Commentary

Contemporary critiques of Memorial and Veterans Day celebrations have emphasized that while ceremonies and celebrations are culturally requisite means of demonstrating a society’s respect and gratitude for those who gave their lives and health in the country’s cause—it is not enough. These holidays have immense symbolic significance to remind the nation of the sacrifice of those who bore arms in its service. An enduring and substantive impact on veterans will require real work done on their behalf. Through its representative institutions, such as the US Departments of Defense (DoD) and Veterans Affairs (VA) and citizens’ voluntary efforts, the public must provide practical assistance to veterans and their families.²

Memorial Day honors our sacred dead who lost their lives defending freedom. In federal practice and the larger community, we are duty-bound to try and restore the things war took from these wounded warriors and in whatever measure is possible to return them to the land of the fully living. Except in memory, we cannot bring back the dead. And while life is the most precious gift, those who survived the battlefield too often lose much that matters to a meaningful human life—friends, family, livelihood, housing, self-worth, peace of heart, soundness of mind, and health of the body.

One such recent initiative of reclamation is the Green Alert. Readers are likely familiar with Amber alerts for abducted children and Silver Alerts for older adults often with cognitive impairment who are lost. The Green Alert is a similar program deploying media and law enforcement to search for missing veterans believed to be vulnerable to harm because of a medical or psychiatric illness related to their service.

In 2017 Wisconsin became the first state to pass Green Alert legislation. The Missing Veterans at Risk Act lists 2 criteria that trigger a Green Alert: There is a reason to believe that the veteran at risk is missing due to a physical or mental health condition or that the veteran at risk is missing due to a physical or mental health condition. Relevant to the readers of Federal Practitioner, in Wisconsin, Green Alerts can be issued on behalf of missing veterans, and active-duty guard and reserve members and thus cover almost all the ranks of US military service.³ When law enforcement receives a report of a missing veteran as defined in the act within 72 hours of their disappearance, a Green Alert is issued. The statute directs the US Department of Justice to permit law enforcement to access the crime notification network to notify the media to broadcast pertinent information about the missing veteran.

As of this writing, Delaware, Kentucky, Connecticut, and Texas have passed similar laws, and legislatures in other states are considering bills, as is Congress.⁴ The sponsorship of the National Green Alert Act is bipartisan. Its stated purpose is: to develop interagency Green Alert systems that would be used when a veteran “goes missing” and “for other purposes.”⁵

The program’s potential to reduce the number of veterans who die by suicide every day has understandably attracted the attention of legislators and the public.⁶ The Cost of War project disclosed the terrible irony that at least 4 times as many post-9/11 service members died by suicide as perished in the combat that Memorial Day traditionally commemorates.⁷ As with many veteran-related laws, the initial Green Alert in Wisconsin was borne out of tragedy and passed through the heroic advocacy of bereaved and outraged family members.⁸ The DoD and VA, Congress, veterans service organizations, and the loved ones of servicemembers desperately want to turn this devastating tide of self-destruction through any means possible.

It seems almost a blasphemous betrayal of our public trust to raise ethical questions about Green Alerts. Yet that must happen if we ensure that these laws achieve their intended aims of preventing harm. For many veterans, these laws may indeed be lifesaving. However, a 2019 National Public Radio report suggested that these laws may, in some cases, result in several unintended harms.⁹ On first reading, it is worthy, even our duty, to extend the public health safety net for children who are victims of abduction and individuals with dementia to vulnerable veterans secondary to the mental and physical wounds of service.

When the service member is located, the alert is canceled. Nevertheless, their data remains in all the protean forms of media now available. In these searches for service members thought to be lost, there is a risk of violating their privacy if too much protected health information is made widely public. These breaches of confidentiality can further exacerbate the already too prevalent stigmatization of mental illness in the military, which has been a formidable obstacle to persuading those in uniform to seek treatment.¹⁰ As J.R.R. Tolkien has noted, not every person who “wanders” is lost.¹ A veteran may leave his home for some period, even without notifying anyone, without being in grave and imminent danger. The diagnoses we health care professionals assign to patients are wide conceptual nets full of empirical holes: they are poorly predictive and protective mechanisms.¹¹ A broadly written or vague law leaves latitude for bias, discrimination, liability, and fear to drive decisions that to be ethically justifiable require consistency, transparency, equity, and expertise. Much more research is needed to develop situational awareness, scientific accuracy, and clinical reliability to understand when, how, and for whom Green Alerts are genuinely beneficial.

These are not insurmountable questions. The experts and stakeholders appointed to the interagency committee the national Green Alert proposes will work to address these problems. Yet, unless they and we look bravely at the thorny issues these laudable laws present, it will be challenging to achieve their purpose to safeguard the dignity, safety, as well as autonomy and well-being of service members.

Contemporary critiques of Memorial and Veterans Day celebrations have emphasized that while ceremonies and celebrations are culturally requisite means of demonstrating a society’s respect and gratitude for those who gave their lives and health in the country’s cause—it is not enough. These holidays have immense symbolic significance to remind the nation of the sacrifice of those who bore arms in its service. An enduring and substantive impact on veterans will require real work done on their behalf. Through its representative institutions, such as the US Departments of Defense (DoD) and Veterans Affairs (VA) and citizens’ voluntary efforts, the public must provide practical assistance to veterans and their families.²

Memorial Day honors our sacred dead who lost their lives defending freedom. In federal practice and the larger community, we are duty-bound to try and restore the things war took from these wounded warriors and in whatever measure is possible to return them to the land of the fully living. Except in memory, we cannot bring back the dead. And while life is the most precious gift, those who survived the battlefield too often lose much that matters to a meaningful human life—friends, family, livelihood, housing, self-worth, peace of heart, soundness of mind, and health of the body.

One such recent initiative of reclamation is the Green Alert. Readers are likely familiar with Amber alerts for abducted children and Silver Alerts for older adults often with cognitive impairment who are lost. The Green Alert is a similar program deploying media and law enforcement to search for missing veterans believed to be vulnerable to harm because of a medical or psychiatric illness related to their service.

In 2017 Wisconsin became the first state to pass Green Alert legislation. The Missing Veterans at Risk Act lists 2 criteria that trigger a Green Alert: There is a reason to believe that the veteran at risk is missing due to a physical or mental health condition or that the veteran at risk is missing due to a physical or mental health condition. Relevant to the readers of Federal Practitioner, in Wisconsin, Green Alerts can be issued on behalf of missing veterans, and active-duty guard and reserve members and thus cover almost all the ranks of US military service.³ When law enforcement receives a report of a missing veteran as defined in the act within 72 hours of their disappearance, a Green Alert is issued. The statute directs the US Department of Justice to permit law enforcement to access the crime notification network to notify the media to broadcast pertinent information about the missing veteran.

As of this writing, Delaware, Kentucky, Connecticut, and Texas have passed similar laws, and legislatures in other states are considering bills, as is Congress.⁴ The sponsorship of the National Green Alert Act is bipartisan. Its stated purpose is: to develop interagency Green Alert systems that would be used when a veteran “goes missing” and “for other purposes.”⁵

The program’s potential to reduce the number of veterans who die by suicide every day has understandably attracted the attention of legislators and the public.⁶ The Cost of War project disclosed the terrible irony that at least 4 times as many post-9/11 service members died by suicide as perished in the combat that Memorial Day traditionally commemorates.⁷ As with many veteran-related laws, the initial Green Alert in Wisconsin was borne out of tragedy and passed through the heroic advocacy of bereaved and outraged family members.⁸ The DoD and VA, Congress, veterans service organizations, and the loved ones of servicemembers desperately want to turn this devastating tide of self-destruction through any means possible.

It seems almost a blasphemous betrayal of our public trust to raise ethical questions about Green Alerts. Yet that must happen if we ensure that these laws achieve their intended aims of preventing harm. For many veterans, these laws may indeed be lifesaving. However, a 2019 National Public Radio report suggested that these laws may, in some cases, result in several unintended harms.⁹ On first reading, it is worthy, even our duty, to extend the public health safety net for children who are victims of abduction and individuals with dementia to vulnerable veterans secondary to the mental and physical wounds of service.

When the service member is located, the alert is canceled. Nevertheless, their data remains in all the protean forms of media now available. In these searches for service members thought to be lost, there is a risk of violating their privacy if too much protected health information is made widely public. These breaches of confidentiality can further exacerbate the already too prevalent stigmatization of mental illness in the military, which has been a formidable obstacle to persuading those in uniform to seek treatment.¹⁰ As J.R.R. Tolkien has noted, not every person who “wanders” is lost.¹ A veteran may leave his home for some period, even without notifying anyone, without being in grave and imminent danger. The diagnoses we health care professionals assign to patients are wide conceptual nets full of empirical holes: they are poorly predictive and protective mechanisms.¹¹ A broadly written or vague law leaves latitude for bias, discrimination, liability, and fear to drive decisions that to be ethically justifiable require consistency, transparency, equity, and expertise. Much more research is needed to develop situational awareness, scientific accuracy, and clinical reliability to understand when, how, and for whom Green Alerts are genuinely beneficial.

These are not insurmountable questions. The experts and stakeholders appointed to the interagency committee the national Green Alert proposes will work to address these problems. Yet, unless they and we look bravely at the thorny issues these laudable laws present, it will be challenging to achieve their purpose to safeguard the dignity, safety, as well as autonomy and well-being of service members.

Contemporary critiques of Memorial and Veterans Day celebrations have emphasized that while ceremonies and celebrations are culturally requisite means of demonstrating a society’s respect and gratitude for those who gave their lives and health in the country’s cause—it is not enough. These holidays have immense symbolic significance to remind the nation of the sacrifice of those who bore arms in its service. An enduring and substantive impact on veterans will require real work done on their behalf. Through its representative institutions, such as the US Departments of Defense (DoD) and Veterans Affairs (VA) and citizens’ voluntary efforts, the public must provide practical assistance to veterans and their families.²

Memorial Day honors our sacred dead who lost their lives defending freedom. In federal practice and the larger community, we are duty-bound to try and restore the things war took from these wounded warriors and in whatever measure is possible to return them to the land of the fully living. Except in memory, we cannot bring back the dead. And while life is the most precious gift, those who survived the battlefield too often lose much that matters to a meaningful human life—friends, family, livelihood, housing, self-worth, peace of heart, soundness of mind, and health of the body.

One such recent initiative of reclamation is the Green Alert. Readers are likely familiar with Amber alerts for abducted children and Silver Alerts for older adults often with cognitive impairment who are lost. The Green Alert is a similar program deploying media and law enforcement to search for missing veterans believed to be vulnerable to harm because of a medical or psychiatric illness related to their service.

In 2017 Wisconsin became the first state to pass Green Alert legislation. The Missing Veterans at Risk Act lists 2 criteria that trigger a Green Alert: There is a reason to believe that the veteran at risk is missing due to a physical or mental health condition or that the veteran at risk is missing due to a physical or mental health condition. Relevant to the readers of Federal Practitioner, in Wisconsin, Green Alerts can be issued on behalf of missing veterans, and active-duty guard and reserve members and thus cover almost all the ranks of US military service.³ When law enforcement receives a report of a missing veteran as defined in the act within 72 hours of their disappearance, a Green Alert is issued. The statute directs the US Department of Justice to permit law enforcement to access the crime notification network to notify the media to broadcast pertinent information about the missing veteran.

As of this writing, Delaware, Kentucky, Connecticut, and Texas have passed similar laws, and legislatures in other states are considering bills, as is Congress.⁴ The sponsorship of the National Green Alert Act is bipartisan. Its stated purpose is: to develop interagency Green Alert systems that would be used when a veteran “goes missing” and “for other purposes.”⁵

The program’s potential to reduce the number of veterans who die by suicide every day has understandably attracted the attention of legislators and the public.⁶ The Cost of War project disclosed the terrible irony that at least 4 times as many post-9/11 service members died by suicide as perished in the combat that Memorial Day traditionally commemorates.⁷ As with many veteran-related laws, the initial Green Alert in Wisconsin was borne out of tragedy and passed through the heroic advocacy of bereaved and outraged family members.⁸ The DoD and VA, Congress, veterans service organizations, and the loved ones of servicemembers desperately want to turn this devastating tide of self-destruction through any means possible.

It seems almost a blasphemous betrayal of our public trust to raise ethical questions about Green Alerts. Yet that must happen if we ensure that these laws achieve their intended aims of preventing harm. For many veterans, these laws may indeed be lifesaving. However, a 2019 National Public Radio report suggested that these laws may, in some cases, result in several unintended harms.⁹ On first reading, it is worthy, even our duty, to extend the public health safety net for children who are victims of abduction and individuals with dementia to vulnerable veterans secondary to the mental and physical wounds of service.

When the service member is located, the alert is canceled. Nevertheless, their data remains in all the protean forms of media now available. In these searches for service members thought to be lost, there is a risk of violating their privacy if too much protected health information is made widely public. These breaches of confidentiality can further exacerbate the already too prevalent stigmatization of mental illness in the military, which has been a formidable obstacle to persuading those in uniform to seek treatment.¹⁰ As J.R.R. Tolkien has noted, not every person who “wanders” is lost.¹ A veteran may leave his home for some period, even without notifying anyone, without being in grave and imminent danger. The diagnoses we health care professionals assign to patients are wide conceptual nets full of empirical holes: they are poorly predictive and protective mechanisms.¹¹ A broadly written or vague law leaves latitude for bias, discrimination, liability, and fear to drive decisions that to be ethically justifiable require consistency, transparency, equity, and expertise. Much more research is needed to develop situational awareness, scientific accuracy, and clinical reliability to understand when, how, and for whom Green Alerts are genuinely beneficial.

These are not insurmountable questions. The experts and stakeholders appointed to the interagency committee the national Green Alert proposes will work to address these problems. Yet, unless they and we look bravely at the thorny issues these laudable laws present, it will be challenging to achieve their purpose to safeguard the dignity, safety, as well as autonomy and well-being of service members.

A recent article on Medscape entitled “Online Reviews Most Important Factor in Choosing a Doctor: Survey” really got me thinking about my online presence. According to the results of a new Press Ganey survey, online reviews and star ratings are the most important factor for consumers when choosing a new health care provider, even more so than the recommendation of another doctor. Almost 85% of the survey respondents said they wouldn’t make an appointment with a referred provider if they had a rating of less than 4 stars.

To be honest, I’ve rarely thought about my ratings or online reviews, and I almost never enter my own name into a web browser to see what might emerge. I don’t use most popular social media apps, I don’t have a professional website, and I was completely late in joining LinkedIn. After considering the Press Ganey survey results, though, I’m wondering how many patients (or potential patients) have found me online. And what exactly did they see?

So, I just searched online for my ratings and reviews. There weren’t many direct hits (although I’m not sure if that is a good thing or not). One of the results listed me as a “Fibromyalgia Doctor” at www.lymeforums.org. To be clear, I’m a locum tenens infectious diseases provider with a focus on inpatient consultations and teaching. I couldn’t find any reviews for myself on WebMD, but I had one rating on the Healthgrades website – I was pleased to see someone gave me 5 stars (though there weren’t any comments) until I realized the site listed my address at an ob.gyn. office; I’m not even sure if that rating was meant for me.

Use of the Internet to assess my qualities as a physician is clearly limited, and much of the online information about my specialty and practice sites is completely inaccurate. Yet, according to the Press Ganey survey, the average consumer uses three different websites and reads more than five online reviews before making a provider decision. Once they’ve seen a provider, though, patients rank practice customer service and communication as more important than “bedside manner” when considering a 5-star review. So, it appears that many physician reviews and ratings probably reflect the performance of the office staff, not the provider.

Given the few hits that I encountered when searching my own name, I’m not convinced I need to do anything differently about my online presence; essentially, I don’t really have one. However, there were certainly a lot of other physicians with the same last name as mine who did have impressive numbers of reviews and ratings. One doctor of cosmetic surgery had more than 200 reviews on multiple sites; almost all were positive, but a few patients rated him at 1 or 2 (out of 5) stars, suggesting that patients should find a new surgeon. What does one do about those outliers?

Medicine is indeed a business and patients behave as consumers when searching the web for a health care provider. Another survey has suggested that just one negative review may cause a business to risk losing 22% of its customers, and that multiple bad ratings are even worse – nearly 60% of customers will avoid a business with three or more negative online reviews.

A few years ago, The Washington Post published an article about doctors who were fighting back against bad reviews. Unfortunately, while trying to directly combat inaccuracies, some providers divulged sensitive patient information and suffered the consequences of HIPAA violations. Many legal experts suggest that, in most cases, physicians should restrain from responding publicly to negative online reviews, however tempting it may be to react.

If a negative review is attributed to a specific patient, some lawyers recommend contacting them privately by phone to address their concerns; this may clear the air enough to result in a withdrawal of the negative review or rating. Flagging and reporting fake or unsubstantiated negative reviews (or reviews that violate the Terms of Service of a specific platform) can be done. Consultation with an Internet defamation attorney might be helpful in some circumstances, though hopefully, legal action such as a lawsuit or a cease-and-desist letter can be avoided.

For physicians who do maintain an online presence, engaging with an online reputation management service can help suppress fake or negative reviews while offering strategies for building a better reputation. As for me, I think that I’m grateful my name hasn’t attracted a lot of attention at physician ranking and review sites. I guess we’ll see if it stays that way.

Dr. Devlin is president of Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

A recent article on Medscape entitled “Online Reviews Most Important Factor in Choosing a Doctor: Survey” really got me thinking about my online presence. According to the results of a new Press Ganey survey, online reviews and star ratings are the most important factor for consumers when choosing a new health care provider, even more so than the recommendation of another doctor. Almost 85% of the survey respondents said they wouldn’t make an appointment with a referred provider if they had a rating of less than 4 stars.

To be honest, I’ve rarely thought about my ratings or online reviews, and I almost never enter my own name into a web browser to see what might emerge. I don’t use most popular social media apps, I don’t have a professional website, and I was completely late in joining LinkedIn. After considering the Press Ganey survey results, though, I’m wondering how many patients (or potential patients) have found me online. And what exactly did they see?

So, I just searched online for my ratings and reviews. There weren’t many direct hits (although I’m not sure if that is a good thing or not). One of the results listed me as a “Fibromyalgia Doctor” at www.lymeforums.org. To be clear, I’m a locum tenens infectious diseases provider with a focus on inpatient consultations and teaching. I couldn’t find any reviews for myself on WebMD, but I had one rating on the Healthgrades website – I was pleased to see someone gave me 5 stars (though there weren’t any comments) until I realized the site listed my address at an ob.gyn. office; I’m not even sure if that rating was meant for me.

Use of the Internet to assess my qualities as a physician is clearly limited, and much of the online information about my specialty and practice sites is completely inaccurate. Yet, according to the Press Ganey survey, the average consumer uses three different websites and reads more than five online reviews before making a provider decision. Once they’ve seen a provider, though, patients rank practice customer service and communication as more important than “bedside manner” when considering a 5-star review. So, it appears that many physician reviews and ratings probably reflect the performance of the office staff, not the provider.

Given the few hits that I encountered when searching my own name, I’m not convinced I need to do anything differently about my online presence; essentially, I don’t really have one. However, there were certainly a lot of other physicians with the same last name as mine who did have impressive numbers of reviews and ratings. One doctor of cosmetic surgery had more than 200 reviews on multiple sites; almost all were positive, but a few patients rated him at 1 or 2 (out of 5) stars, suggesting that patients should find a new surgeon. What does one do about those outliers?

Medicine is indeed a business and patients behave as consumers when searching the web for a health care provider. Another survey has suggested that just one negative review may cause a business to risk losing 22% of its customers, and that multiple bad ratings are even worse – nearly 60% of customers will avoid a business with three or more negative online reviews.

A few years ago, The Washington Post published an article about doctors who were fighting back against bad reviews. Unfortunately, while trying to directly combat inaccuracies, some providers divulged sensitive patient information and suffered the consequences of HIPAA violations. Many legal experts suggest that, in most cases, physicians should restrain from responding publicly to negative online reviews, however tempting it may be to react.

If a negative review is attributed to a specific patient, some lawyers recommend contacting them privately by phone to address their concerns; this may clear the air enough to result in a withdrawal of the negative review or rating. Flagging and reporting fake or unsubstantiated negative reviews (or reviews that violate the Terms of Service of a specific platform) can be done. Consultation with an Internet defamation attorney might be helpful in some circumstances, though hopefully, legal action such as a lawsuit or a cease-and-desist letter can be avoided.

For physicians who do maintain an online presence, engaging with an online reputation management service can help suppress fake or negative reviews while offering strategies for building a better reputation. As for me, I think that I’m grateful my name hasn’t attracted a lot of attention at physician ranking and review sites. I guess we’ll see if it stays that way.

Dr. Devlin is president of Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

A recent article on Medscape entitled “Online Reviews Most Important Factor in Choosing a Doctor: Survey” really got me thinking about my online presence. According to the results of a new Press Ganey survey, online reviews and star ratings are the most important factor for consumers when choosing a new health care provider, even more so than the recommendation of another doctor. Almost 85% of the survey respondents said they wouldn’t make an appointment with a referred provider if they had a rating of less than 4 stars.

To be honest, I’ve rarely thought about my ratings or online reviews, and I almost never enter my own name into a web browser to see what might emerge. I don’t use most popular social media apps, I don’t have a professional website, and I was completely late in joining LinkedIn. After considering the Press Ganey survey results, though, I’m wondering how many patients (or potential patients) have found me online. And what exactly did they see?

So, I just searched online for my ratings and reviews. There weren’t many direct hits (although I’m not sure if that is a good thing or not). One of the results listed me as a “Fibromyalgia Doctor” at www.lymeforums.org. To be clear, I’m a locum tenens infectious diseases provider with a focus on inpatient consultations and teaching. I couldn’t find any reviews for myself on WebMD, but I had one rating on the Healthgrades website – I was pleased to see someone gave me 5 stars (though there weren’t any comments) until I realized the site listed my address at an ob.gyn. office; I’m not even sure if that rating was meant for me.

Use of the Internet to assess my qualities as a physician is clearly limited, and much of the online information about my specialty and practice sites is completely inaccurate. Yet, according to the Press Ganey survey, the average consumer uses three different websites and reads more than five online reviews before making a provider decision. Once they’ve seen a provider, though, patients rank practice customer service and communication as more important than “bedside manner” when considering a 5-star review. So, it appears that many physician reviews and ratings probably reflect the performance of the office staff, not the provider.

Given the few hits that I encountered when searching my own name, I’m not convinced I need to do anything differently about my online presence; essentially, I don’t really have one. However, there were certainly a lot of other physicians with the same last name as mine who did have impressive numbers of reviews and ratings. One doctor of cosmetic surgery had more than 200 reviews on multiple sites; almost all were positive, but a few patients rated him at 1 or 2 (out of 5) stars, suggesting that patients should find a new surgeon. What does one do about those outliers?

Medicine is indeed a business and patients behave as consumers when searching the web for a health care provider. Another survey has suggested that just one negative review may cause a business to risk losing 22% of its customers, and that multiple bad ratings are even worse – nearly 60% of customers will avoid a business with three or more negative online reviews.

A few years ago, The Washington Post published an article about doctors who were fighting back against bad reviews. Unfortunately, while trying to directly combat inaccuracies, some providers divulged sensitive patient information and suffered the consequences of HIPAA violations. Many legal experts suggest that, in most cases, physicians should restrain from responding publicly to negative online reviews, however tempting it may be to react.

If a negative review is attributed to a specific patient, some lawyers recommend contacting them privately by phone to address their concerns; this may clear the air enough to result in a withdrawal of the negative review or rating. Flagging and reporting fake or unsubstantiated negative reviews (or reviews that violate the Terms of Service of a specific platform) can be done. Consultation with an Internet defamation attorney might be helpful in some circumstances, though hopefully, legal action such as a lawsuit or a cease-and-desist letter can be avoided.

For physicians who do maintain an online presence, engaging with an online reputation management service can help suppress fake or negative reviews while offering strategies for building a better reputation. As for me, I think that I’m grateful my name hasn’t attracted a lot of attention at physician ranking and review sites. I guess we’ll see if it stays that way.

Dr. Devlin is president of Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Eating disorders are among the most prevalent, disabling, and potentially fatal psychiatric illnesses, and the COVID-19 pandemic has exacerbated their burden, with a 15.3% increase in incidence in 2020 compared with previous years.¹ This increase was almost solely among adolescent girls with anorexia nervosa (AN), which is often insidious in onset and more difficult to treat as it advances. Adolescents with AN are most likely to present to their pediatricians, so awareness and early recognition of the symptoms is critical. Pediatricians are also an integral part of the treatment team in AN and can offer monitoring for serious complications, alongside valuable guidance to parents, who are central to treatment and the reestablishment of healthy eating habits in their children. Here we will review the epidemiology, diagnosis, and treatment of anorexia, with an emphasis on what pediatricians need to know to screen and to facilitate treatment.

Epidemiology

AN is marked by a fear of gaining weight or behaviors that interfere with weight gain and a self-evaluation unduly influenced by weight and body shape. Youth with AN often deny the seriousness of their malnutrition, although that is not required for diagnosis. AN can be of a restrictive or binge-purge subtype, and amenorrhea is no longer a requirement for diagnosis. There is not a specific weight or body mass index cutoff for the diagnosis, but the severity of AN is determined by the BMI percentile normed to age and sex. The average age of onset is 18, and the prepandemic prevalence of AN was about 1% of the population. It affects about 10 times as many females as males. It is quite rare prior to puberty, affecting about 0.01% of that age group. There is a heritable component, with a fivefold relative risk in youth with a parent with AN, and twin studies suggest heritability rates as high as 75%. Youth with rigid cognitive styles appear more vulnerable, as do those who participate in activities such as ballet, gymnastics, modeling, and wrestling because of the role of appearance and weight in performance. More than half of patients with AN will have another psychiatric illness, most commonly anxiety disorders, depression, or obsessive-compulsive disorder. AN becomes chronic in up to 15% of sufferers and the mortality rate is close to 10%, with approximately half dying from medical complications and half dying by suicide.

Screening

Parents and pediatricians are usually the first to notice that a child has started to lose weight or is falling off the growth curve. But weight changes usually emerge after feelings of preoccupation with weight, body shape, and body satisfaction. If parents report escalating pickiness around food, increased or compulsive exercise, persistent self-consciousness and self-criticism around weight and body shape, it is worth starting with screening questions.

If you notice preoccupation or anxiety around being weighed, even if the weight or growth curve are still normal, it is worthwhile to screen. Screening questions, such as the SCOFF questionnaire with five simple questions, can be very sensitive for both AN and bulimia nervosa.² There are also many validated screening instruments, such as the Eating Disorder Inventory or Eating Attitudes Test (for adolescents) and the Kids Eating Disorder Survey and the Child Eating Attitudes Test (for younger children), that are short self-reports that you can have your patients fill out when you have a higher index of suspicion. Weight loss or growth failure without a preoccupation around weight or appearance needs a thorough a medical workup, and could be a function of other psychiatric problems, such as depression.

If a child screens positive for an eating disorder, your full physical examination, growth curves, and longitudinal growth charts are critical for diagnosis. Percentile BMIs must be used, given the inaccuracy of standard BMI calculations in this age group. (Centers for Disease Control and Prevention age and sex growth charts include methods for this calculation). Laboratory assessment, including metabolic, kidney, pancreatic, and thyroid function, and an EKG can illuminate if there are consequences of restricting or purging. Of course, you want to evaluate for significant medical symptoms, including bradycardia, orthostasis, and hypokalemia. These medical symptoms are not limited to the severely underweight and merit referral to an emergency department and possible medical admission.

Then, a referral to a clinician who is expert in the assessment and treatment of eating disorders is needed. This may be a child psychiatrist, psychologist, or a colleague pediatrician with this specialization. It is also very important to begin the conversation with the family to introduce your concerns, describe what you have noticed, and discuss the need for further assessment and possibly treatment.

Treatment

Family-based therapy (FBT) is the first-line treatment of shorter-duration AN in children and adolescents. It focuses on the parents, helping them to calmly and effectively manage their child’s eating behaviors until their weight and behaviors have normalized. As a patient’s nutritional status improves, so does cognitive function, emotional flexibility, and mood. Individual therapy and psychopharmacologic treatment can be very effective for comorbid anxiety, mood, attentional, and thought disorders. Family-based work does include the child and is often done in group-based settings with clinicians from multiple disciplines. Dietitians provide education and guidance about healthy nutrition to the child and parents. Therapists may work with the child, parents, or full family to focus on behavior modification and managing distress. Most academic medical centers provide access to FBT, but there are many regions with no providers of this evidence-based treatment. One of the silver linings of the COVID-19 pandemic is that several online services have emerged offering FBT, working with families to manage mealtimes and treatment entirely at home.³ Pediatricians provide regular medical checks to measure progress and help with decisions about when it is safe to permit exercise or advance privileges and independence around eating. Some pediatricians have discovered a deep interest in this area of pediatrics and built their practices on it. Given the surge in prevalence of AN and the needs for adolescent mental health services, we hope more will do so.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Taquet M et al. Br J Psychiatry. 2022;220:262-4.

2. Morgan JF et al. West J Med. 2000 Mar;172(3):164-5.

3. Matheson BE et al. Int J Eat Disord. 2020 Jul;53(7):1142-54.

Eating disorders are among the most prevalent, disabling, and potentially fatal psychiatric illnesses, and the COVID-19 pandemic has exacerbated their burden, with a 15.3% increase in incidence in 2020 compared with previous years.¹ This increase was almost solely among adolescent girls with anorexia nervosa (AN), which is often insidious in onset and more difficult to treat as it advances. Adolescents with AN are most likely to present to their pediatricians, so awareness and early recognition of the symptoms is critical. Pediatricians are also an integral part of the treatment team in AN and can offer monitoring for serious complications, alongside valuable guidance to parents, who are central to treatment and the reestablishment of healthy eating habits in their children. Here we will review the epidemiology, diagnosis, and treatment of anorexia, with an emphasis on what pediatricians need to know to screen and to facilitate treatment.

Epidemiology

AN is marked by a fear of gaining weight or behaviors that interfere with weight gain and a self-evaluation unduly influenced by weight and body shape. Youth with AN often deny the seriousness of their malnutrition, although that is not required for diagnosis. AN can be of a restrictive or binge-purge subtype, and amenorrhea is no longer a requirement for diagnosis. There is not a specific weight or body mass index cutoff for the diagnosis, but the severity of AN is determined by the BMI percentile normed to age and sex. The average age of onset is 18, and the prepandemic prevalence of AN was about 1% of the population. It affects about 10 times as many females as males. It is quite rare prior to puberty, affecting about 0.01% of that age group. There is a heritable component, with a fivefold relative risk in youth with a parent with AN, and twin studies suggest heritability rates as high as 75%. Youth with rigid cognitive styles appear more vulnerable, as do those who participate in activities such as ballet, gymnastics, modeling, and wrestling because of the role of appearance and weight in performance. More than half of patients with AN will have another psychiatric illness, most commonly anxiety disorders, depression, or obsessive-compulsive disorder. AN becomes chronic in up to 15% of sufferers and the mortality rate is close to 10%, with approximately half dying from medical complications and half dying by suicide.

Screening

Parents and pediatricians are usually the first to notice that a child has started to lose weight or is falling off the growth curve. But weight changes usually emerge after feelings of preoccupation with weight, body shape, and body satisfaction. If parents report escalating pickiness around food, increased or compulsive exercise, persistent self-consciousness and self-criticism around weight and body shape, it is worth starting with screening questions.

If you notice preoccupation or anxiety around being weighed, even if the weight or growth curve are still normal, it is worthwhile to screen. Screening questions, such as the SCOFF questionnaire with five simple questions, can be very sensitive for both AN and bulimia nervosa.² There are also many validated screening instruments, such as the Eating Disorder Inventory or Eating Attitudes Test (for adolescents) and the Kids Eating Disorder Survey and the Child Eating Attitudes Test (for younger children), that are short self-reports that you can have your patients fill out when you have a higher index of suspicion. Weight loss or growth failure without a preoccupation around weight or appearance needs a thorough a medical workup, and could be a function of other psychiatric problems, such as depression.

If a child screens positive for an eating disorder, your full physical examination, growth curves, and longitudinal growth charts are critical for diagnosis. Percentile BMIs must be used, given the inaccuracy of standard BMI calculations in this age group. (Centers for Disease Control and Prevention age and sex growth charts include methods for this calculation). Laboratory assessment, including metabolic, kidney, pancreatic, and thyroid function, and an EKG can illuminate if there are consequences of restricting or purging. Of course, you want to evaluate for significant medical symptoms, including bradycardia, orthostasis, and hypokalemia. These medical symptoms are not limited to the severely underweight and merit referral to an emergency department and possible medical admission.

Then, a referral to a clinician who is expert in the assessment and treatment of eating disorders is needed. This may be a child psychiatrist, psychologist, or a colleague pediatrician with this specialization. It is also very important to begin the conversation with the family to introduce your concerns, describe what you have noticed, and discuss the need for further assessment and possibly treatment.

Treatment

Family-based therapy (FBT) is the first-line treatment of shorter-duration AN in children and adolescents. It focuses on the parents, helping them to calmly and effectively manage their child’s eating behaviors until their weight and behaviors have normalized. As a patient’s nutritional status improves, so does cognitive function, emotional flexibility, and mood. Individual therapy and psychopharmacologic treatment can be very effective for comorbid anxiety, mood, attentional, and thought disorders. Family-based work does include the child and is often done in group-based settings with clinicians from multiple disciplines. Dietitians provide education and guidance about healthy nutrition to the child and parents. Therapists may work with the child, parents, or full family to focus on behavior modification and managing distress. Most academic medical centers provide access to FBT, but there are many regions with no providers of this evidence-based treatment. One of the silver linings of the COVID-19 pandemic is that several online services have emerged offering FBT, working with families to manage mealtimes and treatment entirely at home.³ Pediatricians provide regular medical checks to measure progress and help with decisions about when it is safe to permit exercise or advance privileges and independence around eating. Some pediatricians have discovered a deep interest in this area of pediatrics and built their practices on it. Given the surge in prevalence of AN and the needs for adolescent mental health services, we hope more will do so.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Taquet M et al. Br J Psychiatry. 2022;220:262-4.

2. Morgan JF et al. West J Med. 2000 Mar;172(3):164-5.

3. Matheson BE et al. Int J Eat Disord. 2020 Jul;53(7):1142-54.

Eating disorders are among the most prevalent, disabling, and potentially fatal psychiatric illnesses, and the COVID-19 pandemic has exacerbated their burden, with a 15.3% increase in incidence in 2020 compared with previous years.¹ This increase was almost solely among adolescent girls with anorexia nervosa (AN), which is often insidious in onset and more difficult to treat as it advances. Adolescents with AN are most likely to present to their pediatricians, so awareness and early recognition of the symptoms is critical. Pediatricians are also an integral part of the treatment team in AN and can offer monitoring for serious complications, alongside valuable guidance to parents, who are central to treatment and the reestablishment of healthy eating habits in their children. Here we will review the epidemiology, diagnosis, and treatment of anorexia, with an emphasis on what pediatricians need to know to screen and to facilitate treatment.

Epidemiology

AN is marked by a fear of gaining weight or behaviors that interfere with weight gain and a self-evaluation unduly influenced by weight and body shape. Youth with AN often deny the seriousness of their malnutrition, although that is not required for diagnosis. AN can be of a restrictive or binge-purge subtype, and amenorrhea is no longer a requirement for diagnosis. There is not a specific weight or body mass index cutoff for the diagnosis, but the severity of AN is determined by the BMI percentile normed to age and sex. The average age of onset is 18, and the prepandemic prevalence of AN was about 1% of the population. It affects about 10 times as many females as males. It is quite rare prior to puberty, affecting about 0.01% of that age group. There is a heritable component, with a fivefold relative risk in youth with a parent with AN, and twin studies suggest heritability rates as high as 75%. Youth with rigid cognitive styles appear more vulnerable, as do those who participate in activities such as ballet, gymnastics, modeling, and wrestling because of the role of appearance and weight in performance. More than half of patients with AN will have another psychiatric illness, most commonly anxiety disorders, depression, or obsessive-compulsive disorder. AN becomes chronic in up to 15% of sufferers and the mortality rate is close to 10%, with approximately half dying from medical complications and half dying by suicide.

Screening

Parents and pediatricians are usually the first to notice that a child has started to lose weight or is falling off the growth curve. But weight changes usually emerge after feelings of preoccupation with weight, body shape, and body satisfaction. If parents report escalating pickiness around food, increased or compulsive exercise, persistent self-consciousness and self-criticism around weight and body shape, it is worth starting with screening questions.

If you notice preoccupation or anxiety around being weighed, even if the weight or growth curve are still normal, it is worthwhile to screen. Screening questions, such as the SCOFF questionnaire with five simple questions, can be very sensitive for both AN and bulimia nervosa.² There are also many validated screening instruments, such as the Eating Disorder Inventory or Eating Attitudes Test (for adolescents) and the Kids Eating Disorder Survey and the Child Eating Attitudes Test (for younger children), that are short self-reports that you can have your patients fill out when you have a higher index of suspicion. Weight loss or growth failure without a preoccupation around weight or appearance needs a thorough a medical workup, and could be a function of other psychiatric problems, such as depression.

If a child screens positive for an eating disorder, your full physical examination, growth curves, and longitudinal growth charts are critical for diagnosis. Percentile BMIs must be used, given the inaccuracy of standard BMI calculations in this age group. (Centers for Disease Control and Prevention age and sex growth charts include methods for this calculation). Laboratory assessment, including metabolic, kidney, pancreatic, and thyroid function, and an EKG can illuminate if there are consequences of restricting or purging. Of course, you want to evaluate for significant medical symptoms, including bradycardia, orthostasis, and hypokalemia. These medical symptoms are not limited to the severely underweight and merit referral to an emergency department and possible medical admission.

Then, a referral to a clinician who is expert in the assessment and treatment of eating disorders is needed. This may be a child psychiatrist, psychologist, or a colleague pediatrician with this specialization. It is also very important to begin the conversation with the family to introduce your concerns, describe what you have noticed, and discuss the need for further assessment and possibly treatment.

Treatment

Family-based therapy (FBT) is the first-line treatment of shorter-duration AN in children and adolescents. It focuses on the parents, helping them to calmly and effectively manage their child’s eating behaviors until their weight and behaviors have normalized. As a patient’s nutritional status improves, so does cognitive function, emotional flexibility, and mood. Individual therapy and psychopharmacologic treatment can be very effective for comorbid anxiety, mood, attentional, and thought disorders. Family-based work does include the child and is often done in group-based settings with clinicians from multiple disciplines. Dietitians provide education and guidance about healthy nutrition to the child and parents. Therapists may work with the child, parents, or full family to focus on behavior modification and managing distress. Most academic medical centers provide access to FBT, but there are many regions with no providers of this evidence-based treatment. One of the silver linings of the COVID-19 pandemic is that several online services have emerged offering FBT, working with families to manage mealtimes and treatment entirely at home.³ Pediatricians provide regular medical checks to measure progress and help with decisions about when it is safe to permit exercise or advance privileges and independence around eating. Some pediatricians have discovered a deep interest in this area of pediatrics and built their practices on it. Given the surge in prevalence of AN and the needs for adolescent mental health services, we hope more will do so.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

References

1. Taquet M et al. Br J Psychiatry. 2022;220:262-4.

2. Morgan JF et al. West J Med. 2000 Mar;172(3):164-5.

3. Matheson BE et al. Int J Eat Disord. 2020 Jul;53(7):1142-54.

You have an appointment with a 14-year-old youth you last saw for an annual camp physical. He had screened positive for depression, and you had referred him to a local therapist. He did not have an appointment until after camp, and you have only met a few times, but since you had spoken with him about his depression, he set up an appointment with you to ask about medications. When you meet him you ask about what he had been doing in therapy and he says, “I’m learning ‘coping skills,’ but they don’t work.”

From breathing exercises and sticker charts to mindfulness and grounding exercise, coping skills can be crucial for learning how to manage distress, regulate emotions, become more effective interpersonally, and function better. Similarly, parenting interventions, which change the way parents and youth interact, are a central family intervention for behavioral problems in youth.

It is very common, however, to hear that they “don’t work” or have a parent say, “We tried that, it doesn’t work.”

When kids and parents reject coping skills and behavioral interventions by saying they do not work, the consequences can be substantial. It can mean the rejection of coping skills and strategies that actually would have helped, given time and support; that kids and families bounce between services with increasing frustration; that they search for a magic bullet (which also won’t work); and, particularly concerning for physicians, a belief that the youth have not received the right medication, resulting in potentially unhelpful concoctions of medication.

One of the biggest challenges in helping youth and parents overcome their difficulties – whether these difficulties are depression and anxiety or being better parents to struggling kids – is helping them understand that despite the fact that coping skills and behavioral interventions do not seem to work, they work.

We just have to do a better job explaining what that “work” is.

There are five points you can make.

• First, the coping skill or behavioral intervention is not supposed to work if that means solving the underlying problem. Coping skills and behavioral interventions do not immediately cure anxiety, mend broken hearts, correct disruptive behaviors, disentangle power struggles, or alleviate depression. That is not what their job is. Coping skills and behavioral interventions are there to help us get better at handling complex situations and feelings. In particular, they are good at helping us manage our thoughts (“I can’t do it,” “He should behave better”) and our affect (anger, frustration, rage, anxiety, sadness), so that over time we get better at solving the problems, and break out of the patterns that perpetuate these problems.
• Second, kids and parents do not give skills credit for when they do work. That time you were spiraling out of control and told your mom you needed a break and watched some YouTube videos and then joined the family for dinner? Your coping skills worked, but nobody noticed because they worked. We need to help our young patients and families identify those times that coping skills and behavioral interventions worked.
• Third, let’s face it: Nothing works all the time. It is no wonder kids and families are disappointed by coping skills and behavioral interventions if they think they magically work once and forever. We need to manage expectations.
• Fourth, we know they are supposed to fail, and we should discuss this openly up front. This may sound surprising, but challenging behaviors often get worse when we begin to work on them. “Extinction bursts” is probably the easiest explanation, but for psychodynamically oriented youth and families we could talk about “resistance.” No matter what, things tend to get worse before they get better. We should let people know this ahead of time.
• Fifth, and this is the one that forces youth and parents to ask how hard they actually tried, these skills need to be practiced. You can’t be in the middle of a panic attack and for the first time start trying to pace your breathing with a technique a therapist told you about 3 weeks ago. This makes about as much sense as not training for a marathon. You need to practice and build up the skills, recognizing that as you become more familiar with them, they will help you manage during stressful situations. Every skill should be practiced, preferably several times or more in sessions, maybe every session, and definitely outside of sessions when not in distress.

We cannot blame children and parents for thinking that coping skills and behavioral interventions do not work. They are struggling, suffering, fighting, frightened, angry, anxious, frustrated, and often desperate for something to make everything better. Helping them recognize this desire for things to be better while managing expectations is an essential complement to supporting the use of coping skills and behavioral interventions, and a fairly easy conversation to have with youth.

So when you are talking about coping skills and parental behavioral interventions, it is important to be prepared for the “it didn’t work” conversation, and even to address these issues up front. After all, these strategies may not solve all the problems in the world, but can be lifelong ways of coping with life’s challenges.
 

Dr. Henderson is associate professor of clinical psychiatry at New York University and deputy director of child and adolescent psychiatry at Bellevue Hospital, New York.

You have an appointment with a 14-year-old youth you last saw for an annual camp physical. He had screened positive for depression, and you had referred him to a local therapist. He did not have an appointment until after camp, and you have only met a few times, but since you had spoken with him about his depression, he set up an appointment with you to ask about medications. When you meet him you ask about what he had been doing in therapy and he says, “I’m learning ‘coping skills,’ but they don’t work.”

From breathing exercises and sticker charts to mindfulness and grounding exercise, coping skills can be crucial for learning how to manage distress, regulate emotions, become more effective interpersonally, and function better. Similarly, parenting interventions, which change the way parents and youth interact, are a central family intervention for behavioral problems in youth.

It is very common, however, to hear that they “don’t work” or have a parent say, “We tried that, it doesn’t work.”

When kids and parents reject coping skills and behavioral interventions by saying they do not work, the consequences can be substantial. It can mean the rejection of coping skills and strategies that actually would have helped, given time and support; that kids and families bounce between services with increasing frustration; that they search for a magic bullet (which also won’t work); and, particularly concerning for physicians, a belief that the youth have not received the right medication, resulting in potentially unhelpful concoctions of medication.

One of the biggest challenges in helping youth and parents overcome their difficulties – whether these difficulties are depression and anxiety or being better parents to struggling kids – is helping them understand that despite the fact that coping skills and behavioral interventions do not seem to work, they work.

We just have to do a better job explaining what that “work” is.

There are five points you can make.

• First, the coping skill or behavioral intervention is not supposed to work if that means solving the underlying problem. Coping skills and behavioral interventions do not immediately cure anxiety, mend broken hearts, correct disruptive behaviors, disentangle power struggles, or alleviate depression. That is not what their job is. Coping skills and behavioral interventions are there to help us get better at handling complex situations and feelings. In particular, they are good at helping us manage our thoughts (“I can’t do it,” “He should behave better”) and our affect (anger, frustration, rage, anxiety, sadness), so that over time we get better at solving the problems, and break out of the patterns that perpetuate these problems.
• Second, kids and parents do not give skills credit for when they do work. That time you were spiraling out of control and told your mom you needed a break and watched some YouTube videos and then joined the family for dinner? Your coping skills worked, but nobody noticed because they worked. We need to help our young patients and families identify those times that coping skills and behavioral interventions worked.
• Third, let’s face it: Nothing works all the time. It is no wonder kids and families are disappointed by coping skills and behavioral interventions if they think they magically work once and forever. We need to manage expectations.
• Fourth, we know they are supposed to fail, and we should discuss this openly up front. This may sound surprising, but challenging behaviors often get worse when we begin to work on them. “Extinction bursts” is probably the easiest explanation, but for psychodynamically oriented youth and families we could talk about “resistance.” No matter what, things tend to get worse before they get better. We should let people know this ahead of time.
• Fifth, and this is the one that forces youth and parents to ask how hard they actually tried, these skills need to be practiced. You can’t be in the middle of a panic attack and for the first time start trying to pace your breathing with a technique a therapist told you about 3 weeks ago. This makes about as much sense as not training for a marathon. You need to practice and build up the skills, recognizing that as you become more familiar with them, they will help you manage during stressful situations. Every skill should be practiced, preferably several times or more in sessions, maybe every session, and definitely outside of sessions when not in distress.

We cannot blame children and parents for thinking that coping skills and behavioral interventions do not work. They are struggling, suffering, fighting, frightened, angry, anxious, frustrated, and often desperate for something to make everything better. Helping them recognize this desire for things to be better while managing expectations is an essential complement to supporting the use of coping skills and behavioral interventions, and a fairly easy conversation to have with youth.

So when you are talking about coping skills and parental behavioral interventions, it is important to be prepared for the “it didn’t work” conversation, and even to address these issues up front. After all, these strategies may not solve all the problems in the world, but can be lifelong ways of coping with life’s challenges.
 

Dr. Henderson is associate professor of clinical psychiatry at New York University and deputy director of child and adolescent psychiatry at Bellevue Hospital, New York.

You have an appointment with a 14-year-old youth you last saw for an annual camp physical. He had screened positive for depression, and you had referred him to a local therapist. He did not have an appointment until after camp, and you have only met a few times, but since you had spoken with him about his depression, he set up an appointment with you to ask about medications. When you meet him you ask about what he had been doing in therapy and he says, “I’m learning ‘coping skills,’ but they don’t work.”

From breathing exercises and sticker charts to mindfulness and grounding exercise, coping skills can be crucial for learning how to manage distress, regulate emotions, become more effective interpersonally, and function better. Similarly, parenting interventions, which change the way parents and youth interact, are a central family intervention for behavioral problems in youth.

It is very common, however, to hear that they “don’t work” or have a parent say, “We tried that, it doesn’t work.”

When kids and parents reject coping skills and behavioral interventions by saying they do not work, the consequences can be substantial. It can mean the rejection of coping skills and strategies that actually would have helped, given time and support; that kids and families bounce between services with increasing frustration; that they search for a magic bullet (which also won’t work); and, particularly concerning for physicians, a belief that the youth have not received the right medication, resulting in potentially unhelpful concoctions of medication.

One of the biggest challenges in helping youth and parents overcome their difficulties – whether these difficulties are depression and anxiety or being better parents to struggling kids – is helping them understand that despite the fact that coping skills and behavioral interventions do not seem to work, they work.

We just have to do a better job explaining what that “work” is.

There are five points you can make.

• First, the coping skill or behavioral intervention is not supposed to work if that means solving the underlying problem. Coping skills and behavioral interventions do not immediately cure anxiety, mend broken hearts, correct disruptive behaviors, disentangle power struggles, or alleviate depression. That is not what their job is. Coping skills and behavioral interventions are there to help us get better at handling complex situations and feelings. In particular, they are good at helping us manage our thoughts (“I can’t do it,” “He should behave better”) and our affect (anger, frustration, rage, anxiety, sadness), so that over time we get better at solving the problems, and break out of the patterns that perpetuate these problems.
• Second, kids and parents do not give skills credit for when they do work. That time you were spiraling out of control and told your mom you needed a break and watched some YouTube videos and then joined the family for dinner? Your coping skills worked, but nobody noticed because they worked. We need to help our young patients and families identify those times that coping skills and behavioral interventions worked.
• Third, let’s face it: Nothing works all the time. It is no wonder kids and families are disappointed by coping skills and behavioral interventions if they think they magically work once and forever. We need to manage expectations.
• Fourth, we know they are supposed to fail, and we should discuss this openly up front. This may sound surprising, but challenging behaviors often get worse when we begin to work on them. “Extinction bursts” is probably the easiest explanation, but for psychodynamically oriented youth and families we could talk about “resistance.” No matter what, things tend to get worse before they get better. We should let people know this ahead of time.
• Fifth, and this is the one that forces youth and parents to ask how hard they actually tried, these skills need to be practiced. You can’t be in the middle of a panic attack and for the first time start trying to pace your breathing with a technique a therapist told you about 3 weeks ago. This makes about as much sense as not training for a marathon. You need to practice and build up the skills, recognizing that as you become more familiar with them, they will help you manage during stressful situations. Every skill should be practiced, preferably several times or more in sessions, maybe every session, and definitely outside of sessions when not in distress.

We cannot blame children and parents for thinking that coping skills and behavioral interventions do not work. They are struggling, suffering, fighting, frightened, angry, anxious, frustrated, and often desperate for something to make everything better. Helping them recognize this desire for things to be better while managing expectations is an essential complement to supporting the use of coping skills and behavioral interventions, and a fairly easy conversation to have with youth.

So when you are talking about coping skills and parental behavioral interventions, it is important to be prepared for the “it didn’t work” conversation, and even to address these issues up front. After all, these strategies may not solve all the problems in the world, but can be lifelong ways of coping with life’s challenges.
 

Dr. Henderson is associate professor of clinical psychiatry at New York University and deputy director of child and adolescent psychiatry at Bellevue Hospital, New York.

Recently, I encountered a study in Pediatrics that hoped to answer the question of whether there was any benefit to tactile stimulation in those nerve-rattling moments when a newborn didn’t seem to take much interest in breathing: “Tactile stimulation in newborn infants with inadequate respiration at birth: A systematic review.” Now there is a title that grabs the attention of every frontline pediatrician who has sweated through those minutes that seemed like hours in the delivery room when some little rascal has decided that breathing isn’t a priority.

Of course, your great grandmother and everyone else knew what needed to be done – the obstetrician hung the baby by his or her ankles and slapped it on the bottom a couple of times. But you went to medical school and learned that was barbaric. Instead, you modeled the behavior of the residents and delivery room nurses who had more refined techniques such as heel flicking and vigorous spine rubbing. You never thought to ask if there was any science behind those activities because everyone did them.

Well, the authors of the article in Pediatrics, writing on behalf of the International Liaison Committee on Resuscitation and Neonatal Life Support Task Force, thought the time had come to turn over a few stones and see if tactile stimulation was a benefit in resuscitation. Beginning with 2,455 possibly relevant articles, they quickly (I suspect they would quibble with the “quickly” part) winnowed these down to two observational studies, one of which was rejected because of “critical risk of bias.” The surviving study showed a reduction in tracheal intubation in infants who had received tactile stimulation. However, the authors felt that the “certainty of evidence was very low.”

So, there you have it. Aren’t you glad you didn’t invest 15 or 20 minutes discovering what you probably had guessed already? You can thank me later.

You already suspected that it may not help. However, like any good physician, what you really wanted to know is whether were you doing any harm by heel flicking and spine rubbing. And I bet you already had an opinion about the answer to that question. During your training, you may have seen delivery room personnel who were clearly too vigorous in their tactile stimulation and/or too persistent in their heel flicking and spine rubbing when the next steps in resuscitation needed to be taken. That’s the next study that needs to be done. I hope that study finds that tactile stimulation may not help but as long as it is done using specific techniques and within certain temporal parameters it does no harm.

I was never much for heel flicking. My favorite tactile stimulation was encircling the pokey infant’s chest in my hand, gently compressing and then quickly releasing a couple of times. My hope was that by mimicking the birth process the sensors in the infant’s chest wall would remind him it was time to breathe. That, and a silent plea to Mother Nature, worked most of the time.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Recently, I encountered a study in Pediatrics that hoped to answer the question of whether there was any benefit to tactile stimulation in those nerve-rattling moments when a newborn didn’t seem to take much interest in breathing: “Tactile stimulation in newborn infants with inadequate respiration at birth: A systematic review.” Now there is a title that grabs the attention of every frontline pediatrician who has sweated through those minutes that seemed like hours in the delivery room when some little rascal has decided that breathing isn’t a priority.

Of course, your great grandmother and everyone else knew what needed to be done – the obstetrician hung the baby by his or her ankles and slapped it on the bottom a couple of times. But you went to medical school and learned that was barbaric. Instead, you modeled the behavior of the residents and delivery room nurses who had more refined techniques such as heel flicking and vigorous spine rubbing. You never thought to ask if there was any science behind those activities because everyone did them.

Well, the authors of the article in Pediatrics, writing on behalf of the International Liaison Committee on Resuscitation and Neonatal Life Support Task Force, thought the time had come to turn over a few stones and see if tactile stimulation was a benefit in resuscitation. Beginning with 2,455 possibly relevant articles, they quickly (I suspect they would quibble with the “quickly” part) winnowed these down to two observational studies, one of which was rejected because of “critical risk of bias.” The surviving study showed a reduction in tracheal intubation in infants who had received tactile stimulation. However, the authors felt that the “certainty of evidence was very low.”

So, there you have it. Aren’t you glad you didn’t invest 15 or 20 minutes discovering what you probably had guessed already? You can thank me later.

You already suspected that it may not help. However, like any good physician, what you really wanted to know is whether were you doing any harm by heel flicking and spine rubbing. And I bet you already had an opinion about the answer to that question. During your training, you may have seen delivery room personnel who were clearly too vigorous in their tactile stimulation and/or too persistent in their heel flicking and spine rubbing when the next steps in resuscitation needed to be taken. That’s the next study that needs to be done. I hope that study finds that tactile stimulation may not help but as long as it is done using specific techniques and within certain temporal parameters it does no harm.

I was never much for heel flicking. My favorite tactile stimulation was encircling the pokey infant’s chest in my hand, gently compressing and then quickly releasing a couple of times. My hope was that by mimicking the birth process the sensors in the infant’s chest wall would remind him it was time to breathe. That, and a silent plea to Mother Nature, worked most of the time.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Recently, I encountered a study in Pediatrics that hoped to answer the question of whether there was any benefit to tactile stimulation in those nerve-rattling moments when a newborn didn’t seem to take much interest in breathing: “Tactile stimulation in newborn infants with inadequate respiration at birth: A systematic review.” Now there is a title that grabs the attention of every frontline pediatrician who has sweated through those minutes that seemed like hours in the delivery room when some little rascal has decided that breathing isn’t a priority.

Of course, your great grandmother and everyone else knew what needed to be done – the obstetrician hung the baby by his or her ankles and slapped it on the bottom a couple of times. But you went to medical school and learned that was barbaric. Instead, you modeled the behavior of the residents and delivery room nurses who had more refined techniques such as heel flicking and vigorous spine rubbing. You never thought to ask if there was any science behind those activities because everyone did them.

Well, the authors of the article in Pediatrics, writing on behalf of the International Liaison Committee on Resuscitation and Neonatal Life Support Task Force, thought the time had come to turn over a few stones and see if tactile stimulation was a benefit in resuscitation. Beginning with 2,455 possibly relevant articles, they quickly (I suspect they would quibble with the “quickly” part) winnowed these down to two observational studies, one of which was rejected because of “critical risk of bias.” The surviving study showed a reduction in tracheal intubation in infants who had received tactile stimulation. However, the authors felt that the “certainty of evidence was very low.”

So, there you have it. Aren’t you glad you didn’t invest 15 or 20 minutes discovering what you probably had guessed already? You can thank me later.

You already suspected that it may not help. However, like any good physician, what you really wanted to know is whether were you doing any harm by heel flicking and spine rubbing. And I bet you already had an opinion about the answer to that question. During your training, you may have seen delivery room personnel who were clearly too vigorous in their tactile stimulation and/or too persistent in their heel flicking and spine rubbing when the next steps in resuscitation needed to be taken. That’s the next study that needs to be done. I hope that study finds that tactile stimulation may not help but as long as it is done using specific techniques and within certain temporal parameters it does no harm.

I was never much for heel flicking. My favorite tactile stimulation was encircling the pokey infant’s chest in my hand, gently compressing and then quickly releasing a couple of times. My hope was that by mimicking the birth process the sensors in the infant’s chest wall would remind him it was time to breathe. That, and a silent plea to Mother Nature, worked most of the time.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

I believe that the most important recommendation from the American Heart Association in recent years is to confirm office blood pressure (BP) readings with repeated home BP measurements, for both diagnosis and management of hypertension. Office BPs are notoriously inaccurate, because it is exceedingly difficult to measure BP properly in a busy office setting. Even when measured correctly, the office BP does not accurately reflect a person’s BP throughout the day, which is the best predictor of cardiovascular damage from hypertension.

Office BPs are notoriously inaccurate, because it is exceedingly difficult to measure BP properly in a busy office setting.

Among the problems with relying on office BP readings:We would treat many people for hypertension who are not hypertensive, because 15% to 30% of those with elevated office BP readings have “white-coat” hypertension, which does not require medication.¹ White-coat hypertension can only be diagnosed with home BP readings or 24-hour ambulatory BP monitoring.

We would miss the diagnosis of hypertension in patients with “masked” hypertension—that is, people who have normal BP in the office but elevated ambulatory BP. It is estimated that 12% of US adults have masked hypertension.²

We would overtreat some patients who have hypertension and undertreat others, since office BP measurements can underestimate BP by an average of 24/14 mm Hg and overestimate BP by an average of 33/23 mm Hg.³

In this issue of JFP, Spaulding and colleagues⁴ provide an extensive summary of the research that supports the recommendation for home BP measurements. Here are 3 key takeaways:

1. Use an automated BP monitor to measure BP in the office. Automated BP monitors that take repeated BPs over the course of about 5 minutes and average the results provide a much better estimate of 24-hour BP. It is worth the extra time and may be the only basis for making decisions about medications if a patient is unwilling or unable to take home BP readings.
2. Provide training to patients who are willing to monitor their BP at home. Explain how to take their BP properly and instruct them to record at least 12 readings over the course of 3 days prior to office visits.
3. Recommend patients use a validated BP monitor that uses the brachial artery for measurement, not the wrist (visit www.stridebp.org/bp-monitors and choose “Home”).

I believe that the most important recommendation from the American Heart Association in recent years is to confirm office blood pressure (BP) readings with repeated home BP measurements, for both diagnosis and management of hypertension. Office BPs are notoriously inaccurate, because it is exceedingly difficult to measure BP properly in a busy office setting. Even when measured correctly, the office BP does not accurately reflect a person’s BP throughout the day, which is the best predictor of cardiovascular damage from hypertension.

Office BPs are notoriously inaccurate, because it is exceedingly difficult to measure BP properly in a busy office setting.

Among the problems with relying on office BP readings:We would treat many people for hypertension who are not hypertensive, because 15% to 30% of those with elevated office BP readings have “white-coat” hypertension, which does not require medication.¹ White-coat hypertension can only be diagnosed with home BP readings or 24-hour ambulatory BP monitoring.

We would miss the diagnosis of hypertension in patients with “masked” hypertension—that is, people who have normal BP in the office but elevated ambulatory BP. It is estimated that 12% of US adults have masked hypertension.²

We would overtreat some patients who have hypertension and undertreat others, since office BP measurements can underestimate BP by an average of 24/14 mm Hg and overestimate BP by an average of 33/23 mm Hg.³

In this issue of JFP, Spaulding and colleagues⁴ provide an extensive summary of the research that supports the recommendation for home BP measurements. Here are 3 key takeaways:

1. Use an automated BP monitor to measure BP in the office. Automated BP monitors that take repeated BPs over the course of about 5 minutes and average the results provide a much better estimate of 24-hour BP. It is worth the extra time and may be the only basis for making decisions about medications if a patient is unwilling or unable to take home BP readings.
2. Provide training to patients who are willing to monitor their BP at home. Explain how to take their BP properly and instruct them to record at least 12 readings over the course of 3 days prior to office visits.
3. Recommend patients use a validated BP monitor that uses the brachial artery for measurement, not the wrist (visit www.stridebp.org/bp-monitors and choose “Home”).

I believe that the most important recommendation from the American Heart Association in recent years is to confirm office blood pressure (BP) readings with repeated home BP measurements, for both diagnosis and management of hypertension. Office BPs are notoriously inaccurate, because it is exceedingly difficult to measure BP properly in a busy office setting. Even when measured correctly, the office BP does not accurately reflect a person’s BP throughout the day, which is the best predictor of cardiovascular damage from hypertension.

Office BPs are notoriously inaccurate, because it is exceedingly difficult to measure BP properly in a busy office setting.

Among the problems with relying on office BP readings:We would treat many people for hypertension who are not hypertensive, because 15% to 30% of those with elevated office BP readings have “white-coat” hypertension, which does not require medication.¹ White-coat hypertension can only be diagnosed with home BP readings or 24-hour ambulatory BP monitoring.

We would miss the diagnosis of hypertension in patients with “masked” hypertension—that is, people who have normal BP in the office but elevated ambulatory BP. It is estimated that 12% of US adults have masked hypertension.²

We would overtreat some patients who have hypertension and undertreat others, since office BP measurements can underestimate BP by an average of 24/14 mm Hg and overestimate BP by an average of 33/23 mm Hg.³

In this issue of JFP, Spaulding and colleagues⁴ provide an extensive summary of the research that supports the recommendation for home BP measurements. Here are 3 key takeaways:

1. Use an automated BP monitor to measure BP in the office. Automated BP monitors that take repeated BPs over the course of about 5 minutes and average the results provide a much better estimate of 24-hour BP. It is worth the extra time and may be the only basis for making decisions about medications if a patient is unwilling or unable to take home BP readings.
2. Provide training to patients who are willing to monitor their BP at home. Explain how to take their BP properly and instruct them to record at least 12 readings over the course of 3 days prior to office visits.
3. Recommend patients use a validated BP monitor that uses the brachial artery for measurement, not the wrist (visit www.stridebp.org/bp-monitors and choose “Home”).

This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.

To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
 

Tracing the outbreak in the United States

How has this outbreak played out thus far in the United States, and what have we learned from that?

Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.

Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).

By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.

Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.

Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.

The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
 

European and global cases

What has been the experience with this in Europe and elsewhere globally?

In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.

Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.

On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.

What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?

In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.

The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.

The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.

Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?

Not to my knowledge.
 

What clinicians need to know

What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?

It may be a collective heightened concern following the emergence of COVID.

Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.

Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?

An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.

In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.

Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.

Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?

Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.

In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.

What do hepatologists need to be doing when presented with suspected cases?

The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.

In addition, it is prudent to check for SARS-CoV-2 by PCR.

What are the major questions that remain and that you’d like to see elucidated going forward?

There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?

Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

A version of this article first appeared on Medscape.com.

This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.

To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
 

Tracing the outbreak in the United States

How has this outbreak played out thus far in the United States, and what have we learned from that?

Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.

Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).

By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.

Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.

Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.

The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
 

European and global cases

What has been the experience with this in Europe and elsewhere globally?

In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.

Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.

On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.

What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?

In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.

The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.

The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.

Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?

Not to my knowledge.
 

What clinicians need to know

What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?

It may be a collective heightened concern following the emergence of COVID.

Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.

Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?

An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.

In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.

Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.

Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?

Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.

In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.

What do hepatologists need to be doing when presented with suspected cases?

The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.

In addition, it is prudent to check for SARS-CoV-2 by PCR.

What are the major questions that remain and that you’d like to see elucidated going forward?

There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?

Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

A version of this article first appeared on Medscape.com.

This spring, global health advisories have been issued regarding an alarming – and as-yet unexplained – uptick of hepatitis in children. Currently, over 200 cases have been reported worldwide, a relatively small amount that nonetheless belies a considerable toll, including several deaths and the need for liver transplantation in a number of patients. The long-term implications are not yet known. Global health officials are working hard to determine a cause, with many focusing on the underlying cases of adenovirus that several patients have presented with.

To understand more, this news organization reached out to frequent contributor William F. Balistreri, MD, a specialist in pediatric gastroenterology and hepatology at Cincinnati Children’s Hospital Medical Center, where to date they have treated at least six cases of hepatitis in otherwise healthy young children, with one requiring a liver transplant. Dr. Balistreri discussed how the outbreak has developed to date, his advice to hepatologists and pediatricians, and where we stand now in this fast-evolving crisis.
 

Tracing the outbreak in the United States

How has this outbreak played out thus far in the United States, and what have we learned from that?

Sporadic reports of cases in multiple states are appearing. On April 21, 2022, a health alert was issued by the Centers for Disease Control and Prevention, recommending testing for adenovirus in children with acute hepatitis of an unknown etiology.

Baker and colleagues recently described five children with severe hepatitis and adenovirus viremia who were admitted to a children’s hospital in Birmingham, Ala., between October and November 2021. In collaboration with local and state officials, the CDC reviewed clinical records in order to identify patients with hepatitis and concomitant adenovirus infection, confirmed by polymerase chain reaction (PCR).

By February 2022, a total of nine children were identified. There was no epidemiologic linkage among these nine patients; all were well and immunocompetent. The prodromal features were somewhat similar: upper respiratory infection, vomiting, diarrhea, and jaundice. All children had markedly elevated aminotransferase levels and variably elevated total bilirubin levels. Extensive workup for other causes of acute liver injury (for example, other viruses, toxins/drugs, metabolic and autoimmune diseases) was unrevealing.

Specifically, none had documented SARS-CoV-2 infection. However, in all nine children, adenovirus was detected in whole blood samples. In the six children who underwent liver biopsy, there was nonspecific hepatitis, without inclusions or immunohistochemical detection of viral agents, including adenovirus. In three patients, the liver injury progressed, and despite the administration of antiviral agents, two underwent liver transplantation.

Baker and colleagues also suggested that measurement of adenovirus titers in whole blood (rather than plasma) may be more sensitive.

The CDC has recommended monitoring and surveillance in order to more fully understand the nature of the illness.
 

European and global cases

What has been the experience with this in Europe and elsewhere globally?

In mid-to-late 2021, several cases of acute hepatitis of unknown nature in children were identified in Europe. Public health officials in the United Kingdom investigated the high number of cases seen in children from England, Scotland, and Wales. They noted approximately 60 cases in England, mostly in children aged 2-5 years.

Marsh and colleagues reported a cluster of cases of severe hepatitis of unknown origin in Scotland affecting children aged 3-5 years. In Scotland, admitted cases were routinely tested for SARS-CoV-2. Of the 13 cases, five had a recent positive test. They discussed the possibility of increased severity of disease following infection with Omicron BA.2 (the dominant SARS-CoV-2 virus circulating in Scotland at that time) or infection by an uncharacterized SARS-CoV-2 variant. None of the children had been vaccinated for SARS-CoV-2.

On April 15, 2022, the World Health Organization Disease Outbreak News published a report of acute hepatitis of unknown etiology occurring in Great Britain and Northern Ireland. By April 21, 2022, 169 cases of acute hepatitis of unknown origin in children younger than 16 years had been reported from 11 countries in the WHO European region and 1 country in the WHO region of the Americas. Approximately 10% required a liver transplantation and at least one death was reported.

What has been established about the possible connection to the SARS-CoV-2 virus, particularly as it relates to coinfection with adenovirus?

In that WHO report of 169 cases, adenovirus was detected in 74 and SARS-CoV-2 in 20. Of note, 19 cases had a SARS-CoV-2 and adenovirus coinfection.

The report’s authors emphasized that, “while adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.” The authors questioned whether this represents a continuing increase in cases of hepatitis or reflects an increased awareness.

The stated priority of the WHO is to determine the cause and to further refine control and prevention actions.

Given the worldwide nature of this outbreak, have connections between any of the cases been made yet?

Not to my knowledge.
 

What clinicians need to know

What makes this outbreak of hepatitis cases particularly concerning to the health care community, in comparison to other childhood diseases that occur globally? Is it because the cause is unknown or is it for other reasons?

It may be a collective heightened concern following the emergence of COVID.

Whether it represents a new form of acute hepatitis, a continuing increase in cases of hepatitis, or an increased awareness because of the well-publicized alerts remains to be determined. We certainly saw “viral-induced hepatitis” in the past.

Young patients may first be brought to pediatricians. What, if anything, should pediatricians be on the lookout for? Do they need a heightened index of suspicion or are the cases too rare at this point?

An awareness of the “outbreak” may allow the clinician to extend the typical workup of a child presenting with an undefined, presumably viral illness.

In the cases reported, the prodromal and/or presenting symptoms were respiratory and gastrointestinal in nature. They include nausea, vomiting, diarrhea, and abdominal pain.

Specifically, if jaundice and/or scleral icterus is noted, then hepatitis should be suspected.

Should pediatricians consider early referral to a pediatric gastroenterologist or hepatologist?

Yes, because there is the potential for finding a treatable cause (for example, autoimmune hepatitis or a specific metabolic disease) in a patient presenting in this fashion.

In addition, the potential for progression to acute liver failure (with coagulopathy and encephalopathy), albeit rare, exists.

What do hepatologists need to be doing when presented with suspected cases?

The typical clinical picture holds and the workup is standard. The one new key, given the recent data, is to test for adenovirus, using whole blood versus plasma, as the former may be more sensitive.

In addition, it is prudent to check for SARS-CoV-2 by PCR.

What are the major questions that remain and that you’d like to see elucidated going forward?

There are many. Is this a new disease? A new variant of adenovirus? A synergy or susceptibility related to SARS-CoV-2? Is it related to a variant of SARS-CoV-2? Is it triggering an adverse immune response? Are there other epigenetic factors involved? And finally, is this an increase, or is it related to a collective heightened concern following the pandemic?

Dr. Balistreri is the Dorothy M.M. Kersten Professor of Pediatrics, director emeritus of the Pediatric Liver Care Center, medical director emeritus of liver transplantation, and professor at the University of Cincinnati; he is also with the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

A version of this article first appeared on Medscape.com.

There has been increasing awareness of field cancerization in dermatology and how it relates to actinic damage, actinic keratoses (AKs), and the development of cutaneous squamous cell carcinomas (SCCs). The concept of field cancerization, which was first described in the context of oropharyngeal SCCs, attempted to explain the repeated observation of local recurrences that were instead multiple primary oropharyngeal SCCs occurring within a specific region of tissue. It was hypothesized that the tissue surrounding a malignancy also harbors irreversible oncogenic damage and therefore predisposes the surrounding tissue to developing further malignancy.¹ The development of additional malignant lesions would be considered distinct from a true recurrence of the original malignancy.

Field cancerization may be partially explained by a genetic basis, as mutations in the tumor suppressor gene, TP53—the most frequently observed mutation in cutaneous SCCs—also is found in sun-exposed but clinically normal skin.^2,3 The finding of oncogenic mutations in nonlesional skin supports the theory of field cancerization, in which a region contains multiple genetically altered populations, some of which may progress to cancer. Because there currently is no widely accepted clinical definition or validated clinical measurement of field cancerization in dermatology, it may be difficult for dermatologists to recognize which patients may be at risk for developing further malignancy in a potential area of field cancerization. Willenbrink et al⁴ updated the definition of field cancerization in dermatology as “multifocal clinical atypia characterized by AKs or SCCs in situ with or without invasive disease occurring in a field exposed to chronic UV radiation.” Managing patients with field cancerization can be challenging. Herein, we discuss updates to nonsurgical field-directed and lesion-directed therapies as well as other emerging therapies.

Field-Directed Therapies

Topical 5-fluorouracil (5-FU) and imiquimod cream 5% used as field-directed therapies help reduce the extent of AKs and actinic damage in areas of possible field cancerization.⁵ The addition of calcipotriol to topical 5-FU, which theoretically augments the skin’s T-cell antitumor response via the cytokine thymic stromal lymphopoietin, recently has been studied using short treatment courses resulting in an 87.8% reduction in AKs compared to a 26.3% reduction with topical 5-FU alone (when used twice daily for 4 days) and conferred a reduced risk of cutaneous SCCs 3 years after treatment (hazard ratio, 0.215 [95% CI, 0.048-0.972]; P=.032).^6,7 Chemowraps using topical 5-FU may be considered in more difficult-to-treat areas of field cancerization with multiple AKs or keratinocyte carcinomas of the lower extremities.⁸ The routine use of chemowraps—weekly application of 5-FU covered with an occlusive dressing—may be limited by the inability to control the extent of epidermal damage and subsequent systemic absorption. Ingenol mebutate, which was approved for treatment of AKs in 2012, was removed from both the European and US markets in 2020 because the medication may paradoxically increase the long-term incidence of skin cancer.⁹

Meta-analysis has shown that photodynamic therapy (PDT) with aminolevulinic acid demonstrated complete AK clearance in 75.8% of patients (N=156)(95% CI, 55.4%-96.2%).¹⁰ A more recent method of PDT using natural sunlight as the activation source demonstrated AK clearance of 95.5%, and it appeared to be a less painful alternative to traditional PDT.¹¹ Tacalcitol, another form of vitamin D, also has been shown to enhance the efficacy of PDT for AKs.¹²

Field-directed treatment with erbium:YAG and CO₂ lasers, which physically remove the actinically damaged epidermis, have been shown to possibly be as efficacious as topical 5-FU and 30% trichloroacetic acid (TCA) but possibly inferior to PDT.¹³ There has been growing interest in laser-assisted therapy, in which an ablative fractional laser is used to generate microscopic channels to theoretically enhance the absorption of a topical medication. A meta-analysis of the use of laser-assisted therapy for photosensitizing agents in PDT demonstrated a 33% increased chance of AK clearance compared to PDT alone (P<.01).¹⁴

Lesion-Directed Therapies

Multiple KAs or cutaneous SCCs may develop in an area of field cancerization, and surgically treating these multiple lesions in a concentrated area may be challenging. Intralesional agents, including methotrexate, 5-FU, bleomycin, and interferon, are known treatments for KAs.¹⁵ Intralesional 5-FU (25 mg once weekly for 3–4 weeks) in particular produced complete resolution in 92% of cutaneous SCCs and may be optimal for multiple or rapidly growing lesions, especially on the extremities.¹⁶

Oral Therapies

Oral therapies are considered in high-risk patients with multiple or recurrent cutaneous SCCs or in those who are immunosuppressed. Two trials demonstrated that nicotinamide 500 mg twice daily for 4 and 12 months decreased AKs by 29% to 35% and 13% (average of 3–5 fewer AKs as compared to baseline), respectively.^17,18 A meta-analysis found a reduction of cutaneous SCCs (rate ratio, 0.48 [95% CI, 0.26-0.88]; I²=67%; 552 patients, 5 trials), and given the favorable safety profile, nicotinamide can be considered for chemoprevention.¹⁹

Acitretin, shown to reduce AKs by 13.4% to 50%, is the primary oral chemoprevention recommended in transplant recipients.²⁰ Interestingly, a recent meta-analysis failed to find significant differences between the efficacy of acitretin and nicotinamide.²¹ The tolerability of acitretin requires serious consideration, as 52.2% of patients withdrew due to adverse effects in one trial.²²

Capecitabine (250–1150 mg twice daily), the oral form of 5-FU, decreased the incidence of AKs and cutaneous SCCs in 53% and 72% of transplant recipients, respectively.²³ Although several reports observed paradoxical eruptions of AKs following capecitabine for other malignancies, this actually underscores the efficacy of capecitabine, as the newly emerged AKs resolved thereafter.²⁴ Still, the evidence supporting capecitabine does not include any controlled studies.

Novel Therapies

In 2021, tirbanibulin ointment 1%, a Src tyrosine kinase inhibitor of tubulin polymerization that induces p53 expression and subsequent cell death, was approved by the US Food and Drug Administration for the treatment of AKs.²⁵ Two trials reported AK clearance rates of 44% and 54% with application of tirbanibulin once daily for 5 days (vs 5% and 13%, respectively, with placebo, each with P<.001) at 2 months and a sustained clearance rate of 27% at 1 year. The predominant adverse effects were local skin reactions, including application-site pain, pruritus, mild erythema, or scaling. Unlike in other treatments such as 5-FU or cryotherapy, erosions, dyspigmentation, or scarring were not notably observed.

Intralesional talimogene laherparepvec (T-VEC), an oncolytic, genetically modified herpes simplex virus type 1 that incites antitumor immune responses, received US Food and Drug Administration approval in 2015 for the treatment of cutaneous and lymph node metastases of melanoma that are unable to be surgically resected. More recently, T-VEC has been investigated for oropharyngeal SCC. A phase 1 and phase 2 trial of 17 stage III/IV SCC patients receiving T-VEC and cisplatin demonstrated pathologic remission in 14 of 15 (93%) patients, with 82.4% survival at 29 months.²⁶ A multicenter phase 1b trial of 36 patients with recurrent or metastatic head and neck SCCs treated with T-VEC and pembrolizumab exhibited a tolerable safety profile, and 5 cases had a partial response.²⁷ However, phase 3 trials of T-VEC have yet to be pursued. Regarding its potential use for cutaneous SCCs, it has been reportedly used in a liver transplant recipient with metastatic cutaneous SCCs who received 2 doses of T-VEC (1 month apart) and attained remission of disease.²⁸ There currently is a phase 2 trial examining the effectiveness of T-VEC in patients with cutaneous SCCs (ClinicalTrials.gov identifier NCT03714828).

Final Thoughts

It is important for dermatologists to bear in mind the possible role of field cancerization in their comprehensive care of patients at risk for multiple skin cancers. Management of areas of field cancerization can be challenging, particularly in patients who develop multiple KAs or cutaneous SCCs in a concentrated area and may need to involve different levels of treatment options, including field-directed therapies and lesion-directed therapies, as well as systemic chemoprevention.

There has been increasing awareness of field cancerization in dermatology and how it relates to actinic damage, actinic keratoses (AKs), and the development of cutaneous squamous cell carcinomas (SCCs). The concept of field cancerization, which was first described in the context of oropharyngeal SCCs, attempted to explain the repeated observation of local recurrences that were instead multiple primary oropharyngeal SCCs occurring within a specific region of tissue. It was hypothesized that the tissue surrounding a malignancy also harbors irreversible oncogenic damage and therefore predisposes the surrounding tissue to developing further malignancy.¹ The development of additional malignant lesions would be considered distinct from a true recurrence of the original malignancy.

Field cancerization may be partially explained by a genetic basis, as mutations in the tumor suppressor gene, TP53—the most frequently observed mutation in cutaneous SCCs—also is found in sun-exposed but clinically normal skin.^2,3 The finding of oncogenic mutations in nonlesional skin supports the theory of field cancerization, in which a region contains multiple genetically altered populations, some of which may progress to cancer. Because there currently is no widely accepted clinical definition or validated clinical measurement of field cancerization in dermatology, it may be difficult for dermatologists to recognize which patients may be at risk for developing further malignancy in a potential area of field cancerization. Willenbrink et al⁴ updated the definition of field cancerization in dermatology as “multifocal clinical atypia characterized by AKs or SCCs in situ with or without invasive disease occurring in a field exposed to chronic UV radiation.” Managing patients with field cancerization can be challenging. Herein, we discuss updates to nonsurgical field-directed and lesion-directed therapies as well as other emerging therapies.

Field-Directed Therapies

Topical 5-fluorouracil (5-FU) and imiquimod cream 5% used as field-directed therapies help reduce the extent of AKs and actinic damage in areas of possible field cancerization.⁵ The addition of calcipotriol to topical 5-FU, which theoretically augments the skin’s T-cell antitumor response via the cytokine thymic stromal lymphopoietin, recently has been studied using short treatment courses resulting in an 87.8% reduction in AKs compared to a 26.3% reduction with topical 5-FU alone (when used twice daily for 4 days) and conferred a reduced risk of cutaneous SCCs 3 years after treatment (hazard ratio, 0.215 [95% CI, 0.048-0.972]; P=.032).^6,7 Chemowraps using topical 5-FU may be considered in more difficult-to-treat areas of field cancerization with multiple AKs or keratinocyte carcinomas of the lower extremities.⁸ The routine use of chemowraps—weekly application of 5-FU covered with an occlusive dressing—may be limited by the inability to control the extent of epidermal damage and subsequent systemic absorption. Ingenol mebutate, which was approved for treatment of AKs in 2012, was removed from both the European and US markets in 2020 because the medication may paradoxically increase the long-term incidence of skin cancer.⁹

Meta-analysis has shown that photodynamic therapy (PDT) with aminolevulinic acid demonstrated complete AK clearance in 75.8% of patients (N=156)(95% CI, 55.4%-96.2%).¹⁰ A more recent method of PDT using natural sunlight as the activation source demonstrated AK clearance of 95.5%, and it appeared to be a less painful alternative to traditional PDT.¹¹ Tacalcitol, another form of vitamin D, also has been shown to enhance the efficacy of PDT for AKs.¹²

Field-directed treatment with erbium:YAG and CO₂ lasers, which physically remove the actinically damaged epidermis, have been shown to possibly be as efficacious as topical 5-FU and 30% trichloroacetic acid (TCA) but possibly inferior to PDT.¹³ There has been growing interest in laser-assisted therapy, in which an ablative fractional laser is used to generate microscopic channels to theoretically enhance the absorption of a topical medication. A meta-analysis of the use of laser-assisted therapy for photosensitizing agents in PDT demonstrated a 33% increased chance of AK clearance compared to PDT alone (P<.01).¹⁴

Lesion-Directed Therapies

Multiple KAs or cutaneous SCCs may develop in an area of field cancerization, and surgically treating these multiple lesions in a concentrated area may be challenging. Intralesional agents, including methotrexate, 5-FU, bleomycin, and interferon, are known treatments for KAs.¹⁵ Intralesional 5-FU (25 mg once weekly for 3–4 weeks) in particular produced complete resolution in 92% of cutaneous SCCs and may be optimal for multiple or rapidly growing lesions, especially on the extremities.¹⁶

Oral Therapies

Oral therapies are considered in high-risk patients with multiple or recurrent cutaneous SCCs or in those who are immunosuppressed. Two trials demonstrated that nicotinamide 500 mg twice daily for 4 and 12 months decreased AKs by 29% to 35% and 13% (average of 3–5 fewer AKs as compared to baseline), respectively.^17,18 A meta-analysis found a reduction of cutaneous SCCs (rate ratio, 0.48 [95% CI, 0.26-0.88]; I²=67%; 552 patients, 5 trials), and given the favorable safety profile, nicotinamide can be considered for chemoprevention.¹⁹

Acitretin, shown to reduce AKs by 13.4% to 50%, is the primary oral chemoprevention recommended in transplant recipients.²⁰ Interestingly, a recent meta-analysis failed to find significant differences between the efficacy of acitretin and nicotinamide.²¹ The tolerability of acitretin requires serious consideration, as 52.2% of patients withdrew due to adverse effects in one trial.²²

Capecitabine (250–1150 mg twice daily), the oral form of 5-FU, decreased the incidence of AKs and cutaneous SCCs in 53% and 72% of transplant recipients, respectively.²³ Although several reports observed paradoxical eruptions of AKs following capecitabine for other malignancies, this actually underscores the efficacy of capecitabine, as the newly emerged AKs resolved thereafter.²⁴ Still, the evidence supporting capecitabine does not include any controlled studies.

Novel Therapies

In 2021, tirbanibulin ointment 1%, a Src tyrosine kinase inhibitor of tubulin polymerization that induces p53 expression and subsequent cell death, was approved by the US Food and Drug Administration for the treatment of AKs.²⁵ Two trials reported AK clearance rates of 44% and 54% with application of tirbanibulin once daily for 5 days (vs 5% and 13%, respectively, with placebo, each with P<.001) at 2 months and a sustained clearance rate of 27% at 1 year. The predominant adverse effects were local skin reactions, including application-site pain, pruritus, mild erythema, or scaling. Unlike in other treatments such as 5-FU or cryotherapy, erosions, dyspigmentation, or scarring were not notably observed.

Intralesional talimogene laherparepvec (T-VEC), an oncolytic, genetically modified herpes simplex virus type 1 that incites antitumor immune responses, received US Food and Drug Administration approval in 2015 for the treatment of cutaneous and lymph node metastases of melanoma that are unable to be surgically resected. More recently, T-VEC has been investigated for oropharyngeal SCC. A phase 1 and phase 2 trial of 17 stage III/IV SCC patients receiving T-VEC and cisplatin demonstrated pathologic remission in 14 of 15 (93%) patients, with 82.4% survival at 29 months.²⁶ A multicenter phase 1b trial of 36 patients with recurrent or metastatic head and neck SCCs treated with T-VEC and pembrolizumab exhibited a tolerable safety profile, and 5 cases had a partial response.²⁷ However, phase 3 trials of T-VEC have yet to be pursued. Regarding its potential use for cutaneous SCCs, it has been reportedly used in a liver transplant recipient with metastatic cutaneous SCCs who received 2 doses of T-VEC (1 month apart) and attained remission of disease.²⁸ There currently is a phase 2 trial examining the effectiveness of T-VEC in patients with cutaneous SCCs (ClinicalTrials.gov identifier NCT03714828).

Final Thoughts

It is important for dermatologists to bear in mind the possible role of field cancerization in their comprehensive care of patients at risk for multiple skin cancers. Management of areas of field cancerization can be challenging, particularly in patients who develop multiple KAs or cutaneous SCCs in a concentrated area and may need to involve different levels of treatment options, including field-directed therapies and lesion-directed therapies, as well as systemic chemoprevention.

There has been increasing awareness of field cancerization in dermatology and how it relates to actinic damage, actinic keratoses (AKs), and the development of cutaneous squamous cell carcinomas (SCCs). The concept of field cancerization, which was first described in the context of oropharyngeal SCCs, attempted to explain the repeated observation of local recurrences that were instead multiple primary oropharyngeal SCCs occurring within a specific region of tissue. It was hypothesized that the tissue surrounding a malignancy also harbors irreversible oncogenic damage and therefore predisposes the surrounding tissue to developing further malignancy.¹ The development of additional malignant lesions would be considered distinct from a true recurrence of the original malignancy.

Field cancerization may be partially explained by a genetic basis, as mutations in the tumor suppressor gene, TP53—the most frequently observed mutation in cutaneous SCCs—also is found in sun-exposed but clinically normal skin.^2,3 The finding of oncogenic mutations in nonlesional skin supports the theory of field cancerization, in which a region contains multiple genetically altered populations, some of which may progress to cancer. Because there currently is no widely accepted clinical definition or validated clinical measurement of field cancerization in dermatology, it may be difficult for dermatologists to recognize which patients may be at risk for developing further malignancy in a potential area of field cancerization. Willenbrink et al⁴ updated the definition of field cancerization in dermatology as “multifocal clinical atypia characterized by AKs or SCCs in situ with or without invasive disease occurring in a field exposed to chronic UV radiation.” Managing patients with field cancerization can be challenging. Herein, we discuss updates to nonsurgical field-directed and lesion-directed therapies as well as other emerging therapies.

Field-Directed Therapies

Topical 5-fluorouracil (5-FU) and imiquimod cream 5% used as field-directed therapies help reduce the extent of AKs and actinic damage in areas of possible field cancerization.⁵ The addition of calcipotriol to topical 5-FU, which theoretically augments the skin’s T-cell antitumor response via the cytokine thymic stromal lymphopoietin, recently has been studied using short treatment courses resulting in an 87.8% reduction in AKs compared to a 26.3% reduction with topical 5-FU alone (when used twice daily for 4 days) and conferred a reduced risk of cutaneous SCCs 3 years after treatment (hazard ratio, 0.215 [95% CI, 0.048-0.972]; P=.032).^6,7 Chemowraps using topical 5-FU may be considered in more difficult-to-treat areas of field cancerization with multiple AKs or keratinocyte carcinomas of the lower extremities.⁸ The routine use of chemowraps—weekly application of 5-FU covered with an occlusive dressing—may be limited by the inability to control the extent of epidermal damage and subsequent systemic absorption. Ingenol mebutate, which was approved for treatment of AKs in 2012, was removed from both the European and US markets in 2020 because the medication may paradoxically increase the long-term incidence of skin cancer.⁹

Meta-analysis has shown that photodynamic therapy (PDT) with aminolevulinic acid demonstrated complete AK clearance in 75.8% of patients (N=156)(95% CI, 55.4%-96.2%).¹⁰ A more recent method of PDT using natural sunlight as the activation source demonstrated AK clearance of 95.5%, and it appeared to be a less painful alternative to traditional PDT.¹¹ Tacalcitol, another form of vitamin D, also has been shown to enhance the efficacy of PDT for AKs.¹²

Field-directed treatment with erbium:YAG and CO₂ lasers, which physically remove the actinically damaged epidermis, have been shown to possibly be as efficacious as topical 5-FU and 30% trichloroacetic acid (TCA) but possibly inferior to PDT.¹³ There has been growing interest in laser-assisted therapy, in which an ablative fractional laser is used to generate microscopic channels to theoretically enhance the absorption of a topical medication. A meta-analysis of the use of laser-assisted therapy for photosensitizing agents in PDT demonstrated a 33% increased chance of AK clearance compared to PDT alone (P<.01).¹⁴

Lesion-Directed Therapies

Multiple KAs or cutaneous SCCs may develop in an area of field cancerization, and surgically treating these multiple lesions in a concentrated area may be challenging. Intralesional agents, including methotrexate, 5-FU, bleomycin, and interferon, are known treatments for KAs.¹⁵ Intralesional 5-FU (25 mg once weekly for 3–4 weeks) in particular produced complete resolution in 92% of cutaneous SCCs and may be optimal for multiple or rapidly growing lesions, especially on the extremities.¹⁶

Oral Therapies

Oral therapies are considered in high-risk patients with multiple or recurrent cutaneous SCCs or in those who are immunosuppressed. Two trials demonstrated that nicotinamide 500 mg twice daily for 4 and 12 months decreased AKs by 29% to 35% and 13% (average of 3–5 fewer AKs as compared to baseline), respectively.^17,18 A meta-analysis found a reduction of cutaneous SCCs (rate ratio, 0.48 [95% CI, 0.26-0.88]; I²=67%; 552 patients, 5 trials), and given the favorable safety profile, nicotinamide can be considered for chemoprevention.¹⁹

Acitretin, shown to reduce AKs by 13.4% to 50%, is the primary oral chemoprevention recommended in transplant recipients.²⁰ Interestingly, a recent meta-analysis failed to find significant differences between the efficacy of acitretin and nicotinamide.²¹ The tolerability of acitretin requires serious consideration, as 52.2% of patients withdrew due to adverse effects in one trial.²²

Capecitabine (250–1150 mg twice daily), the oral form of 5-FU, decreased the incidence of AKs and cutaneous SCCs in 53% and 72% of transplant recipients, respectively.²³ Although several reports observed paradoxical eruptions of AKs following capecitabine for other malignancies, this actually underscores the efficacy of capecitabine, as the newly emerged AKs resolved thereafter.²⁴ Still, the evidence supporting capecitabine does not include any controlled studies.

Novel Therapies

In 2021, tirbanibulin ointment 1%, a Src tyrosine kinase inhibitor of tubulin polymerization that induces p53 expression and subsequent cell death, was approved by the US Food and Drug Administration for the treatment of AKs.²⁵ Two trials reported AK clearance rates of 44% and 54% with application of tirbanibulin once daily for 5 days (vs 5% and 13%, respectively, with placebo, each with P<.001) at 2 months and a sustained clearance rate of 27% at 1 year. The predominant adverse effects were local skin reactions, including application-site pain, pruritus, mild erythema, or scaling. Unlike in other treatments such as 5-FU or cryotherapy, erosions, dyspigmentation, or scarring were not notably observed.

Intralesional talimogene laherparepvec (T-VEC), an oncolytic, genetically modified herpes simplex virus type 1 that incites antitumor immune responses, received US Food and Drug Administration approval in 2015 for the treatment of cutaneous and lymph node metastases of melanoma that are unable to be surgically resected. More recently, T-VEC has been investigated for oropharyngeal SCC. A phase 1 and phase 2 trial of 17 stage III/IV SCC patients receiving T-VEC and cisplatin demonstrated pathologic remission in 14 of 15 (93%) patients, with 82.4% survival at 29 months.²⁶ A multicenter phase 1b trial of 36 patients with recurrent or metastatic head and neck SCCs treated with T-VEC and pembrolizumab exhibited a tolerable safety profile, and 5 cases had a partial response.²⁷ However, phase 3 trials of T-VEC have yet to be pursued. Regarding its potential use for cutaneous SCCs, it has been reportedly used in a liver transplant recipient with metastatic cutaneous SCCs who received 2 doses of T-VEC (1 month apart) and attained remission of disease.²⁸ There currently is a phase 2 trial examining the effectiveness of T-VEC in patients with cutaneous SCCs (ClinicalTrials.gov identifier NCT03714828).

Final Thoughts

It is important for dermatologists to bear in mind the possible role of field cancerization in their comprehensive care of patients at risk for multiple skin cancers. Management of areas of field cancerization can be challenging, particularly in patients who develop multiple KAs or cutaneous SCCs in a concentrated area and may need to involve different levels of treatment options, including field-directed therapies and lesion-directed therapies, as well as systemic chemoprevention.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

This is a transcript of a video that first appeared on Medscape.com. It has been edited for clarity.

On April 21, 2022, the Centers for Disease Control and Prevention released a Health Alert Network advisory regarding a cluster of nine cases of acute hepatitis in children in Alabama over a 5-month period from October 2021 to February 2022 – a rate substantially higher than what would be expected, given the relative rarity of hepatitis in children.

Standard workup was negative for the common causative agents – hepatitis A, B, and C – and no toxic exposures were identified. But there was one common thread among all these kids: They all tested positive for adenovirus.

And that is really strange.

There are about 100 circulating adenoviruses in the world that we know of, and around 50 of them infect humans. If you are an adult, it’s a virtual certainty that you have been infected with an adenovirus in the past. Most strains cause symptoms we would describe as the common cold: runny nose, sore throat. Some strains cause conjunctivitis (pink eye). Some cause gastrointestinal illness – the stomach bugs that kids get.

It’s the banality of adenovirus that makes this hepatitis finding so surprising.

The United States is not alone in reporting this new hepatitis syndrome. As of April 21, 169 cases have been reported across the world, including 114 in the United Kingdom.

Of the 169 cases reported worldwide, 74 had evidence of adenovirus infection. On molecular testing, 18 of those were adenovirus 41.

What I wanted to do today was go through the various hypotheses for what could be going on with these hepatitis cases, one by one, and highlight the evidence supporting them. We won’t reach a conclusion, but hopefully by the end, the path forward will be more clear. OK, let’s get started.

Hypothesis 1: Nothing is happening.

It’s worth noting that “clusters” of disease occur all the time, even when no relevant epidemiologic process has occurred. If there is some baseline rate of hepatitis, every once in a while, through bad luck alone, you’d see a group of cases all at once. This is known as the clustering illusion. And I’m quite confident in saying that this is not the case here.

For one, this phenomenon is worldwide, as we know from the World Health Organization report. In fact, the CDC didn’t provide the most detailed data about the nine (now 12) cases in the United States. This study from Scotland is the first to give a detailed accounting of cases, reporting on 13 cases of acute hepatitis of unknown cause in kids at a single hospital from January to April. Typically, the hospital sees fewer than four cases of hepatitis per year. Five of these 13 kids tested positive for adenovirus. So let’s take the clustering illusion off the list.

Hypothesis 2: It’s adenovirus.

The major evidence supporting adenovirus as the causative agent here is that a lot of these kids had adenovirus, and adenovirus 41 – a gut-tropic strain – in particular. This is important, because stool testing might be necessary for diagnosis and lots of kids with this condition didn’t get that. In other words, we have hard evidence of adenovirus infection in about 40% of the cases so far, but the true number might be substantially higher.

That said, adenovirus is seasonal, and we are in adenovirus season. Granted, 40% seems quite a bit higher than the background infection rate, but we have to be careful not to assume that correlation means causation.

The evidence against adenovirus, even adenovirus 41, is that this acute hepatitis syndrome is new, and adenovirus 41 is not. To be fair, we know adenoviruses can cause acute hepatitis, but the vast majority of reports are in immunocompromised individuals – organ transplant recipients and those with HIV. I was able to find just a handful of cases of immunocompetent kids developing hepatitis from adenovirus prior to this current outbreak.

The current outbreak would exceed the published literature by nearly two orders of magnitude. It feels like something else has to be going on.

Hypothesis 3: It’s coronavirus.

SARS-CoV-2 is a strange virus, both in its acute presentation and its long-term outcomes. It was clear early in the pandemic that some children infected by the coronavirus would develop MIS-C – multisystem inflammatory syndrome in children. MIS-C is associated with hepatitis in about 10% of children, according to this New England Journal of Medicine

But the presentation of these kids is quite different from MIS-C; fever is rare, for example. The WHO reports that of the 169 identified cases so far, 20 had active COVID infection. The Scotland cohort suggests that a similar proportion had past COVID infections. In other times, we might consider this a smoking gun, but at this point a history of COVID is not remarkable – after the Omicron wave, it’s about as common to have a history of COVID as it is not to have a history of COVID.

A brief aside here. This is not because of coronavirus vaccination. Of the more than 100 cases reported in the United Kingdom, none of these kids were vaccinated. So let’s put aside the possibility that this is a vaccine effect – there’s no real evidence to support that.

Which brings us to …

Hypothesis 4: It’s coronavirus and adenovirus.

This is sort of intriguing and can work a few different ways, via a direct and indirect path.

In the direct path, we posit that COVID infection does something to kids’ immune systems – something we don’t yet understand that limits their ability to fight off adenovirus. There is some support for this idea. This study in Immunity found that COVID infection can functionally impair dendritic cells and T-cells, including natural killer cells. These cells are important components of our innate antiviral immunity.

There’s an indirect path as well. COVID has led to lockdowns, distancing, masking – stuff that prevents kids from being exposed to germs from other kids. Could a lack of exposure to adenovirus or other viruses because of distancing increase the risk for severe disease when restrictions are lifted? Also possible – the severity of respiratory syncytial virus (RSV) infections this year is substantially higher than what we’ve seen in the past, for example.

And finally, hypothesis 5: This is something new.

We can’t ignore the possibility that this is simply a new disease-causing agent. Toxicology studies so far have been negative, and we wouldn’t expect hepatitis from a chemical toxin to appear in multiple countries around the world; this is almost certainly a biological phenomenon. It is possible that this is a new strain of adenovirus 41, or that adenovirus is a red herring altogether. Remember, we knew about “non-A/non-B viral hepatitis” for more than 2 decades before hepatitis C was discovered.

The pace of science is faster now, fortunately, and information is coming out quickly. As we learn more, we’ll share it with you.

Dr. Wilson, MD, MSCE, is an associate professor of medicine at Yale University, New Haven, Conn., and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. Dr. Wilson has disclosed no relevant financial relationships.

 

This is a transcript of a video that first appeared on Medscape.com. It has been edited for clarity.

On April 21, 2022, the Centers for Disease Control and Prevention released a Health Alert Network advisory regarding a cluster of nine cases of acute hepatitis in children in Alabama over a 5-month period from October 2021 to February 2022 – a rate substantially higher than what would be expected, given the relative rarity of hepatitis in children.

Standard workup was negative for the common causative agents – hepatitis A, B, and C – and no toxic exposures were identified. But there was one common thread among all these kids: They all tested positive for adenovirus.

And that is really strange.

There are about 100 circulating adenoviruses in the world that we know of, and around 50 of them infect humans. If you are an adult, it’s a virtual certainty that you have been infected with an adenovirus in the past. Most strains cause symptoms we would describe as the common cold: runny nose, sore throat. Some strains cause conjunctivitis (pink eye). Some cause gastrointestinal illness – the stomach bugs that kids get.

It’s the banality of adenovirus that makes this hepatitis finding so surprising.

The United States is not alone in reporting this new hepatitis syndrome. As of April 21, 169 cases have been reported across the world, including 114 in the United Kingdom.

Of the 169 cases reported worldwide, 74 had evidence of adenovirus infection. On molecular testing, 18 of those were adenovirus 41.

What I wanted to do today was go through the various hypotheses for what could be going on with these hepatitis cases, one by one, and highlight the evidence supporting them. We won’t reach a conclusion, but hopefully by the end, the path forward will be more clear. OK, let’s get started.

Hypothesis 1: Nothing is happening.

It’s worth noting that “clusters” of disease occur all the time, even when no relevant epidemiologic process has occurred. If there is some baseline rate of hepatitis, every once in a while, through bad luck alone, you’d see a group of cases all at once. This is known as the clustering illusion. And I’m quite confident in saying that this is not the case here.

For one, this phenomenon is worldwide, as we know from the World Health Organization report. In fact, the CDC didn’t provide the most detailed data about the nine (now 12) cases in the United States. This study from Scotland is the first to give a detailed accounting of cases, reporting on 13 cases of acute hepatitis of unknown cause in kids at a single hospital from January to April. Typically, the hospital sees fewer than four cases of hepatitis per year. Five of these 13 kids tested positive for adenovirus. So let’s take the clustering illusion off the list.

Hypothesis 2: It’s adenovirus.

The major evidence supporting adenovirus as the causative agent here is that a lot of these kids had adenovirus, and adenovirus 41 – a gut-tropic strain – in particular. This is important, because stool testing might be necessary for diagnosis and lots of kids with this condition didn’t get that. In other words, we have hard evidence of adenovirus infection in about 40% of the cases so far, but the true number might be substantially higher.

That said, adenovirus is seasonal, and we are in adenovirus season. Granted, 40% seems quite a bit higher than the background infection rate, but we have to be careful not to assume that correlation means causation.

The evidence against adenovirus, even adenovirus 41, is that this acute hepatitis syndrome is new, and adenovirus 41 is not. To be fair, we know adenoviruses can cause acute hepatitis, but the vast majority of reports are in immunocompromised individuals – organ transplant recipients and those with HIV. I was able to find just a handful of cases of immunocompetent kids developing hepatitis from adenovirus prior to this current outbreak.

The current outbreak would exceed the published literature by nearly two orders of magnitude. It feels like something else has to be going on.

Hypothesis 3: It’s coronavirus.

SARS-CoV-2 is a strange virus, both in its acute presentation and its long-term outcomes. It was clear early in the pandemic that some children infected by the coronavirus would develop MIS-C – multisystem inflammatory syndrome in children. MIS-C is associated with hepatitis in about 10% of children, according to this New England Journal of Medicine

But the presentation of these kids is quite different from MIS-C; fever is rare, for example. The WHO reports that of the 169 identified cases so far, 20 had active COVID infection. The Scotland cohort suggests that a similar proportion had past COVID infections. In other times, we might consider this a smoking gun, but at this point a history of COVID is not remarkable – after the Omicron wave, it’s about as common to have a history of COVID as it is not to have a history of COVID.

A brief aside here. This is not because of coronavirus vaccination. Of the more than 100 cases reported in the United Kingdom, none of these kids were vaccinated. So let’s put aside the possibility that this is a vaccine effect – there’s no real evidence to support that.

Which brings us to …

Hypothesis 4: It’s coronavirus and adenovirus.

This is sort of intriguing and can work a few different ways, via a direct and indirect path.

In the direct path, we posit that COVID infection does something to kids’ immune systems – something we don’t yet understand that limits their ability to fight off adenovirus. There is some support for this idea. This study in Immunity found that COVID infection can functionally impair dendritic cells and T-cells, including natural killer cells. These cells are important components of our innate antiviral immunity.

There’s an indirect path as well. COVID has led to lockdowns, distancing, masking – stuff that prevents kids from being exposed to germs from other kids. Could a lack of exposure to adenovirus or other viruses because of distancing increase the risk for severe disease when restrictions are lifted? Also possible – the severity of respiratory syncytial virus (RSV) infections this year is substantially higher than what we’ve seen in the past, for example.

And finally, hypothesis 5: This is something new.

We can’t ignore the possibility that this is simply a new disease-causing agent. Toxicology studies so far have been negative, and we wouldn’t expect hepatitis from a chemical toxin to appear in multiple countries around the world; this is almost certainly a biological phenomenon. It is possible that this is a new strain of adenovirus 41, or that adenovirus is a red herring altogether. Remember, we knew about “non-A/non-B viral hepatitis” for more than 2 decades before hepatitis C was discovered.

The pace of science is faster now, fortunately, and information is coming out quickly. As we learn more, we’ll share it with you.

Dr. Wilson, MD, MSCE, is an associate professor of medicine at Yale University, New Haven, Conn., and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. Dr. Wilson has disclosed no relevant financial relationships.

 

This is a transcript of a video that first appeared on Medscape.com. It has been edited for clarity.

On April 21, 2022, the Centers for Disease Control and Prevention released a Health Alert Network advisory regarding a cluster of nine cases of acute hepatitis in children in Alabama over a 5-month period from October 2021 to February 2022 – a rate substantially higher than what would be expected, given the relative rarity of hepatitis in children.

Standard workup was negative for the common causative agents – hepatitis A, B, and C – and no toxic exposures were identified. But there was one common thread among all these kids: They all tested positive for adenovirus.

And that is really strange.

There are about 100 circulating adenoviruses in the world that we know of, and around 50 of them infect humans. If you are an adult, it’s a virtual certainty that you have been infected with an adenovirus in the past. Most strains cause symptoms we would describe as the common cold: runny nose, sore throat. Some strains cause conjunctivitis (pink eye). Some cause gastrointestinal illness – the stomach bugs that kids get.

It’s the banality of adenovirus that makes this hepatitis finding so surprising.

The United States is not alone in reporting this new hepatitis syndrome. As of April 21, 169 cases have been reported across the world, including 114 in the United Kingdom.

Of the 169 cases reported worldwide, 74 had evidence of adenovirus infection. On molecular testing, 18 of those were adenovirus 41.

What I wanted to do today was go through the various hypotheses for what could be going on with these hepatitis cases, one by one, and highlight the evidence supporting them. We won’t reach a conclusion, but hopefully by the end, the path forward will be more clear. OK, let’s get started.

Hypothesis 1: Nothing is happening.

It’s worth noting that “clusters” of disease occur all the time, even when no relevant epidemiologic process has occurred. If there is some baseline rate of hepatitis, every once in a while, through bad luck alone, you’d see a group of cases all at once. This is known as the clustering illusion. And I’m quite confident in saying that this is not the case here.

For one, this phenomenon is worldwide, as we know from the World Health Organization report. In fact, the CDC didn’t provide the most detailed data about the nine (now 12) cases in the United States. This study from Scotland is the first to give a detailed accounting of cases, reporting on 13 cases of acute hepatitis of unknown cause in kids at a single hospital from January to April. Typically, the hospital sees fewer than four cases of hepatitis per year. Five of these 13 kids tested positive for adenovirus. So let’s take the clustering illusion off the list.

Hypothesis 2: It’s adenovirus.

The major evidence supporting adenovirus as the causative agent here is that a lot of these kids had adenovirus, and adenovirus 41 – a gut-tropic strain – in particular. This is important, because stool testing might be necessary for diagnosis and lots of kids with this condition didn’t get that. In other words, we have hard evidence of adenovirus infection in about 40% of the cases so far, but the true number might be substantially higher.

That said, adenovirus is seasonal, and we are in adenovirus season. Granted, 40% seems quite a bit higher than the background infection rate, but we have to be careful not to assume that correlation means causation.

The evidence against adenovirus, even adenovirus 41, is that this acute hepatitis syndrome is new, and adenovirus 41 is not. To be fair, we know adenoviruses can cause acute hepatitis, but the vast majority of reports are in immunocompromised individuals – organ transplant recipients and those with HIV. I was able to find just a handful of cases of immunocompetent kids developing hepatitis from adenovirus prior to this current outbreak.

The current outbreak would exceed the published literature by nearly two orders of magnitude. It feels like something else has to be going on.

Hypothesis 3: It’s coronavirus.

SARS-CoV-2 is a strange virus, both in its acute presentation and its long-term outcomes. It was clear early in the pandemic that some children infected by the coronavirus would develop MIS-C – multisystem inflammatory syndrome in children. MIS-C is associated with hepatitis in about 10% of children, according to this New England Journal of Medicine

But the presentation of these kids is quite different from MIS-C; fever is rare, for example. The WHO reports that of the 169 identified cases so far, 20 had active COVID infection. The Scotland cohort suggests that a similar proportion had past COVID infections. In other times, we might consider this a smoking gun, but at this point a history of COVID is not remarkable – after the Omicron wave, it’s about as common to have a history of COVID as it is not to have a history of COVID.

A brief aside here. This is not because of coronavirus vaccination. Of the more than 100 cases reported in the United Kingdom, none of these kids were vaccinated. So let’s put aside the possibility that this is a vaccine effect – there’s no real evidence to support that.

Which brings us to …

Hypothesis 4: It’s coronavirus and adenovirus.

This is sort of intriguing and can work a few different ways, via a direct and indirect path.

In the direct path, we posit that COVID infection does something to kids’ immune systems – something we don’t yet understand that limits their ability to fight off adenovirus. There is some support for this idea. This study in Immunity found that COVID infection can functionally impair dendritic cells and T-cells, including natural killer cells. These cells are important components of our innate antiviral immunity.

There’s an indirect path as well. COVID has led to lockdowns, distancing, masking – stuff that prevents kids from being exposed to germs from other kids. Could a lack of exposure to adenovirus or other viruses because of distancing increase the risk for severe disease when restrictions are lifted? Also possible – the severity of respiratory syncytial virus (RSV) infections this year is substantially higher than what we’ve seen in the past, for example.

And finally, hypothesis 5: This is something new.

We can’t ignore the possibility that this is simply a new disease-causing agent. Toxicology studies so far have been negative, and we wouldn’t expect hepatitis from a chemical toxin to appear in multiple countries around the world; this is almost certainly a biological phenomenon. It is possible that this is a new strain of adenovirus 41, or that adenovirus is a red herring altogether. Remember, we knew about “non-A/non-B viral hepatitis” for more than 2 decades before hepatitis C was discovered.

The pace of science is faster now, fortunately, and information is coming out quickly. As we learn more, we’ll share it with you.

Dr. Wilson, MD, MSCE, is an associate professor of medicine at Yale University, New Haven, Conn., and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at www.methodsman.com. Dr. Wilson has disclosed no relevant financial relationships.