³⁰Ipilimumab, which targets a different T cell receptor – cytotoxic T lymphocyte antigen-4 (CTLA-4) – has been approved for the treatment of pediatric patients aged 12 years and older with metastatic melanoma. This expanded indication, following on from its approval in adult patients in 2011, was based on data from 2 trials in which objective responses were observed in 2 out of 17 patients, including 1 partial response that lasted 16 months.³¹Finally, antibody-drug conjugates (ADC), in which tumor antigen-targeting monoclonal antibodies are conjugated to cytotoxic payloads to combine the specificity of an antibody with the cell-killing potency of chemotherapy, have also generated some recent successes in pediatric cancers.

Gemtuzumab ozogamicin is an ADC that targets the CD33 protein, which is highly expressed on 85%-90% of cases of acute myeloid leukemia (AML). In 2000, it was the first ADC to be brought to market in the United States, but it was subsequently voluntarily withdrawn by the manufacturer in 2010 after confirmatory trials failed to show a survival benefit.

Recently, a meta-analysis of gemtuzumab ozogamicin trials suggested that the drug likely does improve long-term overall survival (OS) and reduce the risk of relapse and researchers developed an intermittent dosing schedule to help mitigate toxicity.³² This new dosing regimen received FDA approval in 2017 for the treatment of pediatric patients aged 2 years and older on the basis of 2 clinical trials.

In the MyloFrance-1 trial, 57 patients were administered 3 mg/m² gemtuzumab ozogamicin on days 1, 4, and 7 followed by cytarabine consolidation therapy and demonstrated a 26% CR rate and median recurrence-free survival of 11.6 months. In the phase 3 AML-19 trial, 237 patients received gemtuzumab ozogamicin at a dose of 6 mg/m² on day 1 and 3 mg/m² on day 8 or best supportive care. Gemtuzumab ozogamicin improved OS from 3.6 to 4.9 months.^33,34

Inotuzumab ozogamicin is a CD22-targeting ADC that has been FDA approved for the treatment of adult patients with relapsed/refractory B-cell precursor ALL since last year. The therapy has been available to pediatric patients through a compassionate access program, but it has not been extensively evaluated in this population. The results of a retrospective analysis of pediatric patients who received at least 1 dose of inotuzumab ozogamicin were presented at ASCO in 2017. Among 29 patients with heavily pretreated disease the CR rate was 62%, 72% of whom achieved MRD negativity.³⁵

Although there have been significant improvements in patient outcomes for some forms of pediatric cancer, progress has been painfully slow for others. An increasing understanding of pediatric cancers is highlighting the unique molecular drivers and challenging the assumption that drugs developed in adults can be applied to children and young adults. Here, we discuss game-changing therapeutic advances and a shifting view of childhood cancers.

Unique genomic background

Although pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, they are the second leading cause of death in children aged 1 to 14 years. There are many different histological tumor types under the umbrella of childhood cancers, of which the most common are leukemias, central nervous system tumors, and lymphomas (Figure 1).^1,2

A ‘magic bullet’?

Chromosomal rearrangements are common in pediatric cancers. This type of molecular abnormality can result in a fusion of 2 different genes when the chromosome breaks apart and the pieces join back together in a muddled order. If the genetic code fuses in a manner that is “readable” by the cell, then it can drive aberrant activation of one or both genes.⁷ Gene fusions often involve kinase enzymes that are essential players in cell signaling pathways regulating hallmark cancer processes, such as unchecked cell proliferation. The fusion drives the constitutive activation of the kinase and, thus, these downstream signaling pathways.

One of the first chromosomal rearrangements linked to cancer, BCR-ABL1 – more commonly known as the Philadelphia chromosome – results in aberrant activation of the ABL1 kinase. It is present in nearly all cases of chronic myeloid leukemia (CML) and 3% to 5% of patients with ALL, and thus became the central focus of targeted drug development. Imatinib was initially approved by the US Food and Drug Administration (FDA) in 2001 for the treatment of adult patients with CML and had such a significant impact on the treatment landscape that it made the cover of Time magazine as a “magic bullet” in the war on cancer.⁸

Approval was expanded into pediatric patients in 2006 and for pediatric patients with ALL in 2013. However, as with the use of most kinase inhibitors, tumors can evolve under the selective pressure of treatment, developing additional molecular abnormalities that drive resistance.⁹

Next-generation multikinase inhibitors that more potently inhibit the BCR-ABL1 fusion protein have been developed to provide additional treatment options for patients who become resistant to imatinib. Dasatinib and nilotinib are among several drugs that have recently been approved for pediatric cancer therapy (Table 1). Both therapies were approved to treat children with Philadelphia chromosome-positive CML in the chronic phase in either the front- or second-line setting after failure of imatinib.

Other prominent gene fusions

Gene fusions involving the anaplastic lymphoma kinase (ALK) occur in patients with non–small-cell lung cancer and ALK inhibitors have provided an effective new treatment option for patients whose tumors display this abnormality.

ALK fusions are also a prominent feature of several kinds of pediatric cancers and ALK inhibitors offer promise in this setting.^7,12 An NPM-ALK fusion is found in 90% of pediatric anaplastic large cell lymphoma (ALCL) cases,¹³ whereas a variety of ALK fusions are found in up to half of patients with inflammatory myofibroblastic tumor (IMT), a rare form of soft tissue sarcoma.¹⁴ ALK inhibitors are being tested in a variety of clinical trials in pediatric patients (Table 2).

CAR T cells transformative in ALL

A variety of different types of immunotherapy have been tested in patients with pediatric cancers. In general, immunotherapy has proved less effective than in adult cancers, possibly because of the lower tumor mutation burden in pediatric cancers, which means there are likely fewer cancer antigens to provoke an anti-tumor immune response.

There are notable exceptions among the disappointments, however, and most exciting is the development of chimeric antigen receptor (CAR) T cells. CAR T cells fall into a category of immunotherapy known as adoptive cell therapy (ACT), in which immune cells are harvested from a patient and grown outside the body to increase their numbers before being reinfused into the patient.

In the case of CAR T-cell therapy, the cells are genetically engineered to express a CAR that endows them with tumor-targeting capabilities. To date, the development of CAR T cells has focused on the use of the CD19 antigen as a target, which is highly expressed on a variety of B-cell malignancies, including several of the most common forms of pediatric cancer. ASCO shined the spotlight on CAR T-cell therapy this year, naming it the Advance of the Year for 2018, saying that the treatment is “poised to transform childhood ALL.”¹⁹

Two CD19-targeted CAR T-cell therapies – tisagenlecleucel and axicabtagene ciloleucel – were brought to market in 2017. Only tisagenlecleucel is approved in the pediatric ALL population, however, having been awarded approval for the treatment of patients aged up to 25 years whose disease is refractory to or relapsed after receiving at least 2 prior therapies. In the pivotal trial, complete responses were observed in more than 60% of patients.²⁰ Clinical trials of both CAR T-cell therapies in pediatric ALL and non-Hodgkin lymphoma are ongoing (Table 3).

More immunotherapy approvals

The immune checkpoint inhibitors, which work by blocking inhibitory receptors on the surface of T cells, have also had recent approvals in pediatric patient populations. Pembrolizumab and nivolumab, inhibitors of the programmed cell death receptor 1 (PD-1) protein, have both been approved for use in adult and pediatric patients (older than 12 years) with relapsed/refractory metastatic colorectal cancer (and other solid tumors in the case of pembrolizumab) that display defects in the mismatch repair pathway that fixes damaged DNA or in patients that have high levels of microsatellite instability. Both deficient mismatch repair and microsatellite instability–high can indicate a high mutation burden in a tumor, which may predict increased sensitivity to immunotherapy.²⁹

The approval in pediatric patients in both of those instances, however, was not based on data in pediatric patient populations but extrapolated from adult patients. Pembrolizumab is also approved for the treatment of adults and pediatric patients with classical Hodgkin lymphoma (cHL) after 3 or more previous treatments, but once again efficacy in the pediatric population was inferred from clinical trials performed in adults. Most recently, pembrolizumab was approved for the treatment of adult and pediatric patients with relapsed or refractory primary mediastinal large B-cell lymphoma.³⁰Ipilimumab, which targets a different T cell receptor – cytotoxic T lymphocyte antigen-4 (CTLA-4) – has been approved for the treatment of pediatric patients aged 12 years and older with metastatic melanoma. This expanded indication, following on from its approval in adult patients in 2011, was based on data from 2 trials in which objective responses were observed in 2 out of 17 patients, including 1 partial response that lasted 16 months.³¹Finally, antibody-drug conjugates (ADC), in which tumor antigen-targeting monoclonal antibodies are conjugated to cytotoxic payloads to combine the specificity of an antibody with the cell-killing potency of chemotherapy, have also generated some recent successes in pediatric cancers.

Gemtuzumab ozogamicin is an ADC that targets the CD33 protein, which is highly expressed on 85%-90% of cases of acute myeloid leukemia (AML). In 2000, it was the first ADC to be brought to market in the United States, but it was subsequently voluntarily withdrawn by the manufacturer in 2010 after confirmatory trials failed to show a survival benefit.

Recently, a meta-analysis of gemtuzumab ozogamicin trials suggested that the drug likely does improve long-term overall survival (OS) and reduce the risk of relapse and researchers developed an intermittent dosing schedule to help mitigate toxicity.³² This new dosing regimen received FDA approval in 2017 for the treatment of pediatric patients aged 2 years and older on the basis of 2 clinical trials.

In the MyloFrance-1 trial, 57 patients were administered 3 mg/m² gemtuzumab ozogamicin on days 1, 4, and 7 followed by cytarabine consolidation therapy and demonstrated a 26% CR rate and median recurrence-free survival of 11.6 months. In the phase 3 AML-19 trial, 237 patients received gemtuzumab ozogamicin at a dose of 6 mg/m² on day 1 and 3 mg/m² on day 8 or best supportive care. Gemtuzumab ozogamicin improved OS from 3.6 to 4.9 months.^33,34

Inotuzumab ozogamicin is a CD22-targeting ADC that has been FDA approved for the treatment of adult patients with relapsed/refractory B-cell precursor ALL since last year. The therapy has been available to pediatric patients through a compassionate access program, but it has not been extensively evaluated in this population. The results of a retrospective analysis of pediatric patients who received at least 1 dose of inotuzumab ozogamicin were presented at ASCO in 2017. Among 29 patients with heavily pretreated disease the CR rate was 62%, 72% of whom achieved MRD negativity.³⁵

Although there have been significant improvements in patient outcomes for some forms of pediatric cancer, progress has been painfully slow for others. An increasing understanding of pediatric cancers is highlighting the unique molecular drivers and challenging the assumption that drugs developed in adults can be applied to children and young adults. Here, we discuss game-changing therapeutic advances and a shifting view of childhood cancers.

Unique genomic background

Although pediatric cancers are rare, representing just 1% of all new cancers diagnosed annually in the United States, they are the second leading cause of death in children aged 1 to 14 years. There are many different histological tumor types under the umbrella of childhood cancers, of which the most common are leukemias, central nervous system tumors, and lymphomas (Figure 1).^1,2

A ‘magic bullet’?

Chromosomal rearrangements are common in pediatric cancers. This type of molecular abnormality can result in a fusion of 2 different genes when the chromosome breaks apart and the pieces join back together in a muddled order. If the genetic code fuses in a manner that is “readable” by the cell, then it can drive aberrant activation of one or both genes.⁷ Gene fusions often involve kinase enzymes that are essential players in cell signaling pathways regulating hallmark cancer processes, such as unchecked cell proliferation. The fusion drives the constitutive activation of the kinase and, thus, these downstream signaling pathways.

One of the first chromosomal rearrangements linked to cancer, BCR-ABL1 – more commonly known as the Philadelphia chromosome – results in aberrant activation of the ABL1 kinase. It is present in nearly all cases of chronic myeloid leukemia (CML) and 3% to 5% of patients with ALL, and thus became the central focus of targeted drug development. Imatinib was initially approved by the US Food and Drug Administration (FDA) in 2001 for the treatment of adult patients with CML and had such a significant impact on the treatment landscape that it made the cover of Time magazine as a “magic bullet” in the war on cancer.⁸

Approval was expanded into pediatric patients in 2006 and for pediatric patients with ALL in 2013. However, as with the use of most kinase inhibitors, tumors can evolve under the selective pressure of treatment, developing additional molecular abnormalities that drive resistance.⁹

Next-generation multikinase inhibitors that more potently inhibit the BCR-ABL1 fusion protein have been developed to provide additional treatment options for patients who become resistant to imatinib. Dasatinib and nilotinib are among several drugs that have recently been approved for pediatric cancer therapy (Table 1). Both therapies were approved to treat children with Philadelphia chromosome-positive CML in the chronic phase in either the front- or second-line setting after failure of imatinib.

Other prominent gene fusions

Gene fusions involving the anaplastic lymphoma kinase (ALK) occur in patients with non–small-cell lung cancer and ALK inhibitors have provided an effective new treatment option for patients whose tumors display this abnormality.

ALK fusions are also a prominent feature of several kinds of pediatric cancers and ALK inhibitors offer promise in this setting.^7,12 An NPM-ALK fusion is found in 90% of pediatric anaplastic large cell lymphoma (ALCL) cases,¹³ whereas a variety of ALK fusions are found in up to half of patients with inflammatory myofibroblastic tumor (IMT), a rare form of soft tissue sarcoma.¹⁴ ALK inhibitors are being tested in a variety of clinical trials in pediatric patients (Table 2).

CAR T cells transformative in ALL

A variety of different types of immunotherapy have been tested in patients with pediatric cancers. In general, immunotherapy has proved less effective than in adult cancers, possibly because of the lower tumor mutation burden in pediatric cancers, which means there are likely fewer cancer antigens to provoke an anti-tumor immune response.

There are notable exceptions among the disappointments, however, and most exciting is the development of chimeric antigen receptor (CAR) T cells. CAR T cells fall into a category of immunotherapy known as adoptive cell therapy (ACT), in which immune cells are harvested from a patient and grown outside the body to increase their numbers before being reinfused into the patient.

In the case of CAR T-cell therapy, the cells are genetically engineered to express a CAR that endows them with tumor-targeting capabilities. To date, the development of CAR T cells has focused on the use of the CD19 antigen as a target, which is highly expressed on a variety of B-cell malignancies, including several of the most common forms of pediatric cancer. ASCO shined the spotlight on CAR T-cell therapy this year, naming it the Advance of the Year for 2018, saying that the treatment is “poised to transform childhood ALL.”¹⁹

Two CD19-targeted CAR T-cell therapies – tisagenlecleucel and axicabtagene ciloleucel – were brought to market in 2017. Only tisagenlecleucel is approved in the pediatric ALL population, however, having been awarded approval for the treatment of patients aged up to 25 years whose disease is refractory to or relapsed after receiving at least 2 prior therapies. In the pivotal trial, complete responses were observed in more than 60% of patients.²⁰ Clinical trials of both CAR T-cell therapies in pediatric ALL and non-Hodgkin lymphoma are ongoing (Table 3).

More immunotherapy approvals

The immune checkpoint inhibitors, which work by blocking inhibitory receptors on the surface of T cells, have also had recent approvals in pediatric patient populations. Pembrolizumab and nivolumab, inhibitors of the programmed cell death receptor 1 (PD-1) protein, have both been approved for use in adult and pediatric patients (older than 12 years) with relapsed/refractory metastatic colorectal cancer (and other solid tumors in the case of pembrolizumab) that display defects in the mismatch repair pathway that fixes damaged DNA or in patients that have high levels of microsatellite instability. Both deficient mismatch repair and microsatellite instability–high can indicate a high mutation burden in a tumor, which may predict increased sensitivity to immunotherapy.²⁹

The approval in pediatric patients in both of those instances, however, was not based on data in pediatric patient populations but extrapolated from adult patients. Pembrolizumab is also approved for the treatment of adults and pediatric patients with classical Hodgkin lymphoma (cHL) after 3 or more previous treatments, but once again efficacy in the pediatric population was inferred from clinical trials performed in adults. Most recently, pembrolizumab was approved for the treatment of adult and pediatric patients with relapsed or refractory primary mediastinal large B-cell lymphoma.³⁰Ipilimumab, which targets a different T cell receptor – cytotoxic T lymphocyte antigen-4 (CTLA-4) – has been approved for the treatment of pediatric patients aged 12 years and older with metastatic melanoma. This expanded indication, following on from its approval in adult patients in 2011, was based on data from 2 trials in which objective responses were observed in 2 out of 17 patients, including 1 partial response that lasted 16 months.³¹Finally, antibody-drug conjugates (ADC), in which tumor antigen-targeting monoclonal antibodies are conjugated to cytotoxic payloads to combine the specificity of an antibody with the cell-killing potency of chemotherapy, have also generated some recent successes in pediatric cancers.

Gemtuzumab ozogamicin is an ADC that targets the CD33 protein, which is highly expressed on 85%-90% of cases of acute myeloid leukemia (AML). In 2000, it was the first ADC to be brought to market in the United States, but it was subsequently voluntarily withdrawn by the manufacturer in 2010 after confirmatory trials failed to show a survival benefit.

Recently, a meta-analysis of gemtuzumab ozogamicin trials suggested that the drug likely does improve long-term overall survival (OS) and reduce the risk of relapse and researchers developed an intermittent dosing schedule to help mitigate toxicity.³² This new dosing regimen received FDA approval in 2017 for the treatment of pediatric patients aged 2 years and older on the basis of 2 clinical trials.

In the MyloFrance-1 trial, 57 patients were administered 3 mg/m² gemtuzumab ozogamicin on days 1, 4, and 7 followed by cytarabine consolidation therapy and demonstrated a 26% CR rate and median recurrence-free survival of 11.6 months. In the phase 3 AML-19 trial, 237 patients received gemtuzumab ozogamicin at a dose of 6 mg/m² on day 1 and 3 mg/m² on day 8 or best supportive care. Gemtuzumab ozogamicin improved OS from 3.6 to 4.9 months.^33,34

Inotuzumab ozogamicin is a CD22-targeting ADC that has been FDA approved for the treatment of adult patients with relapsed/refractory B-cell precursor ALL since last year. The therapy has been available to pediatric patients through a compassionate access program, but it has not been extensively evaluated in this population. The results of a retrospective analysis of pediatric patients who received at least 1 dose of inotuzumab ozogamicin were presented at ASCO in 2017. Among 29 patients with heavily pretreated disease the CR rate was 62%, 72% of whom achieved MRD negativity.³⁵

BARCELONA – Prenatal exposure to selective serotonin reuptake inhibitors late in pregnancy was associated with a significantly increased risk of anxious and/or depressed behaviors at 5 years of age in the prospective Norwegian Mother and Child Cohort Study.

Bruce Jancin/MDedge News

Other than that specific red flag, however, the outcomes of in utero exposure to maternal SSRIs were reassuringly benign. Prenatal exposure during early- or mid-pregnancy was not associated with increased risk of anxious/depressed behaviors, compared with nonexposure; that adverse effect was restricted to exposure at week 29 of pregnancy or later. Nor did in utero exposure to maternal SSRIs during any time in pregnancy pose an increased risk for pediatric externalizing, emotional, or social problems in this observational study of 8,359 Norwegian mother-child dyads, Josefina Castro-Fornieles, MD, PhD, observed at the annual congress of the European College of Neuropsychopharmacology.

The huge Norwegian study was among what she considers the four most important studies in child/adolescent psychiatry published through the first three quarters of 2018. The others she highlighted were a large longitudinal observational study that demonstrated that persistent maternal postnatal depression was strongly associated with a variety of pediatric behavioral disturbances documented during assessments at ages 3.5, 16, and 18 years; a Philadelphia study showing that multiple traumatic stressful events or any assaultive trauma experienced by children or adolescents were independently associated with significant psychopathology and neurocognitive deficits; and a Dutch brain MRI study that pinpointed a reduction in gray matter volume in the anterior cingulate cortex as a potential key mediator of the neurobiologic aftereffects of childhood sexual abuse.

She selected those studies because they shared a common theme, one that constituted her key take-home message: “When recording antecedents during a clinical assessment, both with adults and children, it is clear that we have to ask in a more detailed way – using validated scales and interviews if possible – about the mother’s prenatal problems, including psychopharmacological treatment. That is something we often don’t do in a sufficiently detailed way in our clinical practice. And it’s also important to ask about life events; abuse during childhood and adolescence can be really important. We can modulate our treatment depending upon whether there is an influence of any of these aspects,” said Dr. Castro-Fornieles, director of the Clinical Institute of Neuroscience at the Hospital Clinic of Barcelona and a recent past-president of the Spanish Society for Child and Adolescent Psychiatry.

The following are her Top 4 studies:

The Norwegian Mother and Child Cohort Study

The increased risk of anxious and/or depressed behaviors in children exposed to selective serotonin reuptake inhibitors (SSRIs) late in pregnancy did not emerge until the year-5 assessment; it wasn’t evident at the 1.5- or 3-year evaluations.

The investigators emphasized a key lesson from their study: The importance of following children with late-pregnancy exposure to maternal SSRI therapy for development of symptoms of anxiety and/or depression (J Am Acad Child Adolesc Psychiatry. 2018 Mar;57[3]:200-8). Dr. Castro-Fornieles strongly endorsed that recommendation. However, she noted what she considers an important limitation to the study: even though the University of Oslo investigators adjusted for numerous potential confounders in their risk models – including maternal body mass index, parity, education, smoking, substance use, breastfeeding, folic acid use, and other medications used during pregnancy – it’s not possible in a study such as this to control for genetic and environmental risk factors, which she suspects also were at work.

The Avon Longitudinal Study of Parents and Children in the United Kingdom

Maternal postnatal depression is common, affecting roughly 10% of mothers. But it is not invariably associated with adverse mental health outcomes in their children. This study of nearly 10,000 mothers and their children sought to identify which children were at most risk. Using the Edinburgh Postnatal Depression Scale, the international team of investigators categorized maternal postnatal depression as moderate, marked, or severe. The affective disorder was deemed persistent if scores on the Edinburgh scale were elevated at both 2 and 8 months after delivery.

Postnatal depression, whether persistent or not, was associated with roughly a 2- to 2.4-fold increase for child behavioral disturbances when assessed at age 3.5 years using the Rutter Total Problems Scale. But postnatal depression that was persistent was the real difference maker: It carried a much higher risk of adverse behavioral outcomes and cognitive deficits than did the nonpersistent version. Indeed, persistent severe postnatal depression was associated a 4.8-fold increased risk of behavioral problems at age 3.5 years, a 2.65-fold greater risk of markedly lower grades in mathematics at age 16 years, and a 7.4-fold increased prevalence of depression at 18 years of age. The investigators advised screening mothers during the first postpartum year in order to identify those with persistent postpartum depression (JAMA Psychiatry. 2018 Mar 1;75[3]:247-53).

Dr. Castro-Fornieles said an important shortcoming of the Avon study was that it did not record paternal data.

“The study didn’t consider depression or other functional measures in the father, his commitment to childrearing, and whether the family was together or divorced. I feel this is an important limitation in many studies. For me, it’s really important to consider what’s happening with the fathers,” she said.

Traumatic stress load, psychopathology, and cognition

An eye-opening report from the Philadelphia Neurodevelopmental Cohort documented a surprisingly high level of lifetime exposure to traumatic events among 9,498 youth aged 8-21 years, and the stepwise manner by which a greater traumatic stress load was associated with increasing severity of psychopathology and cognitive deficits. Notably, the study participants were recruited from general pediatric clinics in the Children’s Hospital of Philadelphia health care network; they were not patients seeking psychiatric help. And yet, extensive structured psychiatric evaluation showed that 23% of them had a history of one traumatic stressful event, 12% had two, and 1% had three or more.

In analyses adjusted for lifetime history of depression or PTSD, a higher traumatic event load was associated with increased risk of externalizing behaviors, mood/anxiety disorders, psychosis spectrum, and fear. Moreover, a high trauma stress load was associated with a 5.3-fold increased risk of suicidal thoughts and a 3.2-fold increased likelihood of cannabis use, compared with youth who had never been exposed to a traumatic event. Increased stress load also was associated with worse cognitive performance on tests of executive functioning, social cognition, and complex reasoning.

A history of assaultive trauma – being badly beaten, threatened with a weapon, or sexually abused – was associated with more severe psychopathology than in subjects with a history of nonassaultive traumatic events (Psychol Med. 2018 Apr 15:1-10).

Session moderator Carmen Moreno, MD, a child and adolescent psychiatrist at Gregorio Marañón University Hospital in Madrid, commented, “It was striking to me that the prevalence of childhood traumatic events was so high in a pediatric community sample. Is the measure the investigators chose the right measure?”

Dr. Castro-Fornieles replied that it was a very sensitive measure, in that an event many would consider part of normal life – for example, seeing a relative’s body on display in a funeral home – was scored as a traumatic exposure.

“Only one exposure is not that important,” she said. “The impact increases as you increase the number of traumatic events. And also the assaultive ones.”

Sexual abuse leaves a fingerprint

Investigators at Leiden (the Netherlands) University performed neuroimaging that looked at numerous brain regions of interest in 21 adolescents with childhood sexual abuse–related PTSD and 25 matched healthy controls. The standout finding was that the dorsal gray matter volume of the anterior cingulate cortex was significantly smaller in the teens with PTSD and a history of childhood sexual abuse (Eur Neuropsychopharmacol. 2017 Nov;27[11]:1163-71).

The investigators wanted a pure sample of patients with PTSD after childhood sexual abuse, so they excluded individuals who had experienced childhood sexual abuse and had a diagnosis of attention-deficit/hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder, conduct disorder, pervasive developmental disorder, bipolar disorder, or a psychotic disorder. That is both a strength and a limitation of the study, in Dr. Castro-Fornieles’ view.

“To me, that excludes too many of the children we see in our clinical settings. This work needs to be corroborated in a bigger sample, including patients with other diagnoses,” she said.

She reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

BARCELONA – Prenatal exposure to selective serotonin reuptake inhibitors late in pregnancy was associated with a significantly increased risk of anxious and/or depressed behaviors at 5 years of age in the prospective Norwegian Mother and Child Cohort Study.

Bruce Jancin/MDedge News

Other than that specific red flag, however, the outcomes of in utero exposure to maternal SSRIs were reassuringly benign. Prenatal exposure during early- or mid-pregnancy was not associated with increased risk of anxious/depressed behaviors, compared with nonexposure; that adverse effect was restricted to exposure at week 29 of pregnancy or later. Nor did in utero exposure to maternal SSRIs during any time in pregnancy pose an increased risk for pediatric externalizing, emotional, or social problems in this observational study of 8,359 Norwegian mother-child dyads, Josefina Castro-Fornieles, MD, PhD, observed at the annual congress of the European College of Neuropsychopharmacology.

The huge Norwegian study was among what she considers the four most important studies in child/adolescent psychiatry published through the first three quarters of 2018. The others she highlighted were a large longitudinal observational study that demonstrated that persistent maternal postnatal depression was strongly associated with a variety of pediatric behavioral disturbances documented during assessments at ages 3.5, 16, and 18 years; a Philadelphia study showing that multiple traumatic stressful events or any assaultive trauma experienced by children or adolescents were independently associated with significant psychopathology and neurocognitive deficits; and a Dutch brain MRI study that pinpointed a reduction in gray matter volume in the anterior cingulate cortex as a potential key mediator of the neurobiologic aftereffects of childhood sexual abuse.

She selected those studies because they shared a common theme, one that constituted her key take-home message: “When recording antecedents during a clinical assessment, both with adults and children, it is clear that we have to ask in a more detailed way – using validated scales and interviews if possible – about the mother’s prenatal problems, including psychopharmacological treatment. That is something we often don’t do in a sufficiently detailed way in our clinical practice. And it’s also important to ask about life events; abuse during childhood and adolescence can be really important. We can modulate our treatment depending upon whether there is an influence of any of these aspects,” said Dr. Castro-Fornieles, director of the Clinical Institute of Neuroscience at the Hospital Clinic of Barcelona and a recent past-president of the Spanish Society for Child and Adolescent Psychiatry.

The following are her Top 4 studies:

The Norwegian Mother and Child Cohort Study

The increased risk of anxious and/or depressed behaviors in children exposed to selective serotonin reuptake inhibitors (SSRIs) late in pregnancy did not emerge until the year-5 assessment; it wasn’t evident at the 1.5- or 3-year evaluations.

The investigators emphasized a key lesson from their study: The importance of following children with late-pregnancy exposure to maternal SSRI therapy for development of symptoms of anxiety and/or depression (J Am Acad Child Adolesc Psychiatry. 2018 Mar;57[3]:200-8). Dr. Castro-Fornieles strongly endorsed that recommendation. However, she noted what she considers an important limitation to the study: even though the University of Oslo investigators adjusted for numerous potential confounders in their risk models – including maternal body mass index, parity, education, smoking, substance use, breastfeeding, folic acid use, and other medications used during pregnancy – it’s not possible in a study such as this to control for genetic and environmental risk factors, which she suspects also were at work.

The Avon Longitudinal Study of Parents and Children in the United Kingdom

Maternal postnatal depression is common, affecting roughly 10% of mothers. But it is not invariably associated with adverse mental health outcomes in their children. This study of nearly 10,000 mothers and their children sought to identify which children were at most risk. Using the Edinburgh Postnatal Depression Scale, the international team of investigators categorized maternal postnatal depression as moderate, marked, or severe. The affective disorder was deemed persistent if scores on the Edinburgh scale were elevated at both 2 and 8 months after delivery.

Postnatal depression, whether persistent or not, was associated with roughly a 2- to 2.4-fold increase for child behavioral disturbances when assessed at age 3.5 years using the Rutter Total Problems Scale. But postnatal depression that was persistent was the real difference maker: It carried a much higher risk of adverse behavioral outcomes and cognitive deficits than did the nonpersistent version. Indeed, persistent severe postnatal depression was associated a 4.8-fold increased risk of behavioral problems at age 3.5 years, a 2.65-fold greater risk of markedly lower grades in mathematics at age 16 years, and a 7.4-fold increased prevalence of depression at 18 years of age. The investigators advised screening mothers during the first postpartum year in order to identify those with persistent postpartum depression (JAMA Psychiatry. 2018 Mar 1;75[3]:247-53).

Dr. Castro-Fornieles said an important shortcoming of the Avon study was that it did not record paternal data.

“The study didn’t consider depression or other functional measures in the father, his commitment to childrearing, and whether the family was together or divorced. I feel this is an important limitation in many studies. For me, it’s really important to consider what’s happening with the fathers,” she said.

Traumatic stress load, psychopathology, and cognition

An eye-opening report from the Philadelphia Neurodevelopmental Cohort documented a surprisingly high level of lifetime exposure to traumatic events among 9,498 youth aged 8-21 years, and the stepwise manner by which a greater traumatic stress load was associated with increasing severity of psychopathology and cognitive deficits. Notably, the study participants were recruited from general pediatric clinics in the Children’s Hospital of Philadelphia health care network; they were not patients seeking psychiatric help. And yet, extensive structured psychiatric evaluation showed that 23% of them had a history of one traumatic stressful event, 12% had two, and 1% had three or more.

In analyses adjusted for lifetime history of depression or PTSD, a higher traumatic event load was associated with increased risk of externalizing behaviors, mood/anxiety disorders, psychosis spectrum, and fear. Moreover, a high trauma stress load was associated with a 5.3-fold increased risk of suicidal thoughts and a 3.2-fold increased likelihood of cannabis use, compared with youth who had never been exposed to a traumatic event. Increased stress load also was associated with worse cognitive performance on tests of executive functioning, social cognition, and complex reasoning.

A history of assaultive trauma – being badly beaten, threatened with a weapon, or sexually abused – was associated with more severe psychopathology than in subjects with a history of nonassaultive traumatic events (Psychol Med. 2018 Apr 15:1-10).

Session moderator Carmen Moreno, MD, a child and adolescent psychiatrist at Gregorio Marañón University Hospital in Madrid, commented, “It was striking to me that the prevalence of childhood traumatic events was so high in a pediatric community sample. Is the measure the investigators chose the right measure?”

Dr. Castro-Fornieles replied that it was a very sensitive measure, in that an event many would consider part of normal life – for example, seeing a relative’s body on display in a funeral home – was scored as a traumatic exposure.

“Only one exposure is not that important,” she said. “The impact increases as you increase the number of traumatic events. And also the assaultive ones.”

Sexual abuse leaves a fingerprint

Investigators at Leiden (the Netherlands) University performed neuroimaging that looked at numerous brain regions of interest in 21 adolescents with childhood sexual abuse–related PTSD and 25 matched healthy controls. The standout finding was that the dorsal gray matter volume of the anterior cingulate cortex was significantly smaller in the teens with PTSD and a history of childhood sexual abuse (Eur Neuropsychopharmacol. 2017 Nov;27[11]:1163-71).

The investigators wanted a pure sample of patients with PTSD after childhood sexual abuse, so they excluded individuals who had experienced childhood sexual abuse and had a diagnosis of attention-deficit/hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder, conduct disorder, pervasive developmental disorder, bipolar disorder, or a psychotic disorder. That is both a strength and a limitation of the study, in Dr. Castro-Fornieles’ view.

“To me, that excludes too many of the children we see in our clinical settings. This work needs to be corroborated in a bigger sample, including patients with other diagnoses,” she said.

She reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

BARCELONA – Prenatal exposure to selective serotonin reuptake inhibitors late in pregnancy was associated with a significantly increased risk of anxious and/or depressed behaviors at 5 years of age in the prospective Norwegian Mother and Child Cohort Study.

Bruce Jancin/MDedge News

Other than that specific red flag, however, the outcomes of in utero exposure to maternal SSRIs were reassuringly benign. Prenatal exposure during early- or mid-pregnancy was not associated with increased risk of anxious/depressed behaviors, compared with nonexposure; that adverse effect was restricted to exposure at week 29 of pregnancy or later. Nor did in utero exposure to maternal SSRIs during any time in pregnancy pose an increased risk for pediatric externalizing, emotional, or social problems in this observational study of 8,359 Norwegian mother-child dyads, Josefina Castro-Fornieles, MD, PhD, observed at the annual congress of the European College of Neuropsychopharmacology.

The huge Norwegian study was among what she considers the four most important studies in child/adolescent psychiatry published through the first three quarters of 2018. The others she highlighted were a large longitudinal observational study that demonstrated that persistent maternal postnatal depression was strongly associated with a variety of pediatric behavioral disturbances documented during assessments at ages 3.5, 16, and 18 years; a Philadelphia study showing that multiple traumatic stressful events or any assaultive trauma experienced by children or adolescents were independently associated with significant psychopathology and neurocognitive deficits; and a Dutch brain MRI study that pinpointed a reduction in gray matter volume in the anterior cingulate cortex as a potential key mediator of the neurobiologic aftereffects of childhood sexual abuse.

She selected those studies because they shared a common theme, one that constituted her key take-home message: “When recording antecedents during a clinical assessment, both with adults and children, it is clear that we have to ask in a more detailed way – using validated scales and interviews if possible – about the mother’s prenatal problems, including psychopharmacological treatment. That is something we often don’t do in a sufficiently detailed way in our clinical practice. And it’s also important to ask about life events; abuse during childhood and adolescence can be really important. We can modulate our treatment depending upon whether there is an influence of any of these aspects,” said Dr. Castro-Fornieles, director of the Clinical Institute of Neuroscience at the Hospital Clinic of Barcelona and a recent past-president of the Spanish Society for Child and Adolescent Psychiatry.

The following are her Top 4 studies:

The Norwegian Mother and Child Cohort Study

The increased risk of anxious and/or depressed behaviors in children exposed to selective serotonin reuptake inhibitors (SSRIs) late in pregnancy did not emerge until the year-5 assessment; it wasn’t evident at the 1.5- or 3-year evaluations.

The investigators emphasized a key lesson from their study: The importance of following children with late-pregnancy exposure to maternal SSRI therapy for development of symptoms of anxiety and/or depression (J Am Acad Child Adolesc Psychiatry. 2018 Mar;57[3]:200-8). Dr. Castro-Fornieles strongly endorsed that recommendation. However, she noted what she considers an important limitation to the study: even though the University of Oslo investigators adjusted for numerous potential confounders in their risk models – including maternal body mass index, parity, education, smoking, substance use, breastfeeding, folic acid use, and other medications used during pregnancy – it’s not possible in a study such as this to control for genetic and environmental risk factors, which she suspects also were at work.

The Avon Longitudinal Study of Parents and Children in the United Kingdom

Maternal postnatal depression is common, affecting roughly 10% of mothers. But it is not invariably associated with adverse mental health outcomes in their children. This study of nearly 10,000 mothers and their children sought to identify which children were at most risk. Using the Edinburgh Postnatal Depression Scale, the international team of investigators categorized maternal postnatal depression as moderate, marked, or severe. The affective disorder was deemed persistent if scores on the Edinburgh scale were elevated at both 2 and 8 months after delivery.

Postnatal depression, whether persistent or not, was associated with roughly a 2- to 2.4-fold increase for child behavioral disturbances when assessed at age 3.5 years using the Rutter Total Problems Scale. But postnatal depression that was persistent was the real difference maker: It carried a much higher risk of adverse behavioral outcomes and cognitive deficits than did the nonpersistent version. Indeed, persistent severe postnatal depression was associated a 4.8-fold increased risk of behavioral problems at age 3.5 years, a 2.65-fold greater risk of markedly lower grades in mathematics at age 16 years, and a 7.4-fold increased prevalence of depression at 18 years of age. The investigators advised screening mothers during the first postpartum year in order to identify those with persistent postpartum depression (JAMA Psychiatry. 2018 Mar 1;75[3]:247-53).

Dr. Castro-Fornieles said an important shortcoming of the Avon study was that it did not record paternal data.

“The study didn’t consider depression or other functional measures in the father, his commitment to childrearing, and whether the family was together or divorced. I feel this is an important limitation in many studies. For me, it’s really important to consider what’s happening with the fathers,” she said.

Traumatic stress load, psychopathology, and cognition

An eye-opening report from the Philadelphia Neurodevelopmental Cohort documented a surprisingly high level of lifetime exposure to traumatic events among 9,498 youth aged 8-21 years, and the stepwise manner by which a greater traumatic stress load was associated with increasing severity of psychopathology and cognitive deficits. Notably, the study participants were recruited from general pediatric clinics in the Children’s Hospital of Philadelphia health care network; they were not patients seeking psychiatric help. And yet, extensive structured psychiatric evaluation showed that 23% of them had a history of one traumatic stressful event, 12% had two, and 1% had three or more.

In analyses adjusted for lifetime history of depression or PTSD, a higher traumatic event load was associated with increased risk of externalizing behaviors, mood/anxiety disorders, psychosis spectrum, and fear. Moreover, a high trauma stress load was associated with a 5.3-fold increased risk of suicidal thoughts and a 3.2-fold increased likelihood of cannabis use, compared with youth who had never been exposed to a traumatic event. Increased stress load also was associated with worse cognitive performance on tests of executive functioning, social cognition, and complex reasoning.

A history of assaultive trauma – being badly beaten, threatened with a weapon, or sexually abused – was associated with more severe psychopathology than in subjects with a history of nonassaultive traumatic events (Psychol Med. 2018 Apr 15:1-10).

Session moderator Carmen Moreno, MD, a child and adolescent psychiatrist at Gregorio Marañón University Hospital in Madrid, commented, “It was striking to me that the prevalence of childhood traumatic events was so high in a pediatric community sample. Is the measure the investigators chose the right measure?”

Dr. Castro-Fornieles replied that it was a very sensitive measure, in that an event many would consider part of normal life – for example, seeing a relative’s body on display in a funeral home – was scored as a traumatic exposure.

“Only one exposure is not that important,” she said. “The impact increases as you increase the number of traumatic events. And also the assaultive ones.”

Sexual abuse leaves a fingerprint

Investigators at Leiden (the Netherlands) University performed neuroimaging that looked at numerous brain regions of interest in 21 adolescents with childhood sexual abuse–related PTSD and 25 matched healthy controls. The standout finding was that the dorsal gray matter volume of the anterior cingulate cortex was significantly smaller in the teens with PTSD and a history of childhood sexual abuse (Eur Neuropsychopharmacol. 2017 Nov;27[11]:1163-71).

The investigators wanted a pure sample of patients with PTSD after childhood sexual abuse, so they excluded individuals who had experienced childhood sexual abuse and had a diagnosis of attention-deficit/hyperactivity disorder, oppositional defiant disorder, obsessive-compulsive disorder, conduct disorder, pervasive developmental disorder, bipolar disorder, or a psychotic disorder. That is both a strength and a limitation of the study, in Dr. Castro-Fornieles’ view.

“To me, that excludes too many of the children we see in our clinical settings. This work needs to be corroborated in a bigger sample, including patients with other diagnoses,” she said.

She reported having no financial conflicts regarding her presentation.
 

bjancin@mdedge.com

The change in policy eliminating nonmedical vaccine exemptions in California (Senate Bill 277) led to a 250% increase in requests for medical exemptions, according to data from interviews with health officials and immunization staff after implementation of the policy.

©LeventKonuk/Thinkstock.com

In a study published in Pediatrics, Salini Mohanty, DrPH, of the University of Pennsylvania School of Nursing, Philadelphia, and her colleagues conducted semistructured phone interviews with 40 health officers and immunization staff who represented 35 of 61 California heath jurisdictions. The interviews occurred between August 2017 and September 2017, and participants discussed their experiences with medical exemption requests after the policy change.

Although the percentage of fully vaccinated kindergarten students in California increased from 93% in 2015-2016 to 95% in 2017-2018, and the rate of personal belief exemptions declined, overall medical exemption requests rose 250% from 0.2% in 2015-2016 to 0.7% 2017-2018, the researchers noted.

They identified four main issues based on participant responses: the role of stakeholders, the review of medical exemptions received by schools, the medical exemptions perceived as problematic, and the general frustration and concern over medical exemptions.

Based on the interviews, one concerning subtheme involved reports that some physicians wrote medical exemptions for vaccine-hesitant parents based on conditions such as allergies and autoimmune diseases.

“The Internet provides access to physicians who are willing to sign off on exemptions and to websites used to instruct parents on how to get physicians to approve medical exemptions,” the researchers said.

“Understanding how physicians interpret the law is important because they are writing the medical exemptions,” Dr. Mohanty and her associates noted, and they proposed increased outreach and education of physicians about the law to reduce problematic medical exemptions.

Many health officials expressed frustration with their inability to review medical exemptions submitted directly to schools. In fact, interviewees cited one California jurisdiction that was named in a lawsuit for attempting to track medical exemptions, “which had an impact on other jurisdictions decision to track,” they said.

Officials also expressed concern that parents’ use of medical exemptions to replace personal belief exemptions would reduce herd immunity. Overall, regions with high levels of personal belief exemptions showed the largest increases in medical exemptions after SB277, which could put these regions at increased risk for vaccine-preventable outbreaks, the researchers noted.

There also were reports of physicians “who advertised medical exemptions online for a fee.” Officials also reported “receiving medical exemptions signed by physicians who do not typically treat children (cardiologists, dermatologists, surgeons, and physicians at medical marijuana dispensaries) and by unauthorized nonphysician providers, including nurse practitioners,” Dr. Mohanty and her associates said.

The study findings were limited by several factors including small sample size and potential recall bias, the researchers noted. However, the study is the first to include perspectives of local health officials after a change in vaccine exemption policy.

The National Institutes of Health supported the study. Dr. Mohanty had no financial conflicts to disclose; one coauthor disclosed relationships with Merck, Pfizer, and Walgreens.

SOURCE: Mohanty S et al. Pediatrics. 2018. doi: 10.1542/peds.2018-1051.

The change in policy eliminating nonmedical vaccine exemptions in California (Senate Bill 277) led to a 250% increase in requests for medical exemptions, according to data from interviews with health officials and immunization staff after implementation of the policy.

©LeventKonuk/Thinkstock.com

In a study published in Pediatrics, Salini Mohanty, DrPH, of the University of Pennsylvania School of Nursing, Philadelphia, and her colleagues conducted semistructured phone interviews with 40 health officers and immunization staff who represented 35 of 61 California heath jurisdictions. The interviews occurred between August 2017 and September 2017, and participants discussed their experiences with medical exemption requests after the policy change.

Although the percentage of fully vaccinated kindergarten students in California increased from 93% in 2015-2016 to 95% in 2017-2018, and the rate of personal belief exemptions declined, overall medical exemption requests rose 250% from 0.2% in 2015-2016 to 0.7% 2017-2018, the researchers noted.

They identified four main issues based on participant responses: the role of stakeholders, the review of medical exemptions received by schools, the medical exemptions perceived as problematic, and the general frustration and concern over medical exemptions.

Based on the interviews, one concerning subtheme involved reports that some physicians wrote medical exemptions for vaccine-hesitant parents based on conditions such as allergies and autoimmune diseases.

“The Internet provides access to physicians who are willing to sign off on exemptions and to websites used to instruct parents on how to get physicians to approve medical exemptions,” the researchers said.

“Understanding how physicians interpret the law is important because they are writing the medical exemptions,” Dr. Mohanty and her associates noted, and they proposed increased outreach and education of physicians about the law to reduce problematic medical exemptions.

Many health officials expressed frustration with their inability to review medical exemptions submitted directly to schools. In fact, interviewees cited one California jurisdiction that was named in a lawsuit for attempting to track medical exemptions, “which had an impact on other jurisdictions decision to track,” they said.

Officials also expressed concern that parents’ use of medical exemptions to replace personal belief exemptions would reduce herd immunity. Overall, regions with high levels of personal belief exemptions showed the largest increases in medical exemptions after SB277, which could put these regions at increased risk for vaccine-preventable outbreaks, the researchers noted.

There also were reports of physicians “who advertised medical exemptions online for a fee.” Officials also reported “receiving medical exemptions signed by physicians who do not typically treat children (cardiologists, dermatologists, surgeons, and physicians at medical marijuana dispensaries) and by unauthorized nonphysician providers, including nurse practitioners,” Dr. Mohanty and her associates said.

The study findings were limited by several factors including small sample size and potential recall bias, the researchers noted. However, the study is the first to include perspectives of local health officials after a change in vaccine exemption policy.

The National Institutes of Health supported the study. Dr. Mohanty had no financial conflicts to disclose; one coauthor disclosed relationships with Merck, Pfizer, and Walgreens.

SOURCE: Mohanty S et al. Pediatrics. 2018. doi: 10.1542/peds.2018-1051.

The change in policy eliminating nonmedical vaccine exemptions in California (Senate Bill 277) led to a 250% increase in requests for medical exemptions, according to data from interviews with health officials and immunization staff after implementation of the policy.

©LeventKonuk/Thinkstock.com

In a study published in Pediatrics, Salini Mohanty, DrPH, of the University of Pennsylvania School of Nursing, Philadelphia, and her colleagues conducted semistructured phone interviews with 40 health officers and immunization staff who represented 35 of 61 California heath jurisdictions. The interviews occurred between August 2017 and September 2017, and participants discussed their experiences with medical exemption requests after the policy change.

Although the percentage of fully vaccinated kindergarten students in California increased from 93% in 2015-2016 to 95% in 2017-2018, and the rate of personal belief exemptions declined, overall medical exemption requests rose 250% from 0.2% in 2015-2016 to 0.7% 2017-2018, the researchers noted.

They identified four main issues based on participant responses: the role of stakeholders, the review of medical exemptions received by schools, the medical exemptions perceived as problematic, and the general frustration and concern over medical exemptions.

Based on the interviews, one concerning subtheme involved reports that some physicians wrote medical exemptions for vaccine-hesitant parents based on conditions such as allergies and autoimmune diseases.

“The Internet provides access to physicians who are willing to sign off on exemptions and to websites used to instruct parents on how to get physicians to approve medical exemptions,” the researchers said.

“Understanding how physicians interpret the law is important because they are writing the medical exemptions,” Dr. Mohanty and her associates noted, and they proposed increased outreach and education of physicians about the law to reduce problematic medical exemptions.

Many health officials expressed frustration with their inability to review medical exemptions submitted directly to schools. In fact, interviewees cited one California jurisdiction that was named in a lawsuit for attempting to track medical exemptions, “which had an impact on other jurisdictions decision to track,” they said.

Officials also expressed concern that parents’ use of medical exemptions to replace personal belief exemptions would reduce herd immunity. Overall, regions with high levels of personal belief exemptions showed the largest increases in medical exemptions after SB277, which could put these regions at increased risk for vaccine-preventable outbreaks, the researchers noted.

There also were reports of physicians “who advertised medical exemptions online for a fee.” Officials also reported “receiving medical exemptions signed by physicians who do not typically treat children (cardiologists, dermatologists, surgeons, and physicians at medical marijuana dispensaries) and by unauthorized nonphysician providers, including nurse practitioners,” Dr. Mohanty and her associates said.

The study findings were limited by several factors including small sample size and potential recall bias, the researchers noted. However, the study is the first to include perspectives of local health officials after a change in vaccine exemption policy.

The National Institutes of Health supported the study. Dr. Mohanty had no financial conflicts to disclose; one coauthor disclosed relationships with Merck, Pfizer, and Walgreens.

SOURCE: Mohanty S et al. Pediatrics. 2018. doi: 10.1542/peds.2018-1051.