Commentary

For the past 2 decades, catheter ablation stole most of the excitement in electrophysiology. Cardiac pacing was seen as necessary but boring. His-bundle pacing earned only modest attention. 

But at the annual scientific sessions of the Heart Rhythm Society, cardiac pacing consolidated its comeback and entered the super-cool category.

Not one but three late-breaking clinical trials considered the role of pacing the heart’s conduction system for both preventive and therapeutic purposes. Conduction system pacing, or CSP as we call it, includes pacing the His bundle or the left bundle branch. Left bundle–branch pacing has now largely replaced His-bundle pacing.

Before I tell you about the studies, let’s review why CSP disrupts the status quo.

The core idea goes back to basic physiology: After the impulse leaves the atrioventricular node, the heart’s specialized conduction system allows rapid and synchronous conduction to both the right and left ventricles.

Standard cardiac pacing means fixing a pacing lead into the muscle of the right ventricle. From that spot, conduction spreads via slower muscle-to-muscle conduction, which leads to a wide QRS complex and the right ventricle contracts before the left ventricle.

While such dyssynchronous contraction is better than no contraction, this approach leads to a pacing-induced cardiomyopathy in a substantial number of cases. (The incidence reported in many studies varies widely.)

The most disruptive effect of conduction system pacing is that it is a form of cardiac resynchronization therapy (CRT). And that is nifty because, until recently, resynchronizing the ventricles required placing two ventricular leads: one in the right ventricle and the other in the coronary sinus to pace the left ventricle.
 

Left bundle-branch pacing vs. biventricular pacing

The first of the three HRS studies is the LBBP-RESYNC randomized controlled trial led by Jiangang Zou, MD, PhD, and performed in multiple centers in China. It compared the efficacy of left bundle–branch pacing (LBBP) with that of conventional biventricular pacing in 40 patients with heart failure who were eligible for CRT. The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to 6-month follow-up.

The results favored LBBP. Although both pacing techniques improved LVEF from baseline, the between-group difference in LVEF was greater in the LBBP arm than the biventricular pacing arm by a statistically significant 5.6% (95% confidence interval, 0.3%-10.9%). Secondary endpoints, such as reductions in left ventricular end-systolic volume, N-terminal of the prohormone brain natriuretic peptide, and QRS duration, also favored LBBP.
 

Conduction system pacing vs. biventricular pacing

A second late-breaking study, from the Geisinger group, led by Pugazhendhi Vijayaraman, MD, was simultaneously published in Heart Rhythm.

This nonrandomized observational study compared nearly 500 patients eligible for CRT treated at two health systems. One group favors conduction system pacing and the other does traditional biventricular pacing, which set up a two-armed comparison.

CSP was accomplished by LBBP (65%) and His-bundle pacing (35%).

The primary endpoint of death or first hospitalization for heart failure occurred in 28.3% of patients in the CSP arm versus 38.4% of the biventricular arm (hazard ratio, 1.52; 95% CI, 1.08-2.09). QRS duration and LVEF also improved from baseline in both groups.
 

LBB area pacing as a bailout for failed CRT

The Geisinger group also presented and published an international multicenter study that assessed the feasibility of LBBP as a bailout when standard biventricular pacing did not work – because of inadequate coronary sinus anatomy or CRT nonresponse, defined as lack of clinical or echocardiographic improvement.

This series included 212 patients in whom CRT failed and who underwent attempted LBBP pacing. The bailout was successful in 200 patients (91%). The primary endpoint was defined as an increase in LVEF above 5% on echocardiography.

During 12-month follow-up, 61% of patients had an improvement in LVEF above 5% and nearly 30% had a “super-response,” defined as a 20% or greater increase or normalization of LVEF. Similar to the previous studies, LBBP resulted in shorter QRS duration and improved echocardiography parameters.
 

Am I persuaded?

I was an early adopter of His-bundle pacing. When successful, it delivered both aesthetically pleasing QRS complexes and clinical efficacy. But there were many challenges: it is technically difficult, and capture thresholds are often high at implant and get higher over time, which leads to shorter battery life.

Pacing the left bundle branch mitigates these challenges. Here, the operator approaches from the right side and screws the lead a few millimeters into the septum, so the tip of the lead can capture the left bundle or one of its branches. This allows activation of the heart’s specialized conduction system and thus synchronizes right and left ventricle contraction.

Although there is a learning curve, LBBP is technically easier than His-bundle pacing and ultimately results in far better pacing and sensing parameters. What’s more, the preferred lead for LBBP has a stellar efficacy record – over years.

Chormail/Dreamstime.com

The barriers to getting more CSP trials

The challenge going forward will be funding new trials. CSP stands to prevent pacing-induced cardiomyopathy and offer less costly alternatives to standard biventricular pacing for CRT. This is great for patients, but it would mean that fewer higher-cost CRT devices will be sold.

Heart rhythm research is largely industry-funded because in most cases better therapies for patients mean more profits for industry. In the case of CSP, there is no such confluence of interests.

Conduction system pacing has come about because of the efforts of a few tireless champions who not only published extensively but were also skilled at using social media to spread the excitement. Trials have been small and often self-funded.

The data presented at HRS provides enough equipoise to support a large outcomes-based randomized controlled trial. Imagine if our CSP champions were able to find public-funding sources for such future trials.

Now that would be super cool.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

For the past 2 decades, catheter ablation stole most of the excitement in electrophysiology. Cardiac pacing was seen as necessary but boring. His-bundle pacing earned only modest attention. 

But at the annual scientific sessions of the Heart Rhythm Society, cardiac pacing consolidated its comeback and entered the super-cool category.

Not one but three late-breaking clinical trials considered the role of pacing the heart’s conduction system for both preventive and therapeutic purposes. Conduction system pacing, or CSP as we call it, includes pacing the His bundle or the left bundle branch. Left bundle–branch pacing has now largely replaced His-bundle pacing.

Before I tell you about the studies, let’s review why CSP disrupts the status quo.

The core idea goes back to basic physiology: After the impulse leaves the atrioventricular node, the heart’s specialized conduction system allows rapid and synchronous conduction to both the right and left ventricles.

Standard cardiac pacing means fixing a pacing lead into the muscle of the right ventricle. From that spot, conduction spreads via slower muscle-to-muscle conduction, which leads to a wide QRS complex and the right ventricle contracts before the left ventricle.

While such dyssynchronous contraction is better than no contraction, this approach leads to a pacing-induced cardiomyopathy in a substantial number of cases. (The incidence reported in many studies varies widely.)

The most disruptive effect of conduction system pacing is that it is a form of cardiac resynchronization therapy (CRT). And that is nifty because, until recently, resynchronizing the ventricles required placing two ventricular leads: one in the right ventricle and the other in the coronary sinus to pace the left ventricle.
 

Left bundle-branch pacing vs. biventricular pacing

The first of the three HRS studies is the LBBP-RESYNC randomized controlled trial led by Jiangang Zou, MD, PhD, and performed in multiple centers in China. It compared the efficacy of left bundle–branch pacing (LBBP) with that of conventional biventricular pacing in 40 patients with heart failure who were eligible for CRT. The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to 6-month follow-up.

The results favored LBBP. Although both pacing techniques improved LVEF from baseline, the between-group difference in LVEF was greater in the LBBP arm than the biventricular pacing arm by a statistically significant 5.6% (95% confidence interval, 0.3%-10.9%). Secondary endpoints, such as reductions in left ventricular end-systolic volume, N-terminal of the prohormone brain natriuretic peptide, and QRS duration, also favored LBBP.
 

Conduction system pacing vs. biventricular pacing

A second late-breaking study, from the Geisinger group, led by Pugazhendhi Vijayaraman, MD, was simultaneously published in Heart Rhythm.

This nonrandomized observational study compared nearly 500 patients eligible for CRT treated at two health systems. One group favors conduction system pacing and the other does traditional biventricular pacing, which set up a two-armed comparison.

CSP was accomplished by LBBP (65%) and His-bundle pacing (35%).

The primary endpoint of death or first hospitalization for heart failure occurred in 28.3% of patients in the CSP arm versus 38.4% of the biventricular arm (hazard ratio, 1.52; 95% CI, 1.08-2.09). QRS duration and LVEF also improved from baseline in both groups.
 

LBB area pacing as a bailout for failed CRT

The Geisinger group also presented and published an international multicenter study that assessed the feasibility of LBBP as a bailout when standard biventricular pacing did not work – because of inadequate coronary sinus anatomy or CRT nonresponse, defined as lack of clinical or echocardiographic improvement.

This series included 212 patients in whom CRT failed and who underwent attempted LBBP pacing. The bailout was successful in 200 patients (91%). The primary endpoint was defined as an increase in LVEF above 5% on echocardiography.

During 12-month follow-up, 61% of patients had an improvement in LVEF above 5% and nearly 30% had a “super-response,” defined as a 20% or greater increase or normalization of LVEF. Similar to the previous studies, LBBP resulted in shorter QRS duration and improved echocardiography parameters.
 

Am I persuaded?

I was an early adopter of His-bundle pacing. When successful, it delivered both aesthetically pleasing QRS complexes and clinical efficacy. But there were many challenges: it is technically difficult, and capture thresholds are often high at implant and get higher over time, which leads to shorter battery life.

Pacing the left bundle branch mitigates these challenges. Here, the operator approaches from the right side and screws the lead a few millimeters into the septum, so the tip of the lead can capture the left bundle or one of its branches. This allows activation of the heart’s specialized conduction system and thus synchronizes right and left ventricle contraction.

Although there is a learning curve, LBBP is technically easier than His-bundle pacing and ultimately results in far better pacing and sensing parameters. What’s more, the preferred lead for LBBP has a stellar efficacy record – over years.

Chormail/Dreamstime.com

The barriers to getting more CSP trials

The challenge going forward will be funding new trials. CSP stands to prevent pacing-induced cardiomyopathy and offer less costly alternatives to standard biventricular pacing for CRT. This is great for patients, but it would mean that fewer higher-cost CRT devices will be sold.

Heart rhythm research is largely industry-funded because in most cases better therapies for patients mean more profits for industry. In the case of CSP, there is no such confluence of interests.

Conduction system pacing has come about because of the efforts of a few tireless champions who not only published extensively but were also skilled at using social media to spread the excitement. Trials have been small and often self-funded.

The data presented at HRS provides enough equipoise to support a large outcomes-based randomized controlled trial. Imagine if our CSP champions were able to find public-funding sources for such future trials.

Now that would be super cool.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

For the past 2 decades, catheter ablation stole most of the excitement in electrophysiology. Cardiac pacing was seen as necessary but boring. His-bundle pacing earned only modest attention. 

But at the annual scientific sessions of the Heart Rhythm Society, cardiac pacing consolidated its comeback and entered the super-cool category.

Not one but three late-breaking clinical trials considered the role of pacing the heart’s conduction system for both preventive and therapeutic purposes. Conduction system pacing, or CSP as we call it, includes pacing the His bundle or the left bundle branch. Left bundle–branch pacing has now largely replaced His-bundle pacing.

Before I tell you about the studies, let’s review why CSP disrupts the status quo.

The core idea goes back to basic physiology: After the impulse leaves the atrioventricular node, the heart’s specialized conduction system allows rapid and synchronous conduction to both the right and left ventricles.

Standard cardiac pacing means fixing a pacing lead into the muscle of the right ventricle. From that spot, conduction spreads via slower muscle-to-muscle conduction, which leads to a wide QRS complex and the right ventricle contracts before the left ventricle.

While such dyssynchronous contraction is better than no contraction, this approach leads to a pacing-induced cardiomyopathy in a substantial number of cases. (The incidence reported in many studies varies widely.)

The most disruptive effect of conduction system pacing is that it is a form of cardiac resynchronization therapy (CRT). And that is nifty because, until recently, resynchronizing the ventricles required placing two ventricular leads: one in the right ventricle and the other in the coronary sinus to pace the left ventricle.
 

Left bundle-branch pacing vs. biventricular pacing

The first of the three HRS studies is the LBBP-RESYNC randomized controlled trial led by Jiangang Zou, MD, PhD, and performed in multiple centers in China. It compared the efficacy of left bundle–branch pacing (LBBP) with that of conventional biventricular pacing in 40 patients with heart failure who were eligible for CRT. The primary endpoint was the change in left ventricular ejection fraction (LVEF) from baseline to 6-month follow-up.

The results favored LBBP. Although both pacing techniques improved LVEF from baseline, the between-group difference in LVEF was greater in the LBBP arm than the biventricular pacing arm by a statistically significant 5.6% (95% confidence interval, 0.3%-10.9%). Secondary endpoints, such as reductions in left ventricular end-systolic volume, N-terminal of the prohormone brain natriuretic peptide, and QRS duration, also favored LBBP.
 

Conduction system pacing vs. biventricular pacing

A second late-breaking study, from the Geisinger group, led by Pugazhendhi Vijayaraman, MD, was simultaneously published in Heart Rhythm.

This nonrandomized observational study compared nearly 500 patients eligible for CRT treated at two health systems. One group favors conduction system pacing and the other does traditional biventricular pacing, which set up a two-armed comparison.

CSP was accomplished by LBBP (65%) and His-bundle pacing (35%).

The primary endpoint of death or first hospitalization for heart failure occurred in 28.3% of patients in the CSP arm versus 38.4% of the biventricular arm (hazard ratio, 1.52; 95% CI, 1.08-2.09). QRS duration and LVEF also improved from baseline in both groups.
 

LBB area pacing as a bailout for failed CRT

The Geisinger group also presented and published an international multicenter study that assessed the feasibility of LBBP as a bailout when standard biventricular pacing did not work – because of inadequate coronary sinus anatomy or CRT nonresponse, defined as lack of clinical or echocardiographic improvement.

This series included 212 patients in whom CRT failed and who underwent attempted LBBP pacing. The bailout was successful in 200 patients (91%). The primary endpoint was defined as an increase in LVEF above 5% on echocardiography.

During 12-month follow-up, 61% of patients had an improvement in LVEF above 5% and nearly 30% had a “super-response,” defined as a 20% or greater increase or normalization of LVEF. Similar to the previous studies, LBBP resulted in shorter QRS duration and improved echocardiography parameters.
 

Am I persuaded?

I was an early adopter of His-bundle pacing. When successful, it delivered both aesthetically pleasing QRS complexes and clinical efficacy. But there were many challenges: it is technically difficult, and capture thresholds are often high at implant and get higher over time, which leads to shorter battery life.

Pacing the left bundle branch mitigates these challenges. Here, the operator approaches from the right side and screws the lead a few millimeters into the septum, so the tip of the lead can capture the left bundle or one of its branches. This allows activation of the heart’s specialized conduction system and thus synchronizes right and left ventricle contraction.

Although there is a learning curve, LBBP is technically easier than His-bundle pacing and ultimately results in far better pacing and sensing parameters. What’s more, the preferred lead for LBBP has a stellar efficacy record – over years.

Chormail/Dreamstime.com

The barriers to getting more CSP trials

The challenge going forward will be funding new trials. CSP stands to prevent pacing-induced cardiomyopathy and offer less costly alternatives to standard biventricular pacing for CRT. This is great for patients, but it would mean that fewer higher-cost CRT devices will be sold.

Heart rhythm research is largely industry-funded because in most cases better therapies for patients mean more profits for industry. In the case of CSP, there is no such confluence of interests.

Conduction system pacing has come about because of the efforts of a few tireless champions who not only published extensively but were also skilled at using social media to spread the excitement. Trials have been small and often self-funded.

The data presented at HRS provides enough equipoise to support a large outcomes-based randomized controlled trial. Imagine if our CSP champions were able to find public-funding sources for such future trials.

Now that would be super cool.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Recently the National Clinical Care Commission provided recommendations to Congress for improving federal diabetes programs in a report. This commission was put together after Congress passed the National Clinical Care Commission Act in 2017.

The report provides a wide range of recommendations that look to combat and prevent diabetes at many levels. An exciting aspect of the recommendations is that they consider how all agencies, including those that are not specifically health care, can fight diabetes. As primary care physicians are increasingly looking at all aspects of our patients’ lives to improve their health, these recommendations provide support for the work on which we are currently embarking.

The report acknowledges that many recent advances in diabetes treatments have made huge differences for clinicians and patients alike. Unfortunately, they have not been translated quickly into practice and when they have been, there have been disparities in the rollouts.

The document also states that many other factors, including housing, health care access, and food access, greatly affect the prevention and control of diabetes, according to a paper published in Annals of Internal Medicine. These factors have led to significant disparities in the population impacted by diabetes.

The topic areas of the recommendations include federal programs and policies; population-level programs to prevent diabetes, facilitate treatments, and promote health equity; type 2 diabetes prevention; insurance coverage; diabetes care delivery; and diabetes research.

Supporting recommendations in clinics

Family physicians, internists, and pediatricians can directly support many of the recommendations in their clinics. For those recommendations that are not directed at primary care clinics specifically, physicians should provide advocacy for their implementation.

If implemented, some of these recommendations will allow primary care physicians to improve at providing treatments to their patients for diabetes prevention and treatment of the disease. For example, the recommendations call for requirements of insurance companies to cover screening for prediabetes with the use of hemoglobin A1c and the participation in Centers for Disease Control and Prevention–recognized diabetes prevention programs.

The recommendations also call for the requirement of high-value diabetes services and treatment to be covered predeductible by insurers. If more consistently covered by insurers, it would be easier for us to implement these opportunities including educational groups in our practices. Additionally, if they were available predeductible, we could recommend these to our patients with less worry about cost.

Within care delivery recommendations, they also highlight the importance of an adequate and sustainable team to enhance care for patients with diabetes. Many of us know that it takes more than just the medications, but also significant counseling on diet, exercise and other lifestyle aspects – which need to be tailored to each patient for both prevention and treatment of diabetes.

The recommendations also call for the education and treatment modalities to be able to be provided and covered via virtual methods, while potentially increasing physicians’ ability to provide and patients’ ability to access. Ensuring both the workforce is available and that insurance provides coverage would make these programs accessible to so many more physician offices and ultimately patients.
 

Importance of social factors

As stated earlier, one of the great aspects of this report is its acknowledgment of the importance of social factors on the prevention and treatment of diabetes.

The report recommends expanding housing opportunities for low-income individuals as individuals cannot focus on their health when worried about housing. It also recommends increasing assistance with programs focused on food security. Primary care physicians should advocate for the adoption of these and other recommendations, because of the potentially meaningful impact these changes could have.

Ensuring adequate housing and access to healthy food would go a long way in the prevention and treatment of diabetes. If there are increases in these resources, team members within primary care physician offices would be wonderful allies to help direct patients to these resources. As these concerns may be top of mind for some patients, linking patients to these resources in the physician’s office may reinforce for patients that physicians understand our patients’ biggest concerns.

Ultimately, if the sweeping recommendations in this report are adopted and enforced, it could mean significant improvements for many patients at risk for and living with diabetes. They would provide payment for these resources making them more accessible for patients and physicians alike.

Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

Recently the National Clinical Care Commission provided recommendations to Congress for improving federal diabetes programs in a report. This commission was put together after Congress passed the National Clinical Care Commission Act in 2017.

The report provides a wide range of recommendations that look to combat and prevent diabetes at many levels. An exciting aspect of the recommendations is that they consider how all agencies, including those that are not specifically health care, can fight diabetes. As primary care physicians are increasingly looking at all aspects of our patients’ lives to improve their health, these recommendations provide support for the work on which we are currently embarking.

The report acknowledges that many recent advances in diabetes treatments have made huge differences for clinicians and patients alike. Unfortunately, they have not been translated quickly into practice and when they have been, there have been disparities in the rollouts.

The document also states that many other factors, including housing, health care access, and food access, greatly affect the prevention and control of diabetes, according to a paper published in Annals of Internal Medicine. These factors have led to significant disparities in the population impacted by diabetes.

The topic areas of the recommendations include federal programs and policies; population-level programs to prevent diabetes, facilitate treatments, and promote health equity; type 2 diabetes prevention; insurance coverage; diabetes care delivery; and diabetes research.

Supporting recommendations in clinics

Family physicians, internists, and pediatricians can directly support many of the recommendations in their clinics. For those recommendations that are not directed at primary care clinics specifically, physicians should provide advocacy for their implementation.

If implemented, some of these recommendations will allow primary care physicians to improve at providing treatments to their patients for diabetes prevention and treatment of the disease. For example, the recommendations call for requirements of insurance companies to cover screening for prediabetes with the use of hemoglobin A1c and the participation in Centers for Disease Control and Prevention–recognized diabetes prevention programs.

The recommendations also call for the requirement of high-value diabetes services and treatment to be covered predeductible by insurers. If more consistently covered by insurers, it would be easier for us to implement these opportunities including educational groups in our practices. Additionally, if they were available predeductible, we could recommend these to our patients with less worry about cost.

Within care delivery recommendations, they also highlight the importance of an adequate and sustainable team to enhance care for patients with diabetes. Many of us know that it takes more than just the medications, but also significant counseling on diet, exercise and other lifestyle aspects – which need to be tailored to each patient for both prevention and treatment of diabetes.

The recommendations also call for the education and treatment modalities to be able to be provided and covered via virtual methods, while potentially increasing physicians’ ability to provide and patients’ ability to access. Ensuring both the workforce is available and that insurance provides coverage would make these programs accessible to so many more physician offices and ultimately patients.
 

Importance of social factors

As stated earlier, one of the great aspects of this report is its acknowledgment of the importance of social factors on the prevention and treatment of diabetes.

The report recommends expanding housing opportunities for low-income individuals as individuals cannot focus on their health when worried about housing. It also recommends increasing assistance with programs focused on food security. Primary care physicians should advocate for the adoption of these and other recommendations, because of the potentially meaningful impact these changes could have.

Ensuring adequate housing and access to healthy food would go a long way in the prevention and treatment of diabetes. If there are increases in these resources, team members within primary care physician offices would be wonderful allies to help direct patients to these resources. As these concerns may be top of mind for some patients, linking patients to these resources in the physician’s office may reinforce for patients that physicians understand our patients’ biggest concerns.

Ultimately, if the sweeping recommendations in this report are adopted and enforced, it could mean significant improvements for many patients at risk for and living with diabetes. They would provide payment for these resources making them more accessible for patients and physicians alike.

Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

Recently the National Clinical Care Commission provided recommendations to Congress for improving federal diabetes programs in a report. This commission was put together after Congress passed the National Clinical Care Commission Act in 2017.

The report provides a wide range of recommendations that look to combat and prevent diabetes at many levels. An exciting aspect of the recommendations is that they consider how all agencies, including those that are not specifically health care, can fight diabetes. As primary care physicians are increasingly looking at all aspects of our patients’ lives to improve their health, these recommendations provide support for the work on which we are currently embarking.

The report acknowledges that many recent advances in diabetes treatments have made huge differences for clinicians and patients alike. Unfortunately, they have not been translated quickly into practice and when they have been, there have been disparities in the rollouts.

The document also states that many other factors, including housing, health care access, and food access, greatly affect the prevention and control of diabetes, according to a paper published in Annals of Internal Medicine. These factors have led to significant disparities in the population impacted by diabetes.

The topic areas of the recommendations include federal programs and policies; population-level programs to prevent diabetes, facilitate treatments, and promote health equity; type 2 diabetes prevention; insurance coverage; diabetes care delivery; and diabetes research.

Supporting recommendations in clinics

Family physicians, internists, and pediatricians can directly support many of the recommendations in their clinics. For those recommendations that are not directed at primary care clinics specifically, physicians should provide advocacy for their implementation.

If implemented, some of these recommendations will allow primary care physicians to improve at providing treatments to their patients for diabetes prevention and treatment of the disease. For example, the recommendations call for requirements of insurance companies to cover screening for prediabetes with the use of hemoglobin A1c and the participation in Centers for Disease Control and Prevention–recognized diabetes prevention programs.

The recommendations also call for the requirement of high-value diabetes services and treatment to be covered predeductible by insurers. If more consistently covered by insurers, it would be easier for us to implement these opportunities including educational groups in our practices. Additionally, if they were available predeductible, we could recommend these to our patients with less worry about cost.

Within care delivery recommendations, they also highlight the importance of an adequate and sustainable team to enhance care for patients with diabetes. Many of us know that it takes more than just the medications, but also significant counseling on diet, exercise and other lifestyle aspects – which need to be tailored to each patient for both prevention and treatment of diabetes.

The recommendations also call for the education and treatment modalities to be able to be provided and covered via virtual methods, while potentially increasing physicians’ ability to provide and patients’ ability to access. Ensuring both the workforce is available and that insurance provides coverage would make these programs accessible to so many more physician offices and ultimately patients.
 

Importance of social factors

As stated earlier, one of the great aspects of this report is its acknowledgment of the importance of social factors on the prevention and treatment of diabetes.

The report recommends expanding housing opportunities for low-income individuals as individuals cannot focus on their health when worried about housing. It also recommends increasing assistance with programs focused on food security. Primary care physicians should advocate for the adoption of these and other recommendations, because of the potentially meaningful impact these changes could have.

Ensuring adequate housing and access to healthy food would go a long way in the prevention and treatment of diabetes. If there are increases in these resources, team members within primary care physician offices would be wonderful allies to help direct patients to these resources. As these concerns may be top of mind for some patients, linking patients to these resources in the physician’s office may reinforce for patients that physicians understand our patients’ biggest concerns.

Ultimately, if the sweeping recommendations in this report are adopted and enforced, it could mean significant improvements for many patients at risk for and living with diabetes. They would provide payment for these resources making them more accessible for patients and physicians alike.

Dr. Wheat is a family physician at Erie Family Health Center and program director of Northwestern University’s McGaw Family Medicine residency program, both in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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 [email protected].

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.