Commentary

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tracing the outbreak in the United States

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

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

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

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

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

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

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

European and global cases

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

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

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

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

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

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

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

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

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

Not to my knowledge.
 

What clinicians need to know

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tracing the outbreak in the United States

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

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

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

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

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

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

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

European and global cases

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

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

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

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

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

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

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

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

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

Not to my knowledge.
 

What clinicians need to know

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Tracing the outbreak in the United States

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

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

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

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

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

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

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

European and global cases

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

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

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

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

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

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

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

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

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

Not to my knowledge.
 

What clinicians need to know

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Field-Directed Therapies

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

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

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

Lesion-Directed Therapies

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

Oral Therapies

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

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

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

Novel Therapies

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

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

Final Thoughts

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

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

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

Field-Directed Therapies

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

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

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

Lesion-Directed Therapies

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

Oral Therapies

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

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

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

Novel Therapies

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

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

Final Thoughts

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

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

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

Field-Directed Therapies

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

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

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

Lesion-Directed Therapies

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

Oral Therapies

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

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

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

Novel Therapies

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

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

Final Thoughts

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

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

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

Transitioning from active therapy to symptom management

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Transitioning from active therapy to symptom management

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Transitioning from active therapy to symptom management

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

And that is really strange.

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

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

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

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

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

Hypothesis 1: Nothing is happening.

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

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

Hypothesis 2: It’s adenovirus.

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

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

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

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

Hypothesis 3: It’s coronavirus.

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

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

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

Which brings us to …

Hypothesis 4: It’s coronavirus and adenovirus.

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

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

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

And finally, hypothesis 5: This is something new.

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

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

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

 

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

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

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

And that is really strange.

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

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

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

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

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

Hypothesis 1: Nothing is happening.

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

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

Hypothesis 2: It’s adenovirus.

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

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

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

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

Hypothesis 3: It’s coronavirus.

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

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

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

Which brings us to …

Hypothesis 4: It’s coronavirus and adenovirus.

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

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

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

And finally, hypothesis 5: This is something new.

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

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

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

 

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

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

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

And that is really strange.

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

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

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

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

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

Hypothesis 1: Nothing is happening.

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

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

Hypothesis 2: It’s adenovirus.

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

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

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

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

Hypothesis 3: It’s coronavirus.

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

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

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

Which brings us to …

Hypothesis 4: It’s coronavirus and adenovirus.

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

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

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

And finally, hypothesis 5: This is something new.

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

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

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

 

Mood instability, or sudden, unpredictable, and frequent shifts in emotional states, characterizes many types of psychiatric disorder, including attention-deficit/hyperactivity disorder (ADHD), personality disorders, depression, and posttraumatic stress disorder. To say that individuals with bipolar disorder (BD) have mood instability sounds like a tautology. Nonetheless, mood instability has particular relevance to BD: Many patients have irregular or labile moods even when they are between major episodes of mania and depression.¹

Children of parents with BD who have high levels of mood instability are at particularly high risk for developing BD (types I or II) in late adolescence or early adulthood.² The following case provides an illustration:

Patrick, age 14, entered treatment with diagnoses of ADHD and other specified bipolar disorder. His mother felt that his behavior resembled that of his father, who had been treated for manic episodes. During the COVID-19 pandemic, Patrick had become increasingly difficult at home, with significant oppositionality, impulsive behavior, and difficulty following through on school assignments or household tasks. His mother’s most significant complaints concerned Patrick’s sudden outbursts of anger and abrupt verbal abuse when she asked him to stop playing video games. When interrupted, he cursed loudly and sometimes turned violent; he had broken a window and a door at home and had on one occasion physically attacked his younger brother. Patrick agreed that he became angry at times, but felt that others provoked him. When queried about depression, he described anxiety and worry. He was unable to describe a particular trigger for his anxiety except for being interrupted in online games with his friends, which made him “feel like a total loser.”

His mother reported that Patrick had multiple 1- to 2-day intervals in which he became “really silly, laughing at nothing,” talking rapidly, jumping from one topic to another, and becoming annoyed when others didn’t share his enthusiasm. In these activated intervals, he slept little and seemed to be full of energy; his mother would hear him talking loudly into his phone throughout the night. During one such interval he had become verbally aggressive with a peer, which had ruined their friendship. Both Patrick and his mother reported that they had been fighting constantly and, in her words, “our house has become a war zone.”

In our recent article in the Journal of the American Academy of Child and Adolescent Psychiatry,³ my coauthors and I examined the association between parents’ ratings of mood instability and clinicians’ longitudinal ratings of symptoms and functioning among youth (ages 9-17 years) who were at high risk for BD. The participants met DSM-5 diagnostic criteria for major depressive disorder or other specified BD, defined as recurrent and brief periods of elevation and activation that did not meet syndromal mania or hypomania criteria. All participants had at least one first- or second-degree family member with a history of BD I or II. Following a period of evaluation, participants were randomly assigned to one of two 4-month psychological therapies: Family-focused therapy (12 sessions of psychoeducation, communication training, and problem-solving skills training) or enhanced usual care (6 sessions of family and individual psychoeducation and support). They also received pharmacological management from study-affiliated psychiatrists when warranted.

We measured mood instability at intake and every 4-6 months over an average of 2 years (range 0-255 weeks). We used a brief parent questionnaire – the Children’s Affective Lability Scale⁴ – which enables measurement of lability on the dimensions of elevation or activation (e.g., bursts of silliness or hilarity, excessive familiarity with others), irritability (e.g., temper outbursts), or anxious-depression (e.g., sudden bouts of crying).

Over the 1- to 4-year period of follow-up, mood instability was associated with poor prognosis indicators in high-risk youth: Being younger, having younger ages at first symptom onset, being diagnosed with other specified BD (vs. major depression), and having more complex patterns of comorbid disorders. Mood instability tracked closely with levels of mania, depression, and global functioning over the follow-up. There was a temporal pathway between a diagnosis of other specified bipolar disorder at intake and higher levels of mood instability at follow-up, which in turn predicted higher levels of parent/child conflict. High levels of mood lability may lead to isolation from peers and tension within family relationships, which may fuel further children’s expressions of frustration, rage, depression, or impulsive behavior.

Youth with higher levels of mood instability required more complex medication regimens over 1 year than did those with lower instability. There was an overall reduction in mood instability as children aged (or spent more time in treatment). Over the 1- to 4-year follow-up, family-focused therapy was associated with longer intervals prior to new mood episodes than was enhanced usual care, but reductions in mood instability were independent of the type of psychosocial treatment assigned to children.

The participants in this study could not be followed long enough to determine whether levels of mood instability were associated with the later development of syndromal BD. Other studies, however, have documented this relationship. Large-scale longitudinal studies of high-risk children find that measures of mood lability – along with early onset manic symptoms, depression, anxiety, and a family history of mania or hypomania – can be combined to calculate the risk that any individual child will develop BD I or II over the next 5-8 years.^2,5

Clinicians should include measurement of the severity and psychosocial determinants of persistent mood shifts in youth under their care, particularly those with a family history of BD. Mood instability is associated with more severe symptom trajectories, more social isolation, and greater distress and conflict within the family. It may require a greater intensity of both pharmacological and psychosocial treatments to treat existing symptoms and functional impairments, and to prevent further mood deterioration.

Dr. Miklowitz is Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior. He is the author of “The Bipolar Disorder Survival Guide, 3rd Ed.” (New York: Guilford Press, 2019) and “Bipolar Disorder: A Family-Focused Treatment Approach, 2nd Ed” (New York: Guilford Press, 2010). He has no conflicts of interest to disclose. Contact Dr. Miklowitz at dmiklowitz@mednet.ucla.edu.

References

1. Bonsall MB, et al. Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder. Proc Biol Sci. Mar 7 2012;279(1730):916-24. doi: 10.1098/rspb.2011.1246.

2. Hafeman DM, et al. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173(7):695-704. doi: 10.1176/appi.ajp.2015.15040414.

3. Miklowitz DJ, et al. Mood instability in youth at high risk for bipolar disorder. J Am Acad Child Adol Psychiatry. 2022 Mar 17;S0890-8567(22)00118-6. doi: 10.1016/j.jaac.2022.03.009.

4. Gerson AC, et al. The Children’s Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. Dec 20 1996;65(3):189-98. doi: 10.1016/s0165-1781(96)02851-x.

5. Birmaher B, et al. A risk calculator to predict the individual risk of conversion from subthreshold bipolar symptoms to bipolar disorder I or II in youth. J Am Acad Child Adol Psychiatry. 2018;57(10):755-63. doi: 10.1016/j.jaac.2018.05.023.

Mood instability, or sudden, unpredictable, and frequent shifts in emotional states, characterizes many types of psychiatric disorder, including attention-deficit/hyperactivity disorder (ADHD), personality disorders, depression, and posttraumatic stress disorder. To say that individuals with bipolar disorder (BD) have mood instability sounds like a tautology. Nonetheless, mood instability has particular relevance to BD: Many patients have irregular or labile moods even when they are between major episodes of mania and depression.¹

Children of parents with BD who have high levels of mood instability are at particularly high risk for developing BD (types I or II) in late adolescence or early adulthood.² The following case provides an illustration:

Patrick, age 14, entered treatment with diagnoses of ADHD and other specified bipolar disorder. His mother felt that his behavior resembled that of his father, who had been treated for manic episodes. During the COVID-19 pandemic, Patrick had become increasingly difficult at home, with significant oppositionality, impulsive behavior, and difficulty following through on school assignments or household tasks. His mother’s most significant complaints concerned Patrick’s sudden outbursts of anger and abrupt verbal abuse when she asked him to stop playing video games. When interrupted, he cursed loudly and sometimes turned violent; he had broken a window and a door at home and had on one occasion physically attacked his younger brother. Patrick agreed that he became angry at times, but felt that others provoked him. When queried about depression, he described anxiety and worry. He was unable to describe a particular trigger for his anxiety except for being interrupted in online games with his friends, which made him “feel like a total loser.”

His mother reported that Patrick had multiple 1- to 2-day intervals in which he became “really silly, laughing at nothing,” talking rapidly, jumping from one topic to another, and becoming annoyed when others didn’t share his enthusiasm. In these activated intervals, he slept little and seemed to be full of energy; his mother would hear him talking loudly into his phone throughout the night. During one such interval he had become verbally aggressive with a peer, which had ruined their friendship. Both Patrick and his mother reported that they had been fighting constantly and, in her words, “our house has become a war zone.”

In our recent article in the Journal of the American Academy of Child and Adolescent Psychiatry,³ my coauthors and I examined the association between parents’ ratings of mood instability and clinicians’ longitudinal ratings of symptoms and functioning among youth (ages 9-17 years) who were at high risk for BD. The participants met DSM-5 diagnostic criteria for major depressive disorder or other specified BD, defined as recurrent and brief periods of elevation and activation that did not meet syndromal mania or hypomania criteria. All participants had at least one first- or second-degree family member with a history of BD I or II. Following a period of evaluation, participants were randomly assigned to one of two 4-month psychological therapies: Family-focused therapy (12 sessions of psychoeducation, communication training, and problem-solving skills training) or enhanced usual care (6 sessions of family and individual psychoeducation and support). They also received pharmacological management from study-affiliated psychiatrists when warranted.

We measured mood instability at intake and every 4-6 months over an average of 2 years (range 0-255 weeks). We used a brief parent questionnaire – the Children’s Affective Lability Scale⁴ – which enables measurement of lability on the dimensions of elevation or activation (e.g., bursts of silliness or hilarity, excessive familiarity with others), irritability (e.g., temper outbursts), or anxious-depression (e.g., sudden bouts of crying).

Over the 1- to 4-year period of follow-up, mood instability was associated with poor prognosis indicators in high-risk youth: Being younger, having younger ages at first symptom onset, being diagnosed with other specified BD (vs. major depression), and having more complex patterns of comorbid disorders. Mood instability tracked closely with levels of mania, depression, and global functioning over the follow-up. There was a temporal pathway between a diagnosis of other specified bipolar disorder at intake and higher levels of mood instability at follow-up, which in turn predicted higher levels of parent/child conflict. High levels of mood lability may lead to isolation from peers and tension within family relationships, which may fuel further children’s expressions of frustration, rage, depression, or impulsive behavior.

Youth with higher levels of mood instability required more complex medication regimens over 1 year than did those with lower instability. There was an overall reduction in mood instability as children aged (or spent more time in treatment). Over the 1- to 4-year follow-up, family-focused therapy was associated with longer intervals prior to new mood episodes than was enhanced usual care, but reductions in mood instability were independent of the type of psychosocial treatment assigned to children.

The participants in this study could not be followed long enough to determine whether levels of mood instability were associated with the later development of syndromal BD. Other studies, however, have documented this relationship. Large-scale longitudinal studies of high-risk children find that measures of mood lability – along with early onset manic symptoms, depression, anxiety, and a family history of mania or hypomania – can be combined to calculate the risk that any individual child will develop BD I or II over the next 5-8 years.^2,5

Clinicians should include measurement of the severity and psychosocial determinants of persistent mood shifts in youth under their care, particularly those with a family history of BD. Mood instability is associated with more severe symptom trajectories, more social isolation, and greater distress and conflict within the family. It may require a greater intensity of both pharmacological and psychosocial treatments to treat existing symptoms and functional impairments, and to prevent further mood deterioration.

Dr. Miklowitz is Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior. He is the author of “The Bipolar Disorder Survival Guide, 3rd Ed.” (New York: Guilford Press, 2019) and “Bipolar Disorder: A Family-Focused Treatment Approach, 2nd Ed” (New York: Guilford Press, 2010). He has no conflicts of interest to disclose. Contact Dr. Miklowitz at dmiklowitz@mednet.ucla.edu.

References

1. Bonsall MB, et al. Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder. Proc Biol Sci. Mar 7 2012;279(1730):916-24. doi: 10.1098/rspb.2011.1246.

2. Hafeman DM, et al. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173(7):695-704. doi: 10.1176/appi.ajp.2015.15040414.

3. Miklowitz DJ, et al. Mood instability in youth at high risk for bipolar disorder. J Am Acad Child Adol Psychiatry. 2022 Mar 17;S0890-8567(22)00118-6. doi: 10.1016/j.jaac.2022.03.009.

4. Gerson AC, et al. The Children’s Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. Dec 20 1996;65(3):189-98. doi: 10.1016/s0165-1781(96)02851-x.

5. Birmaher B, et al. A risk calculator to predict the individual risk of conversion from subthreshold bipolar symptoms to bipolar disorder I or II in youth. J Am Acad Child Adol Psychiatry. 2018;57(10):755-63. doi: 10.1016/j.jaac.2018.05.023.

Mood instability, or sudden, unpredictable, and frequent shifts in emotional states, characterizes many types of psychiatric disorder, including attention-deficit/hyperactivity disorder (ADHD), personality disorders, depression, and posttraumatic stress disorder. To say that individuals with bipolar disorder (BD) have mood instability sounds like a tautology. Nonetheless, mood instability has particular relevance to BD: Many patients have irregular or labile moods even when they are between major episodes of mania and depression.¹

Children of parents with BD who have high levels of mood instability are at particularly high risk for developing BD (types I or II) in late adolescence or early adulthood.² The following case provides an illustration:

Patrick, age 14, entered treatment with diagnoses of ADHD and other specified bipolar disorder. His mother felt that his behavior resembled that of his father, who had been treated for manic episodes. During the COVID-19 pandemic, Patrick had become increasingly difficult at home, with significant oppositionality, impulsive behavior, and difficulty following through on school assignments or household tasks. His mother’s most significant complaints concerned Patrick’s sudden outbursts of anger and abrupt verbal abuse when she asked him to stop playing video games. When interrupted, he cursed loudly and sometimes turned violent; he had broken a window and a door at home and had on one occasion physically attacked his younger brother. Patrick agreed that he became angry at times, but felt that others provoked him. When queried about depression, he described anxiety and worry. He was unable to describe a particular trigger for his anxiety except for being interrupted in online games with his friends, which made him “feel like a total loser.”

His mother reported that Patrick had multiple 1- to 2-day intervals in which he became “really silly, laughing at nothing,” talking rapidly, jumping from one topic to another, and becoming annoyed when others didn’t share his enthusiasm. In these activated intervals, he slept little and seemed to be full of energy; his mother would hear him talking loudly into his phone throughout the night. During one such interval he had become verbally aggressive with a peer, which had ruined their friendship. Both Patrick and his mother reported that they had been fighting constantly and, in her words, “our house has become a war zone.”

In our recent article in the Journal of the American Academy of Child and Adolescent Psychiatry,³ my coauthors and I examined the association between parents’ ratings of mood instability and clinicians’ longitudinal ratings of symptoms and functioning among youth (ages 9-17 years) who were at high risk for BD. The participants met DSM-5 diagnostic criteria for major depressive disorder or other specified BD, defined as recurrent and brief periods of elevation and activation that did not meet syndromal mania or hypomania criteria. All participants had at least one first- or second-degree family member with a history of BD I or II. Following a period of evaluation, participants were randomly assigned to one of two 4-month psychological therapies: Family-focused therapy (12 sessions of psychoeducation, communication training, and problem-solving skills training) or enhanced usual care (6 sessions of family and individual psychoeducation and support). They also received pharmacological management from study-affiliated psychiatrists when warranted.

We measured mood instability at intake and every 4-6 months over an average of 2 years (range 0-255 weeks). We used a brief parent questionnaire – the Children’s Affective Lability Scale⁴ – which enables measurement of lability on the dimensions of elevation or activation (e.g., bursts of silliness or hilarity, excessive familiarity with others), irritability (e.g., temper outbursts), or anxious-depression (e.g., sudden bouts of crying).

Over the 1- to 4-year period of follow-up, mood instability was associated with poor prognosis indicators in high-risk youth: Being younger, having younger ages at first symptom onset, being diagnosed with other specified BD (vs. major depression), and having more complex patterns of comorbid disorders. Mood instability tracked closely with levels of mania, depression, and global functioning over the follow-up. There was a temporal pathway between a diagnosis of other specified bipolar disorder at intake and higher levels of mood instability at follow-up, which in turn predicted higher levels of parent/child conflict. High levels of mood lability may lead to isolation from peers and tension within family relationships, which may fuel further children’s expressions of frustration, rage, depression, or impulsive behavior.

Youth with higher levels of mood instability required more complex medication regimens over 1 year than did those with lower instability. There was an overall reduction in mood instability as children aged (or spent more time in treatment). Over the 1- to 4-year follow-up, family-focused therapy was associated with longer intervals prior to new mood episodes than was enhanced usual care, but reductions in mood instability were independent of the type of psychosocial treatment assigned to children.

The participants in this study could not be followed long enough to determine whether levels of mood instability were associated with the later development of syndromal BD. Other studies, however, have documented this relationship. Large-scale longitudinal studies of high-risk children find that measures of mood lability – along with early onset manic symptoms, depression, anxiety, and a family history of mania or hypomania – can be combined to calculate the risk that any individual child will develop BD I or II over the next 5-8 years.^2,5

Clinicians should include measurement of the severity and psychosocial determinants of persistent mood shifts in youth under their care, particularly those with a family history of BD. Mood instability is associated with more severe symptom trajectories, more social isolation, and greater distress and conflict within the family. It may require a greater intensity of both pharmacological and psychosocial treatments to treat existing symptoms and functional impairments, and to prevent further mood deterioration.

Dr. Miklowitz is Distinguished Professor of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Semel Institute for Neuroscience and Human Behavior. He is the author of “The Bipolar Disorder Survival Guide, 3rd Ed.” (New York: Guilford Press, 2019) and “Bipolar Disorder: A Family-Focused Treatment Approach, 2nd Ed” (New York: Guilford Press, 2010). He has no conflicts of interest to disclose. Contact Dr. Miklowitz at dmiklowitz@mednet.ucla.edu.

References

1. Bonsall MB, et al. Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder. Proc Biol Sci. Mar 7 2012;279(1730):916-24. doi: 10.1098/rspb.2011.1246.

2. Hafeman DM, et al. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorders in at-risk youths. Am J Psychiatry. 2016;173(7):695-704. doi: 10.1176/appi.ajp.2015.15040414.

3. Miklowitz DJ, et al. Mood instability in youth at high risk for bipolar disorder. J Am Acad Child Adol Psychiatry. 2022 Mar 17;S0890-8567(22)00118-6. doi: 10.1016/j.jaac.2022.03.009.

4. Gerson AC, et al. The Children’s Affective Lability Scale: a psychometric evaluation of reliability. Psychiatry Res. Dec 20 1996;65(3):189-98. doi: 10.1016/s0165-1781(96)02851-x.

5. Birmaher B, et al. A risk calculator to predict the individual risk of conversion from subthreshold bipolar symptoms to bipolar disorder I or II in youth. J Am Acad Child Adol Psychiatry. 2018;57(10):755-63. doi: 10.1016/j.jaac.2018.05.023.

Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.¹ Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.^2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.

Short Story Club

Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.⁴ In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.

Slowing Down

The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.⁵ The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.

Mirrors and Windows

Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.⁶ Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.

In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.⁷ The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.

The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.⁸ In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.

In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.⁹ She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.

Exploring the Taboo

A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.¹⁰ He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.

Moral Grounding

These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.¹¹ Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.

In another session we read and reflected on “Three Questions” by Leo Tolstoy.¹² In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.

Symbols and Metaphors

The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.¹³ The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.

Problem-solving Guide

A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.¹⁴ Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.

Bonding Through Shared Experience

The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.

Conclusions

Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.³ We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.³ We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.

This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.

Acknowledgments

The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.

Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.¹ Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.^2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.

Short Story Club

Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.⁴ In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.

Slowing Down

The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.⁵ The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.

Mirrors and Windows

Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.⁶ Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.

In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.⁷ The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.

The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.⁸ In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.

In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.⁹ She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.

Exploring the Taboo

A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.¹⁰ He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.

Moral Grounding

These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.¹¹ Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.

In another session we read and reflected on “Three Questions” by Leo Tolstoy.¹² In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.

Symbols and Metaphors

The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.¹³ The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.

Problem-solving Guide

A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.¹⁴ Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.

Bonding Through Shared Experience

The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.

Conclusions

Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.³ We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.³ We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.

This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.

Acknowledgments

The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.

Burnout and other forms of psychosocial distress are common among health care professionals necessitating measures to promote well-being and reduce burnout.¹ Studies have shown that nonmedical reading is associated with low burnout and that small group study sections can promote wellness.^2,3 Narrative medicine, which proposes a model for humane and effective medical practice, advocates for the necessity of narrative competence.

Short Story Club

Narrative competence is the ability to acknowledge, interpret, and act on the stories of others. The narrative skill of close reading also encourages reflective practice, equipping practitioners to better weather the tides of illness.⁴ In our case, we formed a short story club intervention to closely read, or read and reflect, on literary fiction. We explored how reading and reflecting would result in profound changes in thinking and feeling and noted different ways by which they can cause such well-being. We describe here the 7 ways in which stories led us to increase bonding, improve empathy, and promote meaning in medicine.

Slowing Down

The short story club helped to bond us together and increase our sense of meaning in medicine by slowing us down. One member of the group likened the experience to increasing the pixels in a painting, thereby improving the resolution and seeing more clearly. Another member mentioned the experience as a form of meditation in slowing down the brain, breathing in the story, and breathing out impressions. One story by Anatole Broyard emphasized the importance of slowing down and “brooding” over a patient.⁵ The author describes his experience as a prostate cancer patient, in which his body was treated but his story was ignored. He begged his doctors to pay more attention to his story to listen and to brood over him. This story was enlightening to us; we saw how desperate our patients are to tell their stories, and for us to hear their stories.

Mirrors and Windows

Another way reading and reflecting on short stories helped was by reflecting our practices to ourselves, as though looking into a mirror to see ourselves and out of a window to see others. We found that stories mirrored our own world and allowed us to discuss issues close to us without the embarrassment or stigma of owning the story. In one session we read “The Doctor’s Visit” by Anton Chekhov.⁶ Some of the members resonated with the doctor of this story who awkwardly attended to his lady patient whose son was dying of a brain tumor. The doctor was nervous, insecure, and unable to express any empathy. He was also the father of the child who was dying and refused to admit any responsibility. One member of the group stated that he could relate to the doctor’s insecurities and mentioned that he too felt insecure and even sometimes felt like an imposter. This led to a discussion of insecurities, ways to bolster self-confidence, and ways to accept and respect limitations. This was a conversation that may not have taken place without the story as anchor to discuss insecurities that we individually may not have been willing to admit to the group.

In a different session, we discussed the story “Interpreter of Maladies” by Jhumpa Lahiri in which a settled Indian American family returns to India to tour and learn about their heritage from a guide (the interpreter of maladies) who interpreted the culture for them.⁷ The family professed to be interested in knowing about the culture but could not concentrate: the wife stayed busy flirting with the guide and revealing outrageous secrets to him, the children were engrossed in their squabbles, and the father was essentially absent taking photographs as souvenirs instead of seeing the sites firsthand. Some of the members of the group were Indian American and could relate to the alienation from their home and nostalgia for their country, while others could relate to the same alienation, albeit from other cultures and countries. This allowed us to talk about deeply personal topics, without having to own the topic or reveal personal issues. The discussion led to a deep understanding and empathy for us and our colleagues knowing the pain of alienation that some of them felt but could not discuss.

The stories also served as windows into the world of others which enabled us to see and become the other. For example, in one session we reflected on “Babylon Revisited” by F. Scott Fitzgerald.⁸ In this story, an American man returns to Paris after the Great Depression and recalls his life as a young artist in the American artist expatriate community of Paris in the 1920s and 1930s. During that time, he partied, drank in excess, lost his wife to pneumonia (for which he was at least partially responsible), lost custody of his daughter, and lost his fortune. As he returned to Paris to try to reclaim his daughter, we feel his pain as he tries but fails to overcome chronic alcoholism, sexual indiscretions, and losses. This gave rise to discussion of losses in general as we became one with the main character. This increased our empathy for others in a way that could not have been possible without this short story as anchor.

In another session we reflected on “Hills Like White Elephants” by Ernest Hemingway, in which a man is waiting for a train while proposing his girlfriend get an abortion.⁹ She agonizes over her choices and makes no decision in this story. Yet, we the reader could “become” the woman in the story faced with hard choices of having a baby but losing the man she loves, or having an abortion and maybe losing him anyway. In becoming this woman, we could experience the complex emotions and feel an experience of the other.

Exploring the Taboo

A third aspect of the club was enabling discussion of controversial topics. There were topics that arose in the group which never would have arisen in clinical practice discussions. These had to do with the taboo topics such as romantic attachments to patients. We read “The Caves of Lascaux” and reflected on the story of a young doctor who becomes enamored and obsessed with his beautiful but dying patient.¹⁰ He becomes so obsessed with her that he almost abandons his wife, family, and stable livelihood to descend with her into the caves. This story gave rise to discussions about romantic attachment to patients and how to handle and extricate one from the situation. The senior doctors explained some of their relevant experiences and how they either transferred care or sought counseling to extricate themselves from a potentially dangerous situation, especially when they too fell under the spell of forbidden romance.

Moral Grounding

These sessions also served to define the moral basis of our own practice. Much of health care psychosocial distress is related to moral injury in which health care professionals do the wrong thing or fail to do the right thing at the right time, due to external pressures related to financial or other gains. Reading and reflecting put us face-to-face with moral dilemmas and let us find our moral grounding. In reading “The Haircut” by Ring Lardner, we explored the disruptive town scoundrel who harassed and tortured his friends and neighbors but in such outrageous ways that he was considered a comedian rather than an abuser.¹¹ Despite his hurtful acts, the townspeople (including the narrator) considered him a clown and laughed at his racist and sexist statements as well as his tricks.He faced no consequences such as confrontation, until the end when fate caught up. This story gave rise to a discussion of how we handle unkind, racist, sexist, or other comments which are disguised as humor, and to what extent we tolerate such controversial behavior. Do we go along with the scoundrel and laugh, or do we confront such people and insist that they respect and honor other people? The story sensitized the group to the ways in which prejudice and racism or sexism can be masked as humor, and to consider our moral responsibilities in society.

In another session we read and reflected on “Three Questions” by Leo Tolstoy.¹² In this story, a king travels to another territory but gets distracted by helping a neighbor in need, and thereby inadvertently and fortunately avoids the trap that had been devised to kill him. The author gives us his moral basis by asking and answering 3 questions: Who is the most important person? What is the most important thing to do? What is the most important thing to do now? His answers provided his moral grounding. We discussed our answers and the basis of our moral grounding, whether it be the injunction do no harm, the more complex religious backgrounds of our childhood, or otherwise.

Symbols and Metaphors

The practice of reading and reflecting also taught us symbols and metaphors. Symbols and metaphors are the essence of storytelling, and they provide keys to understanding people. We sought out and studied the metaphors and symbols in each of the stories we read. In “I Stood There Ironing”, a woman is ironing as she is being questioned by a social worker on the upbringing of her first daughter, and its impact on her psychosocial distress.¹³ The woman remembers the hardships in raising her daughter and her neglect and abuse of the child due to circumstances beyond her control. She keeps ironing back and forth as she recounts the ways in which she neglected her child. The ironing provides a metaphor for attempting to straighten out her life and for recognizing finally at the end of the story that the daughter should not be the dress, under which her iron is pressing. This gave rise to a discussion of metaphors in our lives and the meanings they carry.

Problem-solving Guide

A sixth way the reflections helped was by serving as a guide to solving our problems. Some of the stories we read resonated deeply with members of the group and provided guides to solving problems. In one meeting we discussed “Those Are as Brothers” by Nancy Hale, a story in which a Nazi concentration camp survivor finds refuge in a country home and develops a friendship with a survivor of an abusive marriage.¹⁴ Reading and reflecting on this story enabled us to see the impact of trauma on ourselves, our life choices, professions, ways of being, philosophies, and even on our next generation. The story was personal for several members of the group, some of whom were second-generation Holocaust survivors, and for one who admitted to severe trauma as a child. Discussing our backgrounds together, we empathized with each other and helped each other heal. The story also provided a guide to healing from trauma, as its title indicates: sharing stories together can be a way to heal. The solidarity of standing together, as brothers, heals. The concentration camp survivor was mistreated in his job, but the abuse trauma victim rushes to his defense and vows her friendship and support. This soothed his soul and healed his mind. The guidance is clear: we can do the same, find friends, treat them like brothers, support each other and heal.

Bonding Through Shared Experience

The final and possibly most important way in which the club helped was by serving as an adventure to bond group members together through shared experience. We believe that literature can capture imagination in extraordinary ways and provide an opportunity to undertake remarkable journeys. As such, together we traveled to the ends of the earth from the beginning to the end of time and beyond. We traveled through the hills of Africa, meandered in the streets of Russia and Poland, watched the racetracks in Italy, toured the Taj Mahal in India, and descended into the caves of Lascaux, all while working in Little Rock, Arkansas. We shared a wide array of experiences together, which allowed us to know ourselves and others better, to share stories, and to develop a common vision, common ground, and common culture.

Conclusions

Through reading and reflecting on stories, we bonded as a group, increased our empathy for each other and others, and found meaning in medicine. Other studies have shown that participation in small study groups promote physician well-being, improve job satisfaction, and decrease burnout.³ We synergized this effort by reading nonmedical stories on a consistent basis, hoping to gain resilience to psychosocial distress.³ We chose short stories rather than novels to minimize any stress from excess reading. Combining these interventions, small group studies and nonmedical reading, into a single intervention as is typical in the practice of narrative medicine may provide a way to improve team functioning.

This pilot study showed that it is possible to form short story clubs even in a busy oncology program and that such programs benefit participants in a variety of ways with no apparent adverse effects. Further research is needed to study the impact of reading and reflecting on medical work in small study groups in larger numbers of subjects and to evaluate their impact on burnout. Further study is also needed to develop narrative medicine curricula that best address the needs of particular subspecialties and to determine the optimal conditions for implementation.

Acknowledgments

The authors acknowledge Dr. Erick Messias for inspiring and encouraging this project at the University of Arkansas for Medical Sciences where he was Associate Dean for Faculty Affairs. He is presently Chair of Psychiatry and Behavioral Neuroscience at the St. Louis University School of Medicine, St. Louis, Missouri.

As a regular viewer of Jeopardy! I find it both interesting and educational. But the psychiatric neuroscientist in me marvels at the splendid cerebral attributes embedded in the brains of Jeopardy! champions.

Back in my college days, I participated in what were then called “general knowledge contests” and won a couple of trophies, the most gratifying of which was when our team of medical students beat the faculty team! Later, when my wife and I had children, Trivial Pursuit was a game frequently played in our household. So it is no wonder I have often thought of the remarkable, sometimes stunning intellectual performances of Jeopardy! champions.

What does it take to excel at Jeopardy!?

Watching contestants successfully answer a bewildering array of questions across an extensive spectrum of topics is simply dazzling and prompts me to ask: Which neurologic structures play a central role in the brains of Jeopardy! champions? So I channeled my inner neurobiologist and came up with the following prerequisites to excel at Jeopardy!:

• A hippocampus on steroids! Memory is obviously a core ingredient for responding to Jeopardy! questions. Unlike ordinary mortals, Jeopardy! champions appear to retain and instantaneously, accurately recall everything they have read, saw, or heard.
• A sublime network of dendritic spines, where learning is immediately transduced to biological memories, thanks to the wonders of experiential neuroplasticity in homo sapiens.
• A superlative frontal lobe, which provides the champion with an ultra-rapid abstraction ability in the dorsolateral prefrontal cortex, along with razor-sharp concentration and attention.
• An extremely well-myelinated network of the 137,000 miles of white mat­ter fibers in the human brain. This is what leads to fabulous processing speed. Rapid neurotransmission is impossible without very well-myelinated axons and dendrites. It is not enough for a Jeopardy! champion to know the answer and retrieve it from the hippocampus—they also must transmit the answer at lightning speed to the speech area, and then activate the motor area to enunciate the answer. Processing speed is the foundation of overall cognitive functioning.
• A first-rate Broca’s area, referred to as “the brain’s scriptwriter,” which shapes human speech. It receives the flow of sensory information from the temporal cortex, devises a plan for speaking, and passes that plan seamlessly to the motor cortex, which controls the movements of the mouth.
• Blistering speed reflexes to click the handheld response buzzer within a fraction of a millisecond after the host finishes reading the clue (not before, or a penalty is incurred). Jeopardy! champions always click the buzzer faster than their competitors, who may know the answer but have ordinary motor reflexes (also related to the degree of myelination and a motoric component of processing speed).
• A thick corpus callosum, the largest interhemispheric commissure, a bundle of 200 million white matter fibers connecting analogous regions in the right and left hemispheres, is vital for the rapid bidirectional transfer of bits of information from the intuitive/nonverbal right hemisphere to the mathematical/verbal left hemisphere, when the answer requires right hemispheric input.
• A bright occipital cortex and exceptional optic nerve and retina, so that champions can recognize faces or locations and read the questions before the host finishes reading them, which gives them an awesome edge on other contestants.

Obviously, the brains of Jeopardy! champions are a breed of their own, with exceptional performances by multiple regions converging to produce a winning performance. But during their childhood and youthful years, such brains also generate motivation, curiosity, and interest in a wide range of topics, from cultures, regions, music genres, and word games to history, geography, sports, science, medicine, astronomy, and Greek mythology.

Jeopardy! champions may appear to have regular jobs and ordinary lives, but they have resplendent “renaissance” brains. I wonder how they spent their childhood, who mentored them, what type of family lives they had, and what they dream of accomplishing other than winning on Jeopardy!. Will their awe-inspiring performance in Jeopardy! translate to overall success in life? That’s a story that remains to be told.

As a regular viewer of Jeopardy! I find it both interesting and educational. But the psychiatric neuroscientist in me marvels at the splendid cerebral attributes embedded in the brains of Jeopardy! champions.

Back in my college days, I participated in what were then called “general knowledge contests” and won a couple of trophies, the most gratifying of which was when our team of medical students beat the faculty team! Later, when my wife and I had children, Trivial Pursuit was a game frequently played in our household. So it is no wonder I have often thought of the remarkable, sometimes stunning intellectual performances of Jeopardy! champions.

What does it take to excel at Jeopardy!?

Watching contestants successfully answer a bewildering array of questions across an extensive spectrum of topics is simply dazzling and prompts me to ask: Which neurologic structures play a central role in the brains of Jeopardy! champions? So I channeled my inner neurobiologist and came up with the following prerequisites to excel at Jeopardy!:

• A hippocampus on steroids! Memory is obviously a core ingredient for responding to Jeopardy! questions. Unlike ordinary mortals, Jeopardy! champions appear to retain and instantaneously, accurately recall everything they have read, saw, or heard.
• A sublime network of dendritic spines, where learning is immediately transduced to biological memories, thanks to the wonders of experiential neuroplasticity in homo sapiens.
• A superlative frontal lobe, which provides the champion with an ultra-rapid abstraction ability in the dorsolateral prefrontal cortex, along with razor-sharp concentration and attention.
• An extremely well-myelinated network of the 137,000 miles of white mat­ter fibers in the human brain. This is what leads to fabulous processing speed. Rapid neurotransmission is impossible without very well-myelinated axons and dendrites. It is not enough for a Jeopardy! champion to know the answer and retrieve it from the hippocampus—they also must transmit the answer at lightning speed to the speech area, and then activate the motor area to enunciate the answer. Processing speed is the foundation of overall cognitive functioning.
• A first-rate Broca’s area, referred to as “the brain’s scriptwriter,” which shapes human speech. It receives the flow of sensory information from the temporal cortex, devises a plan for speaking, and passes that plan seamlessly to the motor cortex, which controls the movements of the mouth.
• Blistering speed reflexes to click the handheld response buzzer within a fraction of a millisecond after the host finishes reading the clue (not before, or a penalty is incurred). Jeopardy! champions always click the buzzer faster than their competitors, who may know the answer but have ordinary motor reflexes (also related to the degree of myelination and a motoric component of processing speed).
• A thick corpus callosum, the largest interhemispheric commissure, a bundle of 200 million white matter fibers connecting analogous regions in the right and left hemispheres, is vital for the rapid bidirectional transfer of bits of information from the intuitive/nonverbal right hemisphere to the mathematical/verbal left hemisphere, when the answer requires right hemispheric input.
• A bright occipital cortex and exceptional optic nerve and retina, so that champions can recognize faces or locations and read the questions before the host finishes reading them, which gives them an awesome edge on other contestants.

Obviously, the brains of Jeopardy! champions are a breed of their own, with exceptional performances by multiple regions converging to produce a winning performance. But during their childhood and youthful years, such brains also generate motivation, curiosity, and interest in a wide range of topics, from cultures, regions, music genres, and word games to history, geography, sports, science, medicine, astronomy, and Greek mythology.

Jeopardy! champions may appear to have regular jobs and ordinary lives, but they have resplendent “renaissance” brains. I wonder how they spent their childhood, who mentored them, what type of family lives they had, and what they dream of accomplishing other than winning on Jeopardy!. Will their awe-inspiring performance in Jeopardy! translate to overall success in life? That’s a story that remains to be told.

As a regular viewer of Jeopardy! I find it both interesting and educational. But the psychiatric neuroscientist in me marvels at the splendid cerebral attributes embedded in the brains of Jeopardy! champions.

Back in my college days, I participated in what were then called “general knowledge contests” and won a couple of trophies, the most gratifying of which was when our team of medical students beat the faculty team! Later, when my wife and I had children, Trivial Pursuit was a game frequently played in our household. So it is no wonder I have often thought of the remarkable, sometimes stunning intellectual performances of Jeopardy! champions.

What does it take to excel at Jeopardy!?

Watching contestants successfully answer a bewildering array of questions across an extensive spectrum of topics is simply dazzling and prompts me to ask: Which neurologic structures play a central role in the brains of Jeopardy! champions? So I channeled my inner neurobiologist and came up with the following prerequisites to excel at Jeopardy!:

• A hippocampus on steroids! Memory is obviously a core ingredient for responding to Jeopardy! questions. Unlike ordinary mortals, Jeopardy! champions appear to retain and instantaneously, accurately recall everything they have read, saw, or heard.
• A sublime network of dendritic spines, where learning is immediately transduced to biological memories, thanks to the wonders of experiential neuroplasticity in homo sapiens.
• A superlative frontal lobe, which provides the champion with an ultra-rapid abstraction ability in the dorsolateral prefrontal cortex, along with razor-sharp concentration and attention.
• An extremely well-myelinated network of the 137,000 miles of white mat­ter fibers in the human brain. This is what leads to fabulous processing speed. Rapid neurotransmission is impossible without very well-myelinated axons and dendrites. It is not enough for a Jeopardy! champion to know the answer and retrieve it from the hippocampus—they also must transmit the answer at lightning speed to the speech area, and then activate the motor area to enunciate the answer. Processing speed is the foundation of overall cognitive functioning.
• A first-rate Broca’s area, referred to as “the brain’s scriptwriter,” which shapes human speech. It receives the flow of sensory information from the temporal cortex, devises a plan for speaking, and passes that plan seamlessly to the motor cortex, which controls the movements of the mouth.
• Blistering speed reflexes to click the handheld response buzzer within a fraction of a millisecond after the host finishes reading the clue (not before, or a penalty is incurred). Jeopardy! champions always click the buzzer faster than their competitors, who may know the answer but have ordinary motor reflexes (also related to the degree of myelination and a motoric component of processing speed).
• A thick corpus callosum, the largest interhemispheric commissure, a bundle of 200 million white matter fibers connecting analogous regions in the right and left hemispheres, is vital for the rapid bidirectional transfer of bits of information from the intuitive/nonverbal right hemisphere to the mathematical/verbal left hemisphere, when the answer requires right hemispheric input.
• A bright occipital cortex and exceptional optic nerve and retina, so that champions can recognize faces or locations and read the questions before the host finishes reading them, which gives them an awesome edge on other contestants.

Obviously, the brains of Jeopardy! champions are a breed of their own, with exceptional performances by multiple regions converging to produce a winning performance. But during their childhood and youthful years, such brains also generate motivation, curiosity, and interest in a wide range of topics, from cultures, regions, music genres, and word games to history, geography, sports, science, medicine, astronomy, and Greek mythology.

Jeopardy! champions may appear to have regular jobs and ordinary lives, but they have resplendent “renaissance” brains. I wonder how they spent their childhood, who mentored them, what type of family lives they had, and what they dream of accomplishing other than winning on Jeopardy!. Will their awe-inspiring performance in Jeopardy! translate to overall success in life? That’s a story that remains to be told.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com .

Four years ago, pursuing a consultation-liaison psychiatry (CL) fellowship was the last thing on my mind. I had recently started my third year as a CL attending at the University of Cincinnati Medical Center and was becoming more of an integral part of its academic department. I felt that I had found my calling. I wanted to be an educator, with the hope of becoming a psychiatry residency program director. This idea was validated when I was awarded the Golden Apple for Excellence in Clinical Teaching, voted by the psychiatry residents, as well as a medical student teaching award. Both awards related to my CL duties.

And then, life happened. My wife and I decided to move east to be closer to family. I planned to continue my path at an academic institution while teaching CL psychiatry. Yet, each institution I interviewed with explained that while my recent experience was “great,” I would need to be formally CL fellowship–trained if I wanted to work in the CL division. On the one hand, this was frustrating to hear; however, the Accreditation Council for Graduate Medical Education has established rules regarding how many faculty at institutions that offer CL fellowships need to be CL fellowship–trained. After much consideration, specifically about my personal career aspirations and family situation, I decided to go “backwards” and pursue a CL fellowship.

Parts of the fellowship year were easier than the previous 3 years. For example, my caseload was much lighter, as were my supervision duties. However, almost immediately, there was an ego-check—for instance, recognizing that I would not always agree with my attendings, and other services would no longer view me as “the attending.” Despite that, as I now discuss with my trainees, I am never above further learning and gaining more clinical experience. Early in that first year of fellowship, I was involved in a complicated case of a patient with autoimmune encephalitis with severe catatonia who warranted electroconvulsive therapy. I gained experience using phenobarbital for the treatment of alcohol withdrawal, something I did not use during my residency or first 3 years as an attending.

Furthermore, my academic project that year was to revamp the fellowship. This included resetting the fellowship’s mission statement, as well as updating our rotations and curriculum, to better align with fellowship best practices around the country. It afforded me time to develop my own “educational” pathway and think of ways in which CL is expanding its footprint. Consistent with this, Park et al¹ demonstrated the most common “major reason” for pursuing a CL fellowship was to obtain clinical training; the “moderate reason” of teaching opportunities cannot be overlooked.

The value of a CL fellowship

CL is about the intersection of behavioral health with medicine. As such, I believe CL fellowships will be part of the solution for addressing the current health care cost crisis² as well as improving access to mental health treatment.³ We already see this solution in collaborative care programs. According to the National Resident Matching Program, in 2021 there were 60 CL fellowship programs and 124 CL fellowship positions offered nationwide, with a total of 89 fellowship applicants and 84 spots filled.⁴ Looking back 5 years, there were only 52 CL fellowship programs nationwide.⁴ While there are currently fewer applicants than spots, the fact that the number of available programs is increasing demonstrates the value that each institution puts into CL as well as the importance of our presence in the health care system. The CL fellowship year can create a special opportunity for the fellow that dovetails with their passions. If an applicant wants a program that has expert subspecialty services and focuses on teaching and social determinates of health, they can assuredly find that program.

The decision to pursue fellowship is a personal choice. I believe that CL as a subspecialty will demonstrate its importance to both the psychiatric and medical fields. CL fellowships can continue to innovate and move forward by recognizing the changing landscape of CL psychiatry and matching the fellowship experience to those needs. This will only make the draw for fellowship more powerful. Four years ago, I did not want to pursue fellowship—today I am truly grateful I did.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com .

Four years ago, pursuing a consultation-liaison psychiatry (CL) fellowship was the last thing on my mind. I had recently started my third year as a CL attending at the University of Cincinnati Medical Center and was becoming more of an integral part of its academic department. I felt that I had found my calling. I wanted to be an educator, with the hope of becoming a psychiatry residency program director. This idea was validated when I was awarded the Golden Apple for Excellence in Clinical Teaching, voted by the psychiatry residents, as well as a medical student teaching award. Both awards related to my CL duties.

And then, life happened. My wife and I decided to move east to be closer to family. I planned to continue my path at an academic institution while teaching CL psychiatry. Yet, each institution I interviewed with explained that while my recent experience was “great,” I would need to be formally CL fellowship–trained if I wanted to work in the CL division. On the one hand, this was frustrating to hear; however, the Accreditation Council for Graduate Medical Education has established rules regarding how many faculty at institutions that offer CL fellowships need to be CL fellowship–trained. After much consideration, specifically about my personal career aspirations and family situation, I decided to go “backwards” and pursue a CL fellowship.

Parts of the fellowship year were easier than the previous 3 years. For example, my caseload was much lighter, as were my supervision duties. However, almost immediately, there was an ego-check—for instance, recognizing that I would not always agree with my attendings, and other services would no longer view me as “the attending.” Despite that, as I now discuss with my trainees, I am never above further learning and gaining more clinical experience. Early in that first year of fellowship, I was involved in a complicated case of a patient with autoimmune encephalitis with severe catatonia who warranted electroconvulsive therapy. I gained experience using phenobarbital for the treatment of alcohol withdrawal, something I did not use during my residency or first 3 years as an attending.

Furthermore, my academic project that year was to revamp the fellowship. This included resetting the fellowship’s mission statement, as well as updating our rotations and curriculum, to better align with fellowship best practices around the country. It afforded me time to develop my own “educational” pathway and think of ways in which CL is expanding its footprint. Consistent with this, Park et al¹ demonstrated the most common “major reason” for pursuing a CL fellowship was to obtain clinical training; the “moderate reason” of teaching opportunities cannot be overlooked.

The value of a CL fellowship

CL is about the intersection of behavioral health with medicine. As such, I believe CL fellowships will be part of the solution for addressing the current health care cost crisis² as well as improving access to mental health treatment.³ We already see this solution in collaborative care programs. According to the National Resident Matching Program, in 2021 there were 60 CL fellowship programs and 124 CL fellowship positions offered nationwide, with a total of 89 fellowship applicants and 84 spots filled.⁴ Looking back 5 years, there were only 52 CL fellowship programs nationwide.⁴ While there are currently fewer applicants than spots, the fact that the number of available programs is increasing demonstrates the value that each institution puts into CL as well as the importance of our presence in the health care system. The CL fellowship year can create a special opportunity for the fellow that dovetails with their passions. If an applicant wants a program that has expert subspecialty services and focuses on teaching and social determinates of health, they can assuredly find that program.

The decision to pursue fellowship is a personal choice. I believe that CL as a subspecialty will demonstrate its importance to both the psychiatric and medical fields. CL fellowships can continue to innovate and move forward by recognizing the changing landscape of CL psychiatry and matching the fellowship experience to those needs. This will only make the draw for fellowship more powerful. Four years ago, I did not want to pursue fellowship—today I am truly grateful I did.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com .

Four years ago, pursuing a consultation-liaison psychiatry (CL) fellowship was the last thing on my mind. I had recently started my third year as a CL attending at the University of Cincinnati Medical Center and was becoming more of an integral part of its academic department. I felt that I had found my calling. I wanted to be an educator, with the hope of becoming a psychiatry residency program director. This idea was validated when I was awarded the Golden Apple for Excellence in Clinical Teaching, voted by the psychiatry residents, as well as a medical student teaching award. Both awards related to my CL duties.

And then, life happened. My wife and I decided to move east to be closer to family. I planned to continue my path at an academic institution while teaching CL psychiatry. Yet, each institution I interviewed with explained that while my recent experience was “great,” I would need to be formally CL fellowship–trained if I wanted to work in the CL division. On the one hand, this was frustrating to hear; however, the Accreditation Council for Graduate Medical Education has established rules regarding how many faculty at institutions that offer CL fellowships need to be CL fellowship–trained. After much consideration, specifically about my personal career aspirations and family situation, I decided to go “backwards” and pursue a CL fellowship.

Parts of the fellowship year were easier than the previous 3 years. For example, my caseload was much lighter, as were my supervision duties. However, almost immediately, there was an ego-check—for instance, recognizing that I would not always agree with my attendings, and other services would no longer view me as “the attending.” Despite that, as I now discuss with my trainees, I am never above further learning and gaining more clinical experience. Early in that first year of fellowship, I was involved in a complicated case of a patient with autoimmune encephalitis with severe catatonia who warranted electroconvulsive therapy. I gained experience using phenobarbital for the treatment of alcohol withdrawal, something I did not use during my residency or first 3 years as an attending.

Furthermore, my academic project that year was to revamp the fellowship. This included resetting the fellowship’s mission statement, as well as updating our rotations and curriculum, to better align with fellowship best practices around the country. It afforded me time to develop my own “educational” pathway and think of ways in which CL is expanding its footprint. Consistent with this, Park et al¹ demonstrated the most common “major reason” for pursuing a CL fellowship was to obtain clinical training; the “moderate reason” of teaching opportunities cannot be overlooked.

The value of a CL fellowship

CL is about the intersection of behavioral health with medicine. As such, I believe CL fellowships will be part of the solution for addressing the current health care cost crisis² as well as improving access to mental health treatment.³ We already see this solution in collaborative care programs. According to the National Resident Matching Program, in 2021 there were 60 CL fellowship programs and 124 CL fellowship positions offered nationwide, with a total of 89 fellowship applicants and 84 spots filled.⁴ Looking back 5 years, there were only 52 CL fellowship programs nationwide.⁴ While there are currently fewer applicants than spots, the fact that the number of available programs is increasing demonstrates the value that each institution puts into CL as well as the importance of our presence in the health care system. The CL fellowship year can create a special opportunity for the fellow that dovetails with their passions. If an applicant wants a program that has expert subspecialty services and focuses on teaching and social determinates of health, they can assuredly find that program.

The decision to pursue fellowship is a personal choice. I believe that CL as a subspecialty will demonstrate its importance to both the psychiatric and medical fields. CL fellowships can continue to innovate and move forward by recognizing the changing landscape of CL psychiatry and matching the fellowship experience to those needs. This will only make the draw for fellowship more powerful. Four years ago, I did not want to pursue fellowship—today I am truly grateful I did.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

As we see the end of the COVID-19 era through a collective windshield, there is hope and optimism at the exit ramps ahead of us. This unforeseen era has brought not only unprecedented change to the practice of medicine, but also a resurgent focus on the impact of medical care. The rapid adoption of telemedicine, the medical heroism lauded in the press during the early days of the pandemic, and the subsequent psychosocial impact of quarantines and lockdowns have brought increased attention to our citizens’ mental health, and not just during a crisis, but in a more holistic sense.

In fact, with the most recent annual Presidential State of the Union Address, mental health has finally received an invitation to the national agenda.  This is an admirable achievement, a nod from Uncle Sam that says, “Here’s your seat at the table.” Now that we have earned this seat, have we improved our understanding of mental illness, treatment options, and our access to them? Or have we lost sight of our real challenges? Shouldn’t achieving national prominence have resulted in newfound treatments and strategies to increase access and understanding?

Instead, we are still touting the same (although perhaps nuanced) monoamine hypothesis underlying most of our conditions, as we have for decades.  Vast areas of the country are out of reach of a local psychiatrist. Our treatments, largely centered on medications, though hopeful and promising at times, would fall short of the hurdle to become mainstay treatments in other medical specialties. Of course, the counterpoints are obvious: there are novel treatments (eg, ketamine, transcranial magnetic stimulation) and new understandings of glutamate and gamma aminobutyric acid systems in mood regulation and addiction. We also can use telemedicine to improve access to psychiatric care in underserved areas. But the overarching truth remains: an understanding of psychiatric illnesses, specifically the pathophysiology underlying those conditions, remains elusive or partially understood. Until we have a pathophysiology to treat, we can only continue to describe phenomenology and treat symptomatology.

Since we are treating symptoms, we must rely on verbal descriptions of psychiatric conditions. Descriptions and discussions of mental illness have pervaded the airwaves and media. It is not uncommon or unusual to hear people talk about depression, anxiety, insomnia, addiction, or even psychosis in a very normal, unjarring way.  These words, which represent severe medical conditions, have now become part of the national nosology and colloquial description of individuals’ day-to-day lives.  Have we stripped the severity and seriousness of our conditions from their descriptors in order to increase awareness and make mental health care a more “normal” part of health care?

We see it in clinics, the media, our schools, and our workplaces. Children and teens are talking about social anxiety because they feel a bit nervous on stage as their part in a school play begins. Teens are asking for extra time on a difficult test in a challenging class that is supposed to be strenuous. Employees are asking for mental health leave when a demanding new boss arrives on the scene.

Has our own campaign to increase awareness and destigmatize mental illness caused it to become diluted? Have we raised awareness by diluting its severity and seriousness, by making our nosology equivalent to everyday stressors? Was this a marketing strategy, a failure of our own nosology, or an inadvertent fallout of a decades-long campaign to raise mental health awareness?

Continue to: Until we have clear...

Until we have clear, delineated pathophysiology to treat, we will remain wed to our descriptive nosology. This nosology is flawed, at times ambiguous and overlapping, and now has become diluted to be more palatable to a national and consumer audience.  

So yes, let’s grab a chair at the national table, but let’s make sure we’re not just chairwarmers. It’s time we redouble our focus on unraveling the pathophysiology of psychiatric illnesses, and to focus on a new scientific nosology, as opposed to our current, almost colloquial and now diluted descriptors that may raise awareness but do little to advance a real understanding of mental illness.  A more holistic understanding of the pathophysiology of psychiatric disorders may provide us with a more scientific nosology. Ultimately, we can hope for more effective, and perhaps even curative treatments. That, my colleagues, is what will give us not just a seat at the table, but maybe even a table of our own.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

As we see the end of the COVID-19 era through a collective windshield, there is hope and optimism at the exit ramps ahead of us. This unforeseen era has brought not only unprecedented change to the practice of medicine, but also a resurgent focus on the impact of medical care. The rapid adoption of telemedicine, the medical heroism lauded in the press during the early days of the pandemic, and the subsequent psychosocial impact of quarantines and lockdowns have brought increased attention to our citizens’ mental health, and not just during a crisis, but in a more holistic sense.

In fact, with the most recent annual Presidential State of the Union Address, mental health has finally received an invitation to the national agenda.  This is an admirable achievement, a nod from Uncle Sam that says, “Here’s your seat at the table.” Now that we have earned this seat, have we improved our understanding of mental illness, treatment options, and our access to them? Or have we lost sight of our real challenges? Shouldn’t achieving national prominence have resulted in newfound treatments and strategies to increase access and understanding?

Instead, we are still touting the same (although perhaps nuanced) monoamine hypothesis underlying most of our conditions, as we have for decades.  Vast areas of the country are out of reach of a local psychiatrist. Our treatments, largely centered on medications, though hopeful and promising at times, would fall short of the hurdle to become mainstay treatments in other medical specialties. Of course, the counterpoints are obvious: there are novel treatments (eg, ketamine, transcranial magnetic stimulation) and new understandings of glutamate and gamma aminobutyric acid systems in mood regulation and addiction. We also can use telemedicine to improve access to psychiatric care in underserved areas. But the overarching truth remains: an understanding of psychiatric illnesses, specifically the pathophysiology underlying those conditions, remains elusive or partially understood. Until we have a pathophysiology to treat, we can only continue to describe phenomenology and treat symptomatology.

Since we are treating symptoms, we must rely on verbal descriptions of psychiatric conditions. Descriptions and discussions of mental illness have pervaded the airwaves and media. It is not uncommon or unusual to hear people talk about depression, anxiety, insomnia, addiction, or even psychosis in a very normal, unjarring way.  These words, which represent severe medical conditions, have now become part of the national nosology and colloquial description of individuals’ day-to-day lives.  Have we stripped the severity and seriousness of our conditions from their descriptors in order to increase awareness and make mental health care a more “normal” part of health care?

We see it in clinics, the media, our schools, and our workplaces. Children and teens are talking about social anxiety because they feel a bit nervous on stage as their part in a school play begins. Teens are asking for extra time on a difficult test in a challenging class that is supposed to be strenuous. Employees are asking for mental health leave when a demanding new boss arrives on the scene.

Has our own campaign to increase awareness and destigmatize mental illness caused it to become diluted? Have we raised awareness by diluting its severity and seriousness, by making our nosology equivalent to everyday stressors? Was this a marketing strategy, a failure of our own nosology, or an inadvertent fallout of a decades-long campaign to raise mental health awareness?

Continue to: Until we have clear...

Until we have clear, delineated pathophysiology to treat, we will remain wed to our descriptive nosology. This nosology is flawed, at times ambiguous and overlapping, and now has become diluted to be more palatable to a national and consumer audience.  

So yes, let’s grab a chair at the national table, but let’s make sure we’re not just chairwarmers. It’s time we redouble our focus on unraveling the pathophysiology of psychiatric illnesses, and to focus on a new scientific nosology, as opposed to our current, almost colloquial and now diluted descriptors that may raise awareness but do little to advance a real understanding of mental illness.  A more holistic understanding of the pathophysiology of psychiatric disorders may provide us with a more scientific nosology. Ultimately, we can hope for more effective, and perhaps even curative treatments. That, my colleagues, is what will give us not just a seat at the table, but maybe even a table of our own.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style. For more information, contact letters@currentpsychiatry.com.

As we see the end of the COVID-19 era through a collective windshield, there is hope and optimism at the exit ramps ahead of us. This unforeseen era has brought not only unprecedented change to the practice of medicine, but also a resurgent focus on the impact of medical care. The rapid adoption of telemedicine, the medical heroism lauded in the press during the early days of the pandemic, and the subsequent psychosocial impact of quarantines and lockdowns have brought increased attention to our citizens’ mental health, and not just during a crisis, but in a more holistic sense.

In fact, with the most recent annual Presidential State of the Union Address, mental health has finally received an invitation to the national agenda.  This is an admirable achievement, a nod from Uncle Sam that says, “Here’s your seat at the table.” Now that we have earned this seat, have we improved our understanding of mental illness, treatment options, and our access to them? Or have we lost sight of our real challenges? Shouldn’t achieving national prominence have resulted in newfound treatments and strategies to increase access and understanding?

Instead, we are still touting the same (although perhaps nuanced) monoamine hypothesis underlying most of our conditions, as we have for decades.  Vast areas of the country are out of reach of a local psychiatrist. Our treatments, largely centered on medications, though hopeful and promising at times, would fall short of the hurdle to become mainstay treatments in other medical specialties. Of course, the counterpoints are obvious: there are novel treatments (eg, ketamine, transcranial magnetic stimulation) and new understandings of glutamate and gamma aminobutyric acid systems in mood regulation and addiction. We also can use telemedicine to improve access to psychiatric care in underserved areas. But the overarching truth remains: an understanding of psychiatric illnesses, specifically the pathophysiology underlying those conditions, remains elusive or partially understood. Until we have a pathophysiology to treat, we can only continue to describe phenomenology and treat symptomatology.

Since we are treating symptoms, we must rely on verbal descriptions of psychiatric conditions. Descriptions and discussions of mental illness have pervaded the airwaves and media. It is not uncommon or unusual to hear people talk about depression, anxiety, insomnia, addiction, or even psychosis in a very normal, unjarring way.  These words, which represent severe medical conditions, have now become part of the national nosology and colloquial description of individuals’ day-to-day lives.  Have we stripped the severity and seriousness of our conditions from their descriptors in order to increase awareness and make mental health care a more “normal” part of health care?

We see it in clinics, the media, our schools, and our workplaces. Children and teens are talking about social anxiety because they feel a bit nervous on stage as their part in a school play begins. Teens are asking for extra time on a difficult test in a challenging class that is supposed to be strenuous. Employees are asking for mental health leave when a demanding new boss arrives on the scene.

Has our own campaign to increase awareness and destigmatize mental illness caused it to become diluted? Have we raised awareness by diluting its severity and seriousness, by making our nosology equivalent to everyday stressors? Was this a marketing strategy, a failure of our own nosology, or an inadvertent fallout of a decades-long campaign to raise mental health awareness?

Continue to: Until we have clear...

Until we have clear, delineated pathophysiology to treat, we will remain wed to our descriptive nosology. This nosology is flawed, at times ambiguous and overlapping, and now has become diluted to be more palatable to a national and consumer audience.  

So yes, let’s grab a chair at the national table, but let’s make sure we’re not just chairwarmers. It’s time we redouble our focus on unraveling the pathophysiology of psychiatric illnesses, and to focus on a new scientific nosology, as opposed to our current, almost colloquial and now diluted descriptors that may raise awareness but do little to advance a real understanding of mental illness.  A more holistic understanding of the pathophysiology of psychiatric disorders may provide us with a more scientific nosology. Ultimately, we can hope for more effective, and perhaps even curative treatments. That, my colleagues, is what will give us not just a seat at the table, but maybe even a table of our own.