Commentary

COVID has changed our world very rapidly. There are good changes, such as cleaner air and the ability to use telehealth widely. But there are devastating changes. As we are all aware, we have lost more than 400,000 people in America, and that number is climbing.

How can we mitigate some of the psychological effects of the pandemic? It is time to bring lessons learned on the battlefield to civilian psychiatrists and health care systems.

Despite having participated in mass casualty drills, no health system was trained or psychologically prepared for this once-in-a-century event.

The military dictum, “train like you fight; fight like you train” falls short considering the speed of viral replication, the serious flaws and disparities in our health care system revealed by COVID-19, and the public’s disturbingly variable adherence to preventive measures.

Like combat troops, health care workers put the needs of others ahead of their own. They suck up strain and step back from their own needs in favor of the mission.

Whether in combat or pandemic, leaders have valuable opportunities to promote the effectiveness of those on the front lines by caring for them. Those in charge may, themselves, be profoundly affected. While other team members focus on defined roles, leaders are forced to deal with many unknowns. They must often act without adequate information or resources.

Some of us have worked at hospitals treating many COVID patients and have been on “the front lines” for almost a year. We are asked a lot of questions, to which we often answer, "I don't know" or "there are no good choices."

All leaders work hard to model strength, but a difficult lesson that the military has had to learn is that leaders may strengthen cohesion by showing their grief, modeling self-care, drawing attention to even small successes in the face of overwhelming loss, and, when necessary, finding words for those losses.

Peer support is particularly important in high-stress situations. Mental health providers are uniquely qualified to share information, pick up on signs of severe stress, and provide support at the point of need.

Military combat stress control doctrine does, however, provide best practices that can be implemented across civilian health care systems. Its key elements are:

• Confidence in leadership at all levels – requiring visibility (“battlespace circulation”) of leaders who listen and share timely, accurate information.
• Realistic training – especially for those who, because of staff shortages, assume unfamiliar duties.
• Self-care – including regular meals, adequate sleep, and ongoing contact with family and friends. Here of course, the contact should be virtual as much as possible.
• Belief in the Mission – compassion satisfaction is a buffer against burnout.
• Esprit de corps – cohesive teams suffer significantly fewer combat stress casualties.

It is true that these principles have more often been tested in short-term crisis rather than the long slog that is COVID-19. This pandemic is more like an ongoing civil war than a distant battlefield because your home and those close to you share the risk.

There is no easy path ahead for America’s civilian health care system. These military principles, tested under fire, offer valuable opportunities in the ongoing battle against COVID-19.

Dr. Ritchie practices psychiatry in Washington. She has no disclosures.

Dr. Kudler is associate consulting professor of psychiatry and behavioral sciences at Duke University in Durham. N.C., and recently retired from his post as chief consultant for mental health, at the Department of Veterans Affairs. He has no relevant financial relationships.

Dr. Yehuda is professor of psychiatry and neuroscience and director of the traumatic stress studies division at the Mount Sinai School of Medicine, New York. She also serves as director of mental health at the James J. Peters Veterans Affairs Medical Center, also in New York. Dr. Yehuda has no disclosures.

Dr. Koffman is the senior consultant for Integrative Medicine & Behavioral Health at the National Intrepid Center of Excellence, Bethesda, Md. He has no disclosures.

COVID has changed our world very rapidly. There are good changes, such as cleaner air and the ability to use telehealth widely. But there are devastating changes. As we are all aware, we have lost more than 400,000 people in America, and that number is climbing.

How can we mitigate some of the psychological effects of the pandemic? It is time to bring lessons learned on the battlefield to civilian psychiatrists and health care systems.

Despite having participated in mass casualty drills, no health system was trained or psychologically prepared for this once-in-a-century event.

The military dictum, “train like you fight; fight like you train” falls short considering the speed of viral replication, the serious flaws and disparities in our health care system revealed by COVID-19, and the public’s disturbingly variable adherence to preventive measures.

Like combat troops, health care workers put the needs of others ahead of their own. They suck up strain and step back from their own needs in favor of the mission.

Whether in combat or pandemic, leaders have valuable opportunities to promote the effectiveness of those on the front lines by caring for them. Those in charge may, themselves, be profoundly affected. While other team members focus on defined roles, leaders are forced to deal with many unknowns. They must often act without adequate information or resources.

Some of us have worked at hospitals treating many COVID patients and have been on “the front lines” for almost a year. We are asked a lot of questions, to which we often answer, "I don't know" or "there are no good choices."

All leaders work hard to model strength, but a difficult lesson that the military has had to learn is that leaders may strengthen cohesion by showing their grief, modeling self-care, drawing attention to even small successes in the face of overwhelming loss, and, when necessary, finding words for those losses.

Peer support is particularly important in high-stress situations. Mental health providers are uniquely qualified to share information, pick up on signs of severe stress, and provide support at the point of need.

Military combat stress control doctrine does, however, provide best practices that can be implemented across civilian health care systems. Its key elements are:

• Confidence in leadership at all levels – requiring visibility (“battlespace circulation”) of leaders who listen and share timely, accurate information.
• Realistic training – especially for those who, because of staff shortages, assume unfamiliar duties.
• Self-care – including regular meals, adequate sleep, and ongoing contact with family and friends. Here of course, the contact should be virtual as much as possible.
• Belief in the Mission – compassion satisfaction is a buffer against burnout.
• Esprit de corps – cohesive teams suffer significantly fewer combat stress casualties.

It is true that these principles have more often been tested in short-term crisis rather than the long slog that is COVID-19. This pandemic is more like an ongoing civil war than a distant battlefield because your home and those close to you share the risk.

There is no easy path ahead for America’s civilian health care system. These military principles, tested under fire, offer valuable opportunities in the ongoing battle against COVID-19.

Dr. Ritchie practices psychiatry in Washington. She has no disclosures.

Dr. Kudler is associate consulting professor of psychiatry and behavioral sciences at Duke University in Durham. N.C., and recently retired from his post as chief consultant for mental health, at the Department of Veterans Affairs. He has no relevant financial relationships.

Dr. Yehuda is professor of psychiatry and neuroscience and director of the traumatic stress studies division at the Mount Sinai School of Medicine, New York. She also serves as director of mental health at the James J. Peters Veterans Affairs Medical Center, also in New York. Dr. Yehuda has no disclosures.

Dr. Koffman is the senior consultant for Integrative Medicine & Behavioral Health at the National Intrepid Center of Excellence, Bethesda, Md. He has no disclosures.

COVID has changed our world very rapidly. There are good changes, such as cleaner air and the ability to use telehealth widely. But there are devastating changes. As we are all aware, we have lost more than 400,000 people in America, and that number is climbing.

How can we mitigate some of the psychological effects of the pandemic? It is time to bring lessons learned on the battlefield to civilian psychiatrists and health care systems.

Despite having participated in mass casualty drills, no health system was trained or psychologically prepared for this once-in-a-century event.

The military dictum, “train like you fight; fight like you train” falls short considering the speed of viral replication, the serious flaws and disparities in our health care system revealed by COVID-19, and the public’s disturbingly variable adherence to preventive measures.

Like combat troops, health care workers put the needs of others ahead of their own. They suck up strain and step back from their own needs in favor of the mission.

Whether in combat or pandemic, leaders have valuable opportunities to promote the effectiveness of those on the front lines by caring for them. Those in charge may, themselves, be profoundly affected. While other team members focus on defined roles, leaders are forced to deal with many unknowns. They must often act without adequate information or resources.

Some of us have worked at hospitals treating many COVID patients and have been on “the front lines” for almost a year. We are asked a lot of questions, to which we often answer, "I don't know" or "there are no good choices."

All leaders work hard to model strength, but a difficult lesson that the military has had to learn is that leaders may strengthen cohesion by showing their grief, modeling self-care, drawing attention to even small successes in the face of overwhelming loss, and, when necessary, finding words for those losses.

Peer support is particularly important in high-stress situations. Mental health providers are uniquely qualified to share information, pick up on signs of severe stress, and provide support at the point of need.

Military combat stress control doctrine does, however, provide best practices that can be implemented across civilian health care systems. Its key elements are:

• Confidence in leadership at all levels – requiring visibility (“battlespace circulation”) of leaders who listen and share timely, accurate information.
• Realistic training – especially for those who, because of staff shortages, assume unfamiliar duties.
• Self-care – including regular meals, adequate sleep, and ongoing contact with family and friends. Here of course, the contact should be virtual as much as possible.
• Belief in the Mission – compassion satisfaction is a buffer against burnout.
• Esprit de corps – cohesive teams suffer significantly fewer combat stress casualties.

It is true that these principles have more often been tested in short-term crisis rather than the long slog that is COVID-19. This pandemic is more like an ongoing civil war than a distant battlefield because your home and those close to you share the risk.

There is no easy path ahead for America’s civilian health care system. These military principles, tested under fire, offer valuable opportunities in the ongoing battle against COVID-19.

Dr. Ritchie practices psychiatry in Washington. She has no disclosures.

Dr. Kudler is associate consulting professor of psychiatry and behavioral sciences at Duke University in Durham. N.C., and recently retired from his post as chief consultant for mental health, at the Department of Veterans Affairs. He has no relevant financial relationships.

Dr. Yehuda is professor of psychiatry and neuroscience and director of the traumatic stress studies division at the Mount Sinai School of Medicine, New York. She also serves as director of mental health at the James J. Peters Veterans Affairs Medical Center, also in New York. Dr. Yehuda has no disclosures.

Dr. Koffman is the senior consultant for Integrative Medicine & Behavioral Health at the National Intrepid Center of Excellence, Bethesda, Md. He has no disclosures.

During the ongoing COVID-19 pandemic, many people are spending endless hours at home looking at computer, phone, and television screens. Our population has turned to Internet use and television watching as a coping mechanism to deal with their isolation, boredom, stress, and fear of the virus. Indeed, some people have become addicted to watching television and binge-watching entire series in a single sitting on subscription streaming services.

A U.K. study showed that, during the lockdown, adults averaged spending 40% of their waking hours in front of a screen. After a long binge-watch, folks often forget what happened in the episodes or even the name of the program they viewed. When someone finds himself in this situation and can’t remember very much about what he actually watched, he feels as though he has wasted his own time and might become dysphoric and depressed. This type of viewer feels disconnected and forgets what he watched because he is experiencing passive enjoyment, rather than actively relating to the world.

So should television binge-watching give people feelings of guilt?

Fortunately, there are some positive factors about spending excessive time engrossed in these screens during a pandemic; some people use television viewing as a coping mechanism to deal with the reality and the fear of the coronavirus. Some beneficial aspects of television watching include:

• Escaping from the reality and stress of the pandemic in an emotionally safe, isolated cocoon.
• Experiencing safety from contracting COVID-19 by sheltering in place, isolating, and physical distancing from other people in the outside world.
• Experiencing a subdued, private, and mentally relaxing environment.
• Being productive and multitasking while watching television, for example, knit, sew, fold clothes, pay bills, write a letter, etc.

Despite many beneficial aspects of excessive television watching during the pandemic, we have to ask: Can too much television prove detrimental to our mental or physical well-being?
 

Associated mental, and physical problems

Cause and effect between excessive screen time and sleep disturbances is scientifically unproven, but there is an association between those factors.

Excessive screen time is associated with a sleep deficit, and a proper amount of sleep is necessary for optimal brain function, a healthy immune system, good memory, and overall well-being. Sleep cleans out the short-term memory stage from the information learned that day to make room for new memories. This allows us to store memories every day. An inadequate amount of sleep causes memory problems and cognitive deficits because we are not storing as many memories from days when we are sleep deprived. A good night’s sleep will prevent stress from one day to be carried over to the next day.

Lack of sleep affects people differently, but in some cases, a shortage of sleep can cause feelings of depression and isolation. Television, computer, and phone screens convey excessive damaging LED and blue light, detrimentally affecting our melatonin production and circadian rhythm. Blue light has wavelengths between 380 nm and 500 nm, and although blue wavelengths are beneficial in the day and increase positive mental mood, attention, and reaction times, blue wavelengths are destructive at night. Blue-light exposure suppresses the secretion of melatonin, which, as we know, is a hormone that influences circadian rhythms. The negative disruption of circadian rhythm throws the body’s biological clock in disarray and makes it more difficult for the mind to shut down at night.

Unfortunately, electronics with LED screens increase the amount of exposure to these blue wavelengths. In addition, the U.S. National Toxicology Program has suggested that a link exists between blue-light exposure at night to diabetes, heart disease, cancer, and obesity (Sci Tot Environ. 2017 Dec 31;[607-8]:1073-84).
 

Advice for patients and clinicians

Time spent watching television and using the Internet should be done in moderation. Make sure that patients understand that they should not feel guilty about watching television during these periods of isolation.

Encourage patients to be selective in their television viewing and to research available programs on streaming services and TV – and limit their screen time only to programs that truly interest them. Discourage them from watching television endlessly, hour after hour. Also, discourage patients from watching too much news. Instead, tell them to limit news to 1 hour per day, because news they perceive as bad might increase their overall anxiety.

Tell patients to engage in physical exercise every day; walk or run outside if possible. When inside, advise them to get up and walk around at least once per hour. Other advice we would like to offer patients and clinicians alike are:

• Put yourself on a schedule and go to sleep the same time each night and try to get 8 hours of sleep in a 24-hour period.
• Put away your devices 1 hour before going to bed or at least use dark mode, and wear blue-block glasses, since they are easier on the eyes and brain. Do not use television to put yourself to sleep. Spending too much time reading news stories is not a good idea, either, because doing so is mentally stimulating and can cause more uncertainty – making it difficult to sleep.
• Protect your eye health by purchasing and installing light bulbs with more internal red coating than blue. These bulbs will produce a warmer tone than the blue, and warmer tones will be less likely to shift circadian rhythm and suppress melatonin, thus reducing blue-light exposure. Blink your eyes often, and use eye solution for dry eyes.
• Sleep in total darkness to reduce your exposure to blue light. Take supplements with lutein and zeaxanthin, which may reduce the oxidative effects of blue light.

Encouraging patients to follow these guidelines – and adhering to them ourselves – should help us emerge from the COVID-19 pandemic mentally and physically healthy.

Dr. Cohen is board certified in psychiatry and has had a private practice in Philadelphia for more than 35 years. His areas of specialty include sports psychiatry, agoraphobia, depression, and substance abuse. In addition, Dr. Cohen is a former professor of psychiatry, family medicine, and otolaryngology at Thomas Jefferson University, Philadelphia. He has no conflicts of interest.

Ms. Cohen holds an MBA from Temple University, Philadelphia, with a focus on health care administration. Previously, Ms. Cohen was an associate administrator at Hahnemann University Hospital and an executive at the Health Services Council, both in Philadelphia. She currently writes biographical summaries of notable 18th- and 19th-century women. Ms. Cohen has no conflicts of interest.

During the ongoing COVID-19 pandemic, many people are spending endless hours at home looking at computer, phone, and television screens. Our population has turned to Internet use and television watching as a coping mechanism to deal with their isolation, boredom, stress, and fear of the virus. Indeed, some people have become addicted to watching television and binge-watching entire series in a single sitting on subscription streaming services.

A U.K. study showed that, during the lockdown, adults averaged spending 40% of their waking hours in front of a screen. After a long binge-watch, folks often forget what happened in the episodes or even the name of the program they viewed. When someone finds himself in this situation and can’t remember very much about what he actually watched, he feels as though he has wasted his own time and might become dysphoric and depressed. This type of viewer feels disconnected and forgets what he watched because he is experiencing passive enjoyment, rather than actively relating to the world.

So should television binge-watching give people feelings of guilt?

Fortunately, there are some positive factors about spending excessive time engrossed in these screens during a pandemic; some people use television viewing as a coping mechanism to deal with the reality and the fear of the coronavirus. Some beneficial aspects of television watching include:

• Escaping from the reality and stress of the pandemic in an emotionally safe, isolated cocoon.
• Experiencing safety from contracting COVID-19 by sheltering in place, isolating, and physical distancing from other people in the outside world.
• Experiencing a subdued, private, and mentally relaxing environment.
• Being productive and multitasking while watching television, for example, knit, sew, fold clothes, pay bills, write a letter, etc.

Despite many beneficial aspects of excessive television watching during the pandemic, we have to ask: Can too much television prove detrimental to our mental or physical well-being?
 

Associated mental, and physical problems

Cause and effect between excessive screen time and sleep disturbances is scientifically unproven, but there is an association between those factors.

Excessive screen time is associated with a sleep deficit, and a proper amount of sleep is necessary for optimal brain function, a healthy immune system, good memory, and overall well-being. Sleep cleans out the short-term memory stage from the information learned that day to make room for new memories. This allows us to store memories every day. An inadequate amount of sleep causes memory problems and cognitive deficits because we are not storing as many memories from days when we are sleep deprived. A good night’s sleep will prevent stress from one day to be carried over to the next day.

Lack of sleep affects people differently, but in some cases, a shortage of sleep can cause feelings of depression and isolation. Television, computer, and phone screens convey excessive damaging LED and blue light, detrimentally affecting our melatonin production and circadian rhythm. Blue light has wavelengths between 380 nm and 500 nm, and although blue wavelengths are beneficial in the day and increase positive mental mood, attention, and reaction times, blue wavelengths are destructive at night. Blue-light exposure suppresses the secretion of melatonin, which, as we know, is a hormone that influences circadian rhythms. The negative disruption of circadian rhythm throws the body’s biological clock in disarray and makes it more difficult for the mind to shut down at night.

Unfortunately, electronics with LED screens increase the amount of exposure to these blue wavelengths. In addition, the U.S. National Toxicology Program has suggested that a link exists between blue-light exposure at night to diabetes, heart disease, cancer, and obesity (Sci Tot Environ. 2017 Dec 31;[607-8]:1073-84).
 

Advice for patients and clinicians

Time spent watching television and using the Internet should be done in moderation. Make sure that patients understand that they should not feel guilty about watching television during these periods of isolation.

Encourage patients to be selective in their television viewing and to research available programs on streaming services and TV – and limit their screen time only to programs that truly interest them. Discourage them from watching television endlessly, hour after hour. Also, discourage patients from watching too much news. Instead, tell them to limit news to 1 hour per day, because news they perceive as bad might increase their overall anxiety.

Tell patients to engage in physical exercise every day; walk or run outside if possible. When inside, advise them to get up and walk around at least once per hour. Other advice we would like to offer patients and clinicians alike are:

• Put yourself on a schedule and go to sleep the same time each night and try to get 8 hours of sleep in a 24-hour period.
• Put away your devices 1 hour before going to bed or at least use dark mode, and wear blue-block glasses, since they are easier on the eyes and brain. Do not use television to put yourself to sleep. Spending too much time reading news stories is not a good idea, either, because doing so is mentally stimulating and can cause more uncertainty – making it difficult to sleep.
• Protect your eye health by purchasing and installing light bulbs with more internal red coating than blue. These bulbs will produce a warmer tone than the blue, and warmer tones will be less likely to shift circadian rhythm and suppress melatonin, thus reducing blue-light exposure. Blink your eyes often, and use eye solution for dry eyes.
• Sleep in total darkness to reduce your exposure to blue light. Take supplements with lutein and zeaxanthin, which may reduce the oxidative effects of blue light.

Encouraging patients to follow these guidelines – and adhering to them ourselves – should help us emerge from the COVID-19 pandemic mentally and physically healthy.

Dr. Cohen is board certified in psychiatry and has had a private practice in Philadelphia for more than 35 years. His areas of specialty include sports psychiatry, agoraphobia, depression, and substance abuse. In addition, Dr. Cohen is a former professor of psychiatry, family medicine, and otolaryngology at Thomas Jefferson University, Philadelphia. He has no conflicts of interest.

Ms. Cohen holds an MBA from Temple University, Philadelphia, with a focus on health care administration. Previously, Ms. Cohen was an associate administrator at Hahnemann University Hospital and an executive at the Health Services Council, both in Philadelphia. She currently writes biographical summaries of notable 18th- and 19th-century women. Ms. Cohen has no conflicts of interest.

During the ongoing COVID-19 pandemic, many people are spending endless hours at home looking at computer, phone, and television screens. Our population has turned to Internet use and television watching as a coping mechanism to deal with their isolation, boredom, stress, and fear of the virus. Indeed, some people have become addicted to watching television and binge-watching entire series in a single sitting on subscription streaming services.

A U.K. study showed that, during the lockdown, adults averaged spending 40% of their waking hours in front of a screen. After a long binge-watch, folks often forget what happened in the episodes or even the name of the program they viewed. When someone finds himself in this situation and can’t remember very much about what he actually watched, he feels as though he has wasted his own time and might become dysphoric and depressed. This type of viewer feels disconnected and forgets what he watched because he is experiencing passive enjoyment, rather than actively relating to the world.

So should television binge-watching give people feelings of guilt?

Fortunately, there are some positive factors about spending excessive time engrossed in these screens during a pandemic; some people use television viewing as a coping mechanism to deal with the reality and the fear of the coronavirus. Some beneficial aspects of television watching include:

• Escaping from the reality and stress of the pandemic in an emotionally safe, isolated cocoon.
• Experiencing safety from contracting COVID-19 by sheltering in place, isolating, and physical distancing from other people in the outside world.
• Experiencing a subdued, private, and mentally relaxing environment.
• Being productive and multitasking while watching television, for example, knit, sew, fold clothes, pay bills, write a letter, etc.

Despite many beneficial aspects of excessive television watching during the pandemic, we have to ask: Can too much television prove detrimental to our mental or physical well-being?
 

Associated mental, and physical problems

Cause and effect between excessive screen time and sleep disturbances is scientifically unproven, but there is an association between those factors.

Excessive screen time is associated with a sleep deficit, and a proper amount of sleep is necessary for optimal brain function, a healthy immune system, good memory, and overall well-being. Sleep cleans out the short-term memory stage from the information learned that day to make room for new memories. This allows us to store memories every day. An inadequate amount of sleep causes memory problems and cognitive deficits because we are not storing as many memories from days when we are sleep deprived. A good night’s sleep will prevent stress from one day to be carried over to the next day.

Lack of sleep affects people differently, but in some cases, a shortage of sleep can cause feelings of depression and isolation. Television, computer, and phone screens convey excessive damaging LED and blue light, detrimentally affecting our melatonin production and circadian rhythm. Blue light has wavelengths between 380 nm and 500 nm, and although blue wavelengths are beneficial in the day and increase positive mental mood, attention, and reaction times, blue wavelengths are destructive at night. Blue-light exposure suppresses the secretion of melatonin, which, as we know, is a hormone that influences circadian rhythms. The negative disruption of circadian rhythm throws the body’s biological clock in disarray and makes it more difficult for the mind to shut down at night.

Unfortunately, electronics with LED screens increase the amount of exposure to these blue wavelengths. In addition, the U.S. National Toxicology Program has suggested that a link exists between blue-light exposure at night to diabetes, heart disease, cancer, and obesity (Sci Tot Environ. 2017 Dec 31;[607-8]:1073-84).
 

Advice for patients and clinicians

Time spent watching television and using the Internet should be done in moderation. Make sure that patients understand that they should not feel guilty about watching television during these periods of isolation.

Encourage patients to be selective in their television viewing and to research available programs on streaming services and TV – and limit their screen time only to programs that truly interest them. Discourage them from watching television endlessly, hour after hour. Also, discourage patients from watching too much news. Instead, tell them to limit news to 1 hour per day, because news they perceive as bad might increase their overall anxiety.

Tell patients to engage in physical exercise every day; walk or run outside if possible. When inside, advise them to get up and walk around at least once per hour. Other advice we would like to offer patients and clinicians alike are:

• Put yourself on a schedule and go to sleep the same time each night and try to get 8 hours of sleep in a 24-hour period.
• Put away your devices 1 hour before going to bed or at least use dark mode, and wear blue-block glasses, since they are easier on the eyes and brain. Do not use television to put yourself to sleep. Spending too much time reading news stories is not a good idea, either, because doing so is mentally stimulating and can cause more uncertainty – making it difficult to sleep.
• Protect your eye health by purchasing and installing light bulbs with more internal red coating than blue. These bulbs will produce a warmer tone than the blue, and warmer tones will be less likely to shift circadian rhythm and suppress melatonin, thus reducing blue-light exposure. Blink your eyes often, and use eye solution for dry eyes.
• Sleep in total darkness to reduce your exposure to blue light. Take supplements with lutein and zeaxanthin, which may reduce the oxidative effects of blue light.

Encouraging patients to follow these guidelines – and adhering to them ourselves – should help us emerge from the COVID-19 pandemic mentally and physically healthy.

Dr. Cohen is board certified in psychiatry and has had a private practice in Philadelphia for more than 35 years. His areas of specialty include sports psychiatry, agoraphobia, depression, and substance abuse. In addition, Dr. Cohen is a former professor of psychiatry, family medicine, and otolaryngology at Thomas Jefferson University, Philadelphia. He has no conflicts of interest.

Ms. Cohen holds an MBA from Temple University, Philadelphia, with a focus on health care administration. Previously, Ms. Cohen was an associate administrator at Hahnemann University Hospital and an executive at the Health Services Council, both in Philadelphia. She currently writes biographical summaries of notable 18th- and 19th-century women. Ms. Cohen has no conflicts of interest.

In an ideal world, people could afford sacubitril/valsartan (Entresto), and clinicians would be allowed to prescribe it using clinical judgment as their guide. The imprimatur of an “[Food and Drug Administration]–labeled indication” would be unnecessary.

This is not our world. Guideline writers, third-party payers, and FDA regulators now play major roles in clinical decisions.

The angiotensin receptor neprilysin inhibitor is approved for use in patients with heart failure with reduced ejection fraction (HFrEF). In December 2020, an FDA advisory committee voted 12-1 in support of a vaguely worded question: Does PARAGON-HF provide sufficient evidence to support any indication for the drug in patients with heart failure with preserved ejection fraction (HFpEF)? The committee did not reach a consensus on what that indication should be.

Before I list five reasons why I hope the FDA does not approve the drug for any indication in patients with HFpEF, let’s review the seminal trial.
 

PARAGON-HF

PARAGON-HF randomly assigned slightly more than 4,800 patients with symptomatic HFpEF (left ventricular ejection fraction [LVEF] ≥45%) to sacubitril/valsartan or valsartan alone. The primary endpoint was total hospitalizations for heart failure (HHF) and death because of cardiovascular (CV) events.

Sacubitril/valsartan reduced the rate of the primary endpoint by 13% (rate ratio, 0.87; 95% confidence interval, 0.75-1.01; P = .06). There were 894 primary endpoint events in the sacubitril/valsartan arm, compared with 1,009 events in the valsartan arm.

The lower rate of events in the sacubitril/valsartan arm was driven by fewer hospitalizations for heart failure. CV death was essentially the same in both arms (204 deaths in the sacubitril/valsartan group versus 212 deaths in the valsartan group).

A note on the patients: the investigators screened more than 10,000 patients and enrolled less than half of them. The mean age was 73 years; 52% of patients were women, but only 2% were Black. The mean LVEF was 57%; 95% of patients had hypertension and were receiving diuretics at baseline.

Now to the five reasons not to approve the drug for this indication.
 

1. Uncertainty of benefit in HFpEF

A P value for the primary endpoint greater than the threshold of .05 suggests some degree of uncertainty. A nice way of describing this uncertainty is with a Bayesian analysis. Whereas a P value tells you the chance of seeing these results if the drug has no benefit, the Bayesian approach tells you the chance of drug benefit given the trial results.

By email, James Brophy, MD, a senior scientist in the Centre for Outcomes Research and Evaluation at McGill University, Montreal, showed me a Bayesian calculation of PARAGON-HF. He estimated a 38% chance that sacubitril/valsartan had a clinically meaningful 15% reduction in the primary endpoint, a 3% chance that it worsens outcomes, and a 58% chance that it is essentially no better than valsartan.

The take-home is that, in PARAGON-HF, a best-case scenario involving select high-risk patients with run-in periods and trial-level follow-up, there is substantial uncertainty as to whether the drug is any better than a generic standard.
 

2. Modest effect size in PARAGON-HF

Let’s assume the benefit seen in PARAGON-HF is not caused by chance. Was the effect clinically significant?

For context, consider the large effect size that sacubitril/valsartan had versus enalapril for patients with HFrEF.

In PARADIGM-HF, sacubitril/valsartan led to a 20% reduction in the composite primary endpoint. Importantly, this included equal reductions in both HHF and CV death. All-cause death was also significantly reduced in the active arm.

Because patients with HFpEF have a similarly poor prognosis as those with HFrEF, a truly beneficial drug should reduce not only HHF but also CV death and overall death. The lack of effect on these “harder” endpoints in PARAGON-HF points to a far more modest effect size for sacubitril/valsartan in HFpEF.

What’s more, even the signal of reduced HHF in PARAGON-HF is tenuous. The PARAGON-HF authors chose total HHF, whereas previous trials in patients with HFpEF used first HHF as their primary endpoint. Had PARAGON-HF followed the methods of prior trials, first HHF would not have made statistical significance (hazard ratio, 0.90; 95% CI, 0.79-1.04)
 

3. Subgroups not compelling

Proponents highlight the possibility that sacubitril/valsartan exerted a heterogenous effect in two subgroups.

In women, sacubitril/valsartan resulted in a 27% reduction in the primary endpoint (HR, 0.73; 95% CI, 0.59-0.90), whereas men showed no significant difference (HR, 1.03; 95% CI, 0.85-1.25). And the drug seemed to have little benefit over valsartan in patients with a median LVEF greater than 57%.

The problem with subgroups is that, if you look at enough of them, some can be positive on the basis of chance alone. For instance, patients enrolled in western Europe had an outsized benefit from sacubitril/valsartan, compared with patients from other areas.

FDA reviewers noted: “It is possible that the heterogeneity of treatment effect observed in the subgroups by gender and LVEF in PARAGON-HF is a chance finding.”

By email, clinical trial expert Sanjay Kaul, MD, from Cedars-Sinai Medical Center in Los Angeles, expressed serious concern with the subgroup analyses in PARAGON-HF because the sex interaction was confined to HHF alone. There was no interaction for other outcomes, such as CV death, all-cause mortality, renal endpoints, blood pressure, or lowering of N-terminal of the prohormone brain natriuretic peptide.

Similarly, the interaction with ejection fraction was confined to total HHF; it was not seen with New York Heart Association class improvement, all-cause mortality, quality of life, renal endpoints, or time to first event.

Dr. Kaul also emphasized something cardiologists know well, “that ejection fraction is not a static variable and is expected to change during the course of the trial.” This point makes it hard to believe that a partially subjective measurement, such as LVEF, could be a precise modifier of benefit.
 

4. Approval would stop research

If the FDA approves sacubitril/valsartan for patients with HFpEF, there is a near-zero chance we will learn whether there are subsets of patients who benefit more or less from the drug.

It will be the defibrillator problem all over again. Namely, while the average effect of a defibrillator is to reduce mortality in patients with HFrEF, in approximately 9 of 10 patients the implanted device is never used. Efforts to find subgroups that are most likely to need (or not need) an implantable defibrillator have been impossible because industry has no incentive to fund trials that may narrow the number of patients who qualify for their product.

It will be the same with sacubitril/valsartan. This is not nefarious; it is merely a limitation of industry funding of trials.
 

5. Opportunity costs

The category of HFpEF is vast.

FDA approval – even for a subset of these patients – would have huge cost implications. I understand cost issues are considered outside the purview of the FDA, but health care spending isn’t infinite. Money spent covering this costly drug is money not available for other things.

Despite this nation’s wealth, we struggle to provide even basic care to large numbers of people. Approval of an expensive drug with no or modest benefit will only exacerbate these stark disparities.
 

Conclusion

Given our current system of health care delivery, my pragmatic answer is for the FDA to say no to sacubitril/valsartan for HFpEF.

If you believe the drug has outsized benefits in women or those with mild impairment of systolic function, the way to answer these questions is not with subgroup analyses from a trial that did not reach statistical significance in its primary endpoint, but with more randomized trials. Isn’t that what “exploratory” subgroups are for?

Holding off on an indication for HFpEF will force proponents to define a subset of patients who garner a clear and substantial benefit from sacubitril/valsartan.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. MDedge is part of the Medscape Professional Network.

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

In an ideal world, people could afford sacubitril/valsartan (Entresto), and clinicians would be allowed to prescribe it using clinical judgment as their guide. The imprimatur of an “[Food and Drug Administration]–labeled indication” would be unnecessary.

This is not our world. Guideline writers, third-party payers, and FDA regulators now play major roles in clinical decisions.

The angiotensin receptor neprilysin inhibitor is approved for use in patients with heart failure with reduced ejection fraction (HFrEF). In December 2020, an FDA advisory committee voted 12-1 in support of a vaguely worded question: Does PARAGON-HF provide sufficient evidence to support any indication for the drug in patients with heart failure with preserved ejection fraction (HFpEF)? The committee did not reach a consensus on what that indication should be.

Before I list five reasons why I hope the FDA does not approve the drug for any indication in patients with HFpEF, let’s review the seminal trial.
 

PARAGON-HF

PARAGON-HF randomly assigned slightly more than 4,800 patients with symptomatic HFpEF (left ventricular ejection fraction [LVEF] ≥45%) to sacubitril/valsartan or valsartan alone. The primary endpoint was total hospitalizations for heart failure (HHF) and death because of cardiovascular (CV) events.

Sacubitril/valsartan reduced the rate of the primary endpoint by 13% (rate ratio, 0.87; 95% confidence interval, 0.75-1.01; P = .06). There were 894 primary endpoint events in the sacubitril/valsartan arm, compared with 1,009 events in the valsartan arm.

The lower rate of events in the sacubitril/valsartan arm was driven by fewer hospitalizations for heart failure. CV death was essentially the same in both arms (204 deaths in the sacubitril/valsartan group versus 212 deaths in the valsartan group).

A note on the patients: the investigators screened more than 10,000 patients and enrolled less than half of them. The mean age was 73 years; 52% of patients were women, but only 2% were Black. The mean LVEF was 57%; 95% of patients had hypertension and were receiving diuretics at baseline.

Now to the five reasons not to approve the drug for this indication.
 

1. Uncertainty of benefit in HFpEF

A P value for the primary endpoint greater than the threshold of .05 suggests some degree of uncertainty. A nice way of describing this uncertainty is with a Bayesian analysis. Whereas a P value tells you the chance of seeing these results if the drug has no benefit, the Bayesian approach tells you the chance of drug benefit given the trial results.

By email, James Brophy, MD, a senior scientist in the Centre for Outcomes Research and Evaluation at McGill University, Montreal, showed me a Bayesian calculation of PARAGON-HF. He estimated a 38% chance that sacubitril/valsartan had a clinically meaningful 15% reduction in the primary endpoint, a 3% chance that it worsens outcomes, and a 58% chance that it is essentially no better than valsartan.

The take-home is that, in PARAGON-HF, a best-case scenario involving select high-risk patients with run-in periods and trial-level follow-up, there is substantial uncertainty as to whether the drug is any better than a generic standard.
 

2. Modest effect size in PARAGON-HF

Let’s assume the benefit seen in PARAGON-HF is not caused by chance. Was the effect clinically significant?

For context, consider the large effect size that sacubitril/valsartan had versus enalapril for patients with HFrEF.

In PARADIGM-HF, sacubitril/valsartan led to a 20% reduction in the composite primary endpoint. Importantly, this included equal reductions in both HHF and CV death. All-cause death was also significantly reduced in the active arm.

Because patients with HFpEF have a similarly poor prognosis as those with HFrEF, a truly beneficial drug should reduce not only HHF but also CV death and overall death. The lack of effect on these “harder” endpoints in PARAGON-HF points to a far more modest effect size for sacubitril/valsartan in HFpEF.

What’s more, even the signal of reduced HHF in PARAGON-HF is tenuous. The PARAGON-HF authors chose total HHF, whereas previous trials in patients with HFpEF used first HHF as their primary endpoint. Had PARAGON-HF followed the methods of prior trials, first HHF would not have made statistical significance (hazard ratio, 0.90; 95% CI, 0.79-1.04)
 

3. Subgroups not compelling

Proponents highlight the possibility that sacubitril/valsartan exerted a heterogenous effect in two subgroups.

In women, sacubitril/valsartan resulted in a 27% reduction in the primary endpoint (HR, 0.73; 95% CI, 0.59-0.90), whereas men showed no significant difference (HR, 1.03; 95% CI, 0.85-1.25). And the drug seemed to have little benefit over valsartan in patients with a median LVEF greater than 57%.

The problem with subgroups is that, if you look at enough of them, some can be positive on the basis of chance alone. For instance, patients enrolled in western Europe had an outsized benefit from sacubitril/valsartan, compared with patients from other areas.

FDA reviewers noted: “It is possible that the heterogeneity of treatment effect observed in the subgroups by gender and LVEF in PARAGON-HF is a chance finding.”

By email, clinical trial expert Sanjay Kaul, MD, from Cedars-Sinai Medical Center in Los Angeles, expressed serious concern with the subgroup analyses in PARAGON-HF because the sex interaction was confined to HHF alone. There was no interaction for other outcomes, such as CV death, all-cause mortality, renal endpoints, blood pressure, or lowering of N-terminal of the prohormone brain natriuretic peptide.

Similarly, the interaction with ejection fraction was confined to total HHF; it was not seen with New York Heart Association class improvement, all-cause mortality, quality of life, renal endpoints, or time to first event.

Dr. Kaul also emphasized something cardiologists know well, “that ejection fraction is not a static variable and is expected to change during the course of the trial.” This point makes it hard to believe that a partially subjective measurement, such as LVEF, could be a precise modifier of benefit.
 

4. Approval would stop research

If the FDA approves sacubitril/valsartan for patients with HFpEF, there is a near-zero chance we will learn whether there are subsets of patients who benefit more or less from the drug.

It will be the defibrillator problem all over again. Namely, while the average effect of a defibrillator is to reduce mortality in patients with HFrEF, in approximately 9 of 10 patients the implanted device is never used. Efforts to find subgroups that are most likely to need (or not need) an implantable defibrillator have been impossible because industry has no incentive to fund trials that may narrow the number of patients who qualify for their product.

It will be the same with sacubitril/valsartan. This is not nefarious; it is merely a limitation of industry funding of trials.
 

5. Opportunity costs

The category of HFpEF is vast.

FDA approval – even for a subset of these patients – would have huge cost implications. I understand cost issues are considered outside the purview of the FDA, but health care spending isn’t infinite. Money spent covering this costly drug is money not available for other things.

Despite this nation’s wealth, we struggle to provide even basic care to large numbers of people. Approval of an expensive drug with no or modest benefit will only exacerbate these stark disparities.
 

Conclusion

Given our current system of health care delivery, my pragmatic answer is for the FDA to say no to sacubitril/valsartan for HFpEF.

If you believe the drug has outsized benefits in women or those with mild impairment of systolic function, the way to answer these questions is not with subgroup analyses from a trial that did not reach statistical significance in its primary endpoint, but with more randomized trials. Isn’t that what “exploratory” subgroups are for?

Holding off on an indication for HFpEF will force proponents to define a subset of patients who garner a clear and substantial benefit from sacubitril/valsartan.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. MDedge is part of the Medscape Professional Network.

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

In an ideal world, people could afford sacubitril/valsartan (Entresto), and clinicians would be allowed to prescribe it using clinical judgment as their guide. The imprimatur of an “[Food and Drug Administration]–labeled indication” would be unnecessary.

This is not our world. Guideline writers, third-party payers, and FDA regulators now play major roles in clinical decisions.

The angiotensin receptor neprilysin inhibitor is approved for use in patients with heart failure with reduced ejection fraction (HFrEF). In December 2020, an FDA advisory committee voted 12-1 in support of a vaguely worded question: Does PARAGON-HF provide sufficient evidence to support any indication for the drug in patients with heart failure with preserved ejection fraction (HFpEF)? The committee did not reach a consensus on what that indication should be.

Before I list five reasons why I hope the FDA does not approve the drug for any indication in patients with HFpEF, let’s review the seminal trial.
 

PARAGON-HF

PARAGON-HF randomly assigned slightly more than 4,800 patients with symptomatic HFpEF (left ventricular ejection fraction [LVEF] ≥45%) to sacubitril/valsartan or valsartan alone. The primary endpoint was total hospitalizations for heart failure (HHF) and death because of cardiovascular (CV) events.

Sacubitril/valsartan reduced the rate of the primary endpoint by 13% (rate ratio, 0.87; 95% confidence interval, 0.75-1.01; P = .06). There were 894 primary endpoint events in the sacubitril/valsartan arm, compared with 1,009 events in the valsartan arm.

The lower rate of events in the sacubitril/valsartan arm was driven by fewer hospitalizations for heart failure. CV death was essentially the same in both arms (204 deaths in the sacubitril/valsartan group versus 212 deaths in the valsartan group).

A note on the patients: the investigators screened more than 10,000 patients and enrolled less than half of them. The mean age was 73 years; 52% of patients were women, but only 2% were Black. The mean LVEF was 57%; 95% of patients had hypertension and were receiving diuretics at baseline.

Now to the five reasons not to approve the drug for this indication.
 

1. Uncertainty of benefit in HFpEF

A P value for the primary endpoint greater than the threshold of .05 suggests some degree of uncertainty. A nice way of describing this uncertainty is with a Bayesian analysis. Whereas a P value tells you the chance of seeing these results if the drug has no benefit, the Bayesian approach tells you the chance of drug benefit given the trial results.

By email, James Brophy, MD, a senior scientist in the Centre for Outcomes Research and Evaluation at McGill University, Montreal, showed me a Bayesian calculation of PARAGON-HF. He estimated a 38% chance that sacubitril/valsartan had a clinically meaningful 15% reduction in the primary endpoint, a 3% chance that it worsens outcomes, and a 58% chance that it is essentially no better than valsartan.

The take-home is that, in PARAGON-HF, a best-case scenario involving select high-risk patients with run-in periods and trial-level follow-up, there is substantial uncertainty as to whether the drug is any better than a generic standard.
 

2. Modest effect size in PARAGON-HF

Let’s assume the benefit seen in PARAGON-HF is not caused by chance. Was the effect clinically significant?

For context, consider the large effect size that sacubitril/valsartan had versus enalapril for patients with HFrEF.

In PARADIGM-HF, sacubitril/valsartan led to a 20% reduction in the composite primary endpoint. Importantly, this included equal reductions in both HHF and CV death. All-cause death was also significantly reduced in the active arm.

Because patients with HFpEF have a similarly poor prognosis as those with HFrEF, a truly beneficial drug should reduce not only HHF but also CV death and overall death. The lack of effect on these “harder” endpoints in PARAGON-HF points to a far more modest effect size for sacubitril/valsartan in HFpEF.

What’s more, even the signal of reduced HHF in PARAGON-HF is tenuous. The PARAGON-HF authors chose total HHF, whereas previous trials in patients with HFpEF used first HHF as their primary endpoint. Had PARAGON-HF followed the methods of prior trials, first HHF would not have made statistical significance (hazard ratio, 0.90; 95% CI, 0.79-1.04)
 

3. Subgroups not compelling

Proponents highlight the possibility that sacubitril/valsartan exerted a heterogenous effect in two subgroups.

In women, sacubitril/valsartan resulted in a 27% reduction in the primary endpoint (HR, 0.73; 95% CI, 0.59-0.90), whereas men showed no significant difference (HR, 1.03; 95% CI, 0.85-1.25). And the drug seemed to have little benefit over valsartan in patients with a median LVEF greater than 57%.

The problem with subgroups is that, if you look at enough of them, some can be positive on the basis of chance alone. For instance, patients enrolled in western Europe had an outsized benefit from sacubitril/valsartan, compared with patients from other areas.

FDA reviewers noted: “It is possible that the heterogeneity of treatment effect observed in the subgroups by gender and LVEF in PARAGON-HF is a chance finding.”

By email, clinical trial expert Sanjay Kaul, MD, from Cedars-Sinai Medical Center in Los Angeles, expressed serious concern with the subgroup analyses in PARAGON-HF because the sex interaction was confined to HHF alone. There was no interaction for other outcomes, such as CV death, all-cause mortality, renal endpoints, blood pressure, or lowering of N-terminal of the prohormone brain natriuretic peptide.

Similarly, the interaction with ejection fraction was confined to total HHF; it was not seen with New York Heart Association class improvement, all-cause mortality, quality of life, renal endpoints, or time to first event.

Dr. Kaul also emphasized something cardiologists know well, “that ejection fraction is not a static variable and is expected to change during the course of the trial.” This point makes it hard to believe that a partially subjective measurement, such as LVEF, could be a precise modifier of benefit.
 

4. Approval would stop research

If the FDA approves sacubitril/valsartan for patients with HFpEF, there is a near-zero chance we will learn whether there are subsets of patients who benefit more or less from the drug.

It will be the defibrillator problem all over again. Namely, while the average effect of a defibrillator is to reduce mortality in patients with HFrEF, in approximately 9 of 10 patients the implanted device is never used. Efforts to find subgroups that are most likely to need (or not need) an implantable defibrillator have been impossible because industry has no incentive to fund trials that may narrow the number of patients who qualify for their product.

It will be the same with sacubitril/valsartan. This is not nefarious; it is merely a limitation of industry funding of trials.
 

5. Opportunity costs

The category of HFpEF is vast.

FDA approval – even for a subset of these patients – would have huge cost implications. I understand cost issues are considered outside the purview of the FDA, but health care spending isn’t infinite. Money spent covering this costly drug is money not available for other things.

Despite this nation’s wealth, we struggle to provide even basic care to large numbers of people. Approval of an expensive drug with no or modest benefit will only exacerbate these stark disparities.
 

Conclusion

Given our current system of health care delivery, my pragmatic answer is for the FDA to say no to sacubitril/valsartan for HFpEF.

If you believe the drug has outsized benefits in women or those with mild impairment of systolic function, the way to answer these questions is not with subgroup analyses from a trial that did not reach statistical significance in its primary endpoint, but with more randomized trials. Isn’t that what “exploratory” subgroups are for?

Holding off on an indication for HFpEF will force proponents to define a subset of patients who garner a clear and substantial benefit from sacubitril/valsartan.

Dr. Mandrola practices cardiac electrophysiology in Louisville, Ky., and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. MDedge is part of the Medscape Professional Network.

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

While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.

Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m², solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.

Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.

As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.

I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:

Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
 

Does size reflect health?

Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.

A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.

Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
 

What about body positivity?

As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.

That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.

Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.

Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
 

Guiding the conversation

Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.

Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).

Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.

Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.

Arghavan Salles, MD, PhD, is a bariatric surgeon.

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

While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.

Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m², solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.

Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.

As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.

I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:

Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
 

Does size reflect health?

Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.

A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.

Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
 

What about body positivity?

As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.

That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.

Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.

Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
 

Guiding the conversation

Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.

Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).

Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.

Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.

Arghavan Salles, MD, PhD, is a bariatric surgeon.

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

While many people were committing to their New Year’s resolutions to lose weight, in January 2020 Cosmopolitan UK magazine released covers portraying 11 women of different shapes and sizes, with the headline, “This is healthy!” Each version of the cover features one or more of the 11 women wearing athletic gear and makeup, some of whom are caught mid-action – boxing, doing yoga, or simply rejoicing in being who they are. Seeing these, I was reminded of a patient I cared for as an intern.

Janet Spears (not her real name) was thin. Standing barely 5 feet 3 inches, she weighed 110 pounds. For those out there who think of size in terms of body mass index (BMI), it was about 20 kg/m², solidly in the “normal” category. At the age of 62, despite this healthy BMI, she had so much plaque in her arteries that she needed surgery to improve blood flow to her foot.

Admittedly, whenever I had read about people with high cholesterol, type 2 diabetes, or atherosclerosis, I pictured bigger people. But when I met Ms. Spears, I realized that one’s health cannot necessarily be inferred from physical appearance.

As a bariatric surgeon board certified in obesity medicine, I’ve probably spent more time thinking and learning about obesity than most people – and yet I still didn’t know what to make of the Cosmopolitan covers.

I saw the reaction on Twitter before I saw the magazines themselves, and I quickly observed a number of people decrying the covers, suggesting that they promote obesity:

Multiple people suggested that this was inappropriate, especially in the context of the COVID-19 pandemic and the fact that people with obesity are at risk for worse outcomes, compared with those without obesity. (As an aside, these comments suggest that people did not read the associated article, which is about fitness and body image more than it is about obesity.)
 

Does size reflect health?

Putting the pandemic aside for a moment, the question the magazine covers raise is whether physical appearance reflects health. That’s what got me thinking about Ms. Spears, who, though appearing healthy, was sick enough that she needed to have major surgery. This whole conversation hinges, of course, on one’s definition of health.

A common knee-jerk response, especially from physicians, would be to say that obesity is by definition unhealthy. Some researchers have suggested though that a segment of people with obesity fall into a category called metabolically healthy obesity, which is typically characterized by a limited set of data such as cholesterol, blood sugar, and blood pressure. Indeed, some people with obesity have normal values in those categories.

Being metabolically healthy, however, does not preclude other medical problems associated with obesity, including joint pain, cancer, and mood disorders, among other issues. So even those who have metabolically healthy obesity are not necessarily immune to the many other obesity-related conditions.
 

What about body positivity?

As I delved further into the conversation about these covers, I saw people embracing the idea of promoting different-sized bodies. With almost two thirds of the U.S. population having overweight or obesity, one might argue that it’s high time magazine covers and the media reflect the reality in our hometowns. Unrealistic images in the media are associated with negative self-image and disordered eating, so perhaps embracing the shapes of real people may help us all have healthier attitudes toward our bodies.

That said, this idea can be taken too far. The Health at Every Size movement, which some might consider to be the ultimate body-positivity movement, espouses the idea that size and health are completely unrelated. That crosses a line between what we know to be true – that, at a population level, higher weight is associated with more medical problems – and fake news.

Another idea to consider is fitness, as opposed to health. Fitness can be defined multiple ways, but if we consider it to be measured exercise capacity, those who are more fit have a longer life expectancy than those with lower fitness levels at a given BMI. While some feel that the Cosmopolitan covers promote obesity and are therefore irresponsible, it’s at least as likely that highlighting people with obesity being active may inspire others with obesity to do the same.

Now let’s bring the pandemic back into the picture. As much as we all wish that it was over, with uncontrolled spread in every state and record numbers of people dying, COVID-19 is still very much a part of our reality. Having obesity increases the risk of having a severe case of COVID-19 if infected. Patients with obesity are also more likely than those without obesity to be hospitalized, require intensive care, and die with COVID-19.
 

Guiding the conversation

Pandemic or not, the truth is that obesity is related to multiple medical problems. That does not mean that every person with obesity has medical problems. The musician Lizzo, for example, is someone with obesity who considers herself to be healthy. She posts images and videos of working out and shares her personal fitness routine with her millions of fans. As a physician, I worry about the medical conditions – metabolic or otherwise – that someone like her may develop. But I love how she embraces who she is while striving to be healthier.

Most of the critical comments I have seen about the Cosmopolitan covers have, at best, bordered on fat shaming; others are solidly in that category. And the vitriol aimed at the larger models is despicable. It seems that conversations about obesity often vacillate from one extreme (fat shaming) to the other (extreme body positivity).

Although it may not sell magazines, I would love to see more nuanced, fact-based discussions, both in the media and in our clinics. We can start by acknowledging the fact that people of different sizes can be healthy. The truth is that we can’t tell very much about a person’s health from their outward appearance, and we should probably stop trying to make such inferences.

Assessment of health is most accurately judged by each person with their medical team, not by observers who use media images as part of their own propaganda machine, pushing one extreme view or another. As physicians, we have the opportunity and the responsibility to support our patients in the pursuit of health, without shame or judgment. Maybe that’s a New Year’s resolution worth committing to.

Arghavan Salles, MD, PhD, is a bariatric surgeon.

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

Men have unique dermatologic needs yet are significantly less likely than women to visit a dermatologist’s office.¹ Male patients might have preconceived notions about the nature of dermatology visits and necessary areas of the body to be examined: For example, male patients might associate the genital examination with a urologist and not expect a dermatologist to complete such a seemingly private examination.²

Genital examinations are currently underperformed: Only one-quarter of dermatologists report examining a male patient’s genitals at most or all visits.³ In this commentary, we discuss the importance of genital examinations in men’s dermatology, specific issues that can arise, and strategies to enhance the quality and frequency of genital examinations in male patients.

Invaluable Aspect of Care

Thorough inspection of a male patient’s genital region is an important part of conducting a total-body skin examination (TBSE) for routine surveillance and evaluation of genital dermatoses. Sexually transmitted infections, warts, and other common lesions can be missed in diagnosis without careful inspection of the genital region. Additionally, scrotal malignancies, such as primary and metastatic melanoma and basal cell carcinoma, though rare, might be overlooked until symptoms become severe.^4,5

There is no substitute for a physical examination but, in certain circumstances, it might be appropriate for a dermatologist to ask a patient if he has concerning lesions on his genitals. However, patients often are unsure of worrisome signs, and areas of the perineum might not be easily visible to a patient. Genital inspection during the physical examination allows for a teachable moment, during which the dermatologist can educate the patient about benign lesions and variants, such as pearly penile papules, seborrheic keratoses, and sebaceous cysts.⁶ These lesions might not require intervention but should be monitored for atypical features or infection.⁶

Also, the dermatologist might incidentally discover transmissible lesions, such as condylomata caused by human papillomavirus, which has been shown to be present in approximately 50% of men in the United States⁷—many of whom are unaware. Inflammatory dermatoses, such as psoriasis, often affect the genitals and go unnoticed; prompt intervention can decrease the likelihood of complications.⁶

Protocol for Genital Examinations

To examine the genitals, all surfaces of the penis, scrotum, and perineum should be evaluated, with anatomic and pathologic variants noted. The patient or physician should stretch the penis, maneuvering it in multiple directions so that all aspects can be examined. In uncircumcised men, the foreskin should be retracted so that the head of the penis can be examined, followed by replacement of the foreskin by the patient.⁸ The scrotum also should be examined and lifted to fully view the perineum.

Providers should not grasp the penis with the whole hand but use the thumb and first finger to hold the head of the penis to maneuver it.⁸ Similarly, using the back of the hand and fingers to manipulate the genitals establishes boundaries and sets a clinical tone for the examination.

Unintentional Erection
Unique to the male dermatologic examination is the unintentional patient erection; a physician might be unsure of how to approach such a potentially awkward situation. An erection is not always an indication of sexual arousal; rather, it can reflect an autonomic reflex in response to physical stimulation. Erections occur commonly in health care settings, especially if the genitals are being manipulated.⁹

Generally, the course of action here depends on the patient’s response.¹⁰ For patients who appear unbothered, it might be appropriate to ignore the erection and proceed with the examination, especially if the physician is not actively examining the genital region. If the patient appears embarrassed, the physician can say “This is completely normal” or “Random erections are common” to normalize the situation. Joking or laughing should be avoided. For a patient who appears upset, the physician can step outside the room for a brief period to give the patient privacy, then re-enter and ask him if he is comfortable continuing with the examination.

When a patient develops an erection, the physician might become uncomfortable and, consciously or subconsciously, increase the pace of the examination, which is a natural tendency, but expediency at the expense of comprehensive care is inappropriate.

Examiner’s Body Language and Tone
Throughout the genital examination, the physician should be mindful of their comments and body language to avoid exacerbating patient vulnerability. Using anatomic terms, rather than colloquial ones, to describe the genitalia is advised to prevent misunderstanding and maintain a professional clinical environment. Providers should be prepared to explain anatomic terms because some patients are not familiar with medical terminology.

Presence of a Chaperone
Involving a chaperone, as recommended by the American Medical Association, might make a patient more comfortable and alleviate potential misunderstanding. Still, physicians should be aware that some patients might feel uncomfortable with a chaperone, interpreting their presence as an expectation of impropriety.¹¹ Universal offering of a chaperone to all patients, regardless of the gender of the physician, as well as appropriate signage in the clinical environment, normalizes chaperone invitation and use.

Other Helpful Considerations
Various strategies in the male genital examination can increase patient and physician comfort and improve care:

• The patient should be offered a gown before a TBSE or any skin examination during which the genitals will be examined.
• The patient should be allowed to keep his shorts or underwear on to avoid the feeling of being naked, which can provoke anxiety. Prior to beginning the examination, disclose that it will include “under the covered areas.”
• Ask the patient for permission to conduct the examination, enumerate the steps, and provide a rationale for a genital examination. These steps help gain cooperation, alleviate anticipation, and prevent surprise.
• To increase the patient’s comfort level, he can be asked whether he prefers to be examined supine or standing.
• Consider allowing the patient, himself, to expose and manipulate his genitals during the examination to increase his involvement and sense of autonomy.
• For genital examinations, patients often prefer that the examiner be a physician of the same gender. Accommodating a patient’s request regarding the examiner’s gender might not always be possible, but the medical practice should make an honest attempt to oblige.

Lastly, providers should be cognizant of the needs of male sexual and gender minority populations (ie, gay, bisexual, transgender/gender diverse, queer or questioning, intersex, and asexual persons). For example, transgender women might retain male anatomy or have surgical alteration of the genital region that also requires evaluation. In such patient populations, the genital examination is equally important to evaluate for dermatologic conditions that require treatment.

Final Thoughts

The male genital examination is an important component of the TBSE, as dermatologists can recognize lesions before symptoms present. Robust educational methods for trainees and practitioners in dermatology are lacking, and development of curricula might be beneficial to increase comfort in performing the genital examination. Still, use of the procedures described in this commentary can normalize the men’s genital examination, optimize the physical examination, and improve men’s overall dermatologic health.

Men have unique dermatologic needs yet are significantly less likely than women to visit a dermatologist’s office.¹ Male patients might have preconceived notions about the nature of dermatology visits and necessary areas of the body to be examined: For example, male patients might associate the genital examination with a urologist and not expect a dermatologist to complete such a seemingly private examination.²

Genital examinations are currently underperformed: Only one-quarter of dermatologists report examining a male patient’s genitals at most or all visits.³ In this commentary, we discuss the importance of genital examinations in men’s dermatology, specific issues that can arise, and strategies to enhance the quality and frequency of genital examinations in male patients.

Invaluable Aspect of Care

Thorough inspection of a male patient’s genital region is an important part of conducting a total-body skin examination (TBSE) for routine surveillance and evaluation of genital dermatoses. Sexually transmitted infections, warts, and other common lesions can be missed in diagnosis without careful inspection of the genital region. Additionally, scrotal malignancies, such as primary and metastatic melanoma and basal cell carcinoma, though rare, might be overlooked until symptoms become severe.^4,5

There is no substitute for a physical examination but, in certain circumstances, it might be appropriate for a dermatologist to ask a patient if he has concerning lesions on his genitals. However, patients often are unsure of worrisome signs, and areas of the perineum might not be easily visible to a patient. Genital inspection during the physical examination allows for a teachable moment, during which the dermatologist can educate the patient about benign lesions and variants, such as pearly penile papules, seborrheic keratoses, and sebaceous cysts.⁶ These lesions might not require intervention but should be monitored for atypical features or infection.⁶

Also, the dermatologist might incidentally discover transmissible lesions, such as condylomata caused by human papillomavirus, which has been shown to be present in approximately 50% of men in the United States⁷—many of whom are unaware. Inflammatory dermatoses, such as psoriasis, often affect the genitals and go unnoticed; prompt intervention can decrease the likelihood of complications.⁶

Protocol for Genital Examinations

To examine the genitals, all surfaces of the penis, scrotum, and perineum should be evaluated, with anatomic and pathologic variants noted. The patient or physician should stretch the penis, maneuvering it in multiple directions so that all aspects can be examined. In uncircumcised men, the foreskin should be retracted so that the head of the penis can be examined, followed by replacement of the foreskin by the patient.⁸ The scrotum also should be examined and lifted to fully view the perineum.

Providers should not grasp the penis with the whole hand but use the thumb and first finger to hold the head of the penis to maneuver it.⁸ Similarly, using the back of the hand and fingers to manipulate the genitals establishes boundaries and sets a clinical tone for the examination.

Unintentional Erection
Unique to the male dermatologic examination is the unintentional patient erection; a physician might be unsure of how to approach such a potentially awkward situation. An erection is not always an indication of sexual arousal; rather, it can reflect an autonomic reflex in response to physical stimulation. Erections occur commonly in health care settings, especially if the genitals are being manipulated.⁹

Generally, the course of action here depends on the patient’s response.¹⁰ For patients who appear unbothered, it might be appropriate to ignore the erection and proceed with the examination, especially if the physician is not actively examining the genital region. If the patient appears embarrassed, the physician can say “This is completely normal” or “Random erections are common” to normalize the situation. Joking or laughing should be avoided. For a patient who appears upset, the physician can step outside the room for a brief period to give the patient privacy, then re-enter and ask him if he is comfortable continuing with the examination.

When a patient develops an erection, the physician might become uncomfortable and, consciously or subconsciously, increase the pace of the examination, which is a natural tendency, but expediency at the expense of comprehensive care is inappropriate.

Examiner’s Body Language and Tone
Throughout the genital examination, the physician should be mindful of their comments and body language to avoid exacerbating patient vulnerability. Using anatomic terms, rather than colloquial ones, to describe the genitalia is advised to prevent misunderstanding and maintain a professional clinical environment. Providers should be prepared to explain anatomic terms because some patients are not familiar with medical terminology.

Presence of a Chaperone
Involving a chaperone, as recommended by the American Medical Association, might make a patient more comfortable and alleviate potential misunderstanding. Still, physicians should be aware that some patients might feel uncomfortable with a chaperone, interpreting their presence as an expectation of impropriety.¹¹ Universal offering of a chaperone to all patients, regardless of the gender of the physician, as well as appropriate signage in the clinical environment, normalizes chaperone invitation and use.

Other Helpful Considerations
Various strategies in the male genital examination can increase patient and physician comfort and improve care:

• The patient should be offered a gown before a TBSE or any skin examination during which the genitals will be examined.
• The patient should be allowed to keep his shorts or underwear on to avoid the feeling of being naked, which can provoke anxiety. Prior to beginning the examination, disclose that it will include “under the covered areas.”
• Ask the patient for permission to conduct the examination, enumerate the steps, and provide a rationale for a genital examination. These steps help gain cooperation, alleviate anticipation, and prevent surprise.
• To increase the patient’s comfort level, he can be asked whether he prefers to be examined supine or standing.
• Consider allowing the patient, himself, to expose and manipulate his genitals during the examination to increase his involvement and sense of autonomy.
• For genital examinations, patients often prefer that the examiner be a physician of the same gender. Accommodating a patient’s request regarding the examiner’s gender might not always be possible, but the medical practice should make an honest attempt to oblige.

Lastly, providers should be cognizant of the needs of male sexual and gender minority populations (ie, gay, bisexual, transgender/gender diverse, queer or questioning, intersex, and asexual persons). For example, transgender women might retain male anatomy or have surgical alteration of the genital region that also requires evaluation. In such patient populations, the genital examination is equally important to evaluate for dermatologic conditions that require treatment.

Final Thoughts

The male genital examination is an important component of the TBSE, as dermatologists can recognize lesions before symptoms present. Robust educational methods for trainees and practitioners in dermatology are lacking, and development of curricula might be beneficial to increase comfort in performing the genital examination. Still, use of the procedures described in this commentary can normalize the men’s genital examination, optimize the physical examination, and improve men’s overall dermatologic health.

Men have unique dermatologic needs yet are significantly less likely than women to visit a dermatologist’s office.¹ Male patients might have preconceived notions about the nature of dermatology visits and necessary areas of the body to be examined: For example, male patients might associate the genital examination with a urologist and not expect a dermatologist to complete such a seemingly private examination.²

Genital examinations are currently underperformed: Only one-quarter of dermatologists report examining a male patient’s genitals at most or all visits.³ In this commentary, we discuss the importance of genital examinations in men’s dermatology, specific issues that can arise, and strategies to enhance the quality and frequency of genital examinations in male patients.

Invaluable Aspect of Care

Thorough inspection of a male patient’s genital region is an important part of conducting a total-body skin examination (TBSE) for routine surveillance and evaluation of genital dermatoses. Sexually transmitted infections, warts, and other common lesions can be missed in diagnosis without careful inspection of the genital region. Additionally, scrotal malignancies, such as primary and metastatic melanoma and basal cell carcinoma, though rare, might be overlooked until symptoms become severe.^4,5

There is no substitute for a physical examination but, in certain circumstances, it might be appropriate for a dermatologist to ask a patient if he has concerning lesions on his genitals. However, patients often are unsure of worrisome signs, and areas of the perineum might not be easily visible to a patient. Genital inspection during the physical examination allows for a teachable moment, during which the dermatologist can educate the patient about benign lesions and variants, such as pearly penile papules, seborrheic keratoses, and sebaceous cysts.⁶ These lesions might not require intervention but should be monitored for atypical features or infection.⁶

Also, the dermatologist might incidentally discover transmissible lesions, such as condylomata caused by human papillomavirus, which has been shown to be present in approximately 50% of men in the United States⁷—many of whom are unaware. Inflammatory dermatoses, such as psoriasis, often affect the genitals and go unnoticed; prompt intervention can decrease the likelihood of complications.⁶

Protocol for Genital Examinations

To examine the genitals, all surfaces of the penis, scrotum, and perineum should be evaluated, with anatomic and pathologic variants noted. The patient or physician should stretch the penis, maneuvering it in multiple directions so that all aspects can be examined. In uncircumcised men, the foreskin should be retracted so that the head of the penis can be examined, followed by replacement of the foreskin by the patient.⁸ The scrotum also should be examined and lifted to fully view the perineum.

Providers should not grasp the penis with the whole hand but use the thumb and first finger to hold the head of the penis to maneuver it.⁸ Similarly, using the back of the hand and fingers to manipulate the genitals establishes boundaries and sets a clinical tone for the examination.

Unintentional Erection
Unique to the male dermatologic examination is the unintentional patient erection; a physician might be unsure of how to approach such a potentially awkward situation. An erection is not always an indication of sexual arousal; rather, it can reflect an autonomic reflex in response to physical stimulation. Erections occur commonly in health care settings, especially if the genitals are being manipulated.⁹

Generally, the course of action here depends on the patient’s response.¹⁰ For patients who appear unbothered, it might be appropriate to ignore the erection and proceed with the examination, especially if the physician is not actively examining the genital region. If the patient appears embarrassed, the physician can say “This is completely normal” or “Random erections are common” to normalize the situation. Joking or laughing should be avoided. For a patient who appears upset, the physician can step outside the room for a brief period to give the patient privacy, then re-enter and ask him if he is comfortable continuing with the examination.

When a patient develops an erection, the physician might become uncomfortable and, consciously or subconsciously, increase the pace of the examination, which is a natural tendency, but expediency at the expense of comprehensive care is inappropriate.

Examiner’s Body Language and Tone
Throughout the genital examination, the physician should be mindful of their comments and body language to avoid exacerbating patient vulnerability. Using anatomic terms, rather than colloquial ones, to describe the genitalia is advised to prevent misunderstanding and maintain a professional clinical environment. Providers should be prepared to explain anatomic terms because some patients are not familiar with medical terminology.

Presence of a Chaperone
Involving a chaperone, as recommended by the American Medical Association, might make a patient more comfortable and alleviate potential misunderstanding. Still, physicians should be aware that some patients might feel uncomfortable with a chaperone, interpreting their presence as an expectation of impropriety.¹¹ Universal offering of a chaperone to all patients, regardless of the gender of the physician, as well as appropriate signage in the clinical environment, normalizes chaperone invitation and use.

Other Helpful Considerations
Various strategies in the male genital examination can increase patient and physician comfort and improve care:

• The patient should be offered a gown before a TBSE or any skin examination during which the genitals will be examined.
• The patient should be allowed to keep his shorts or underwear on to avoid the feeling of being naked, which can provoke anxiety. Prior to beginning the examination, disclose that it will include “under the covered areas.”
• Ask the patient for permission to conduct the examination, enumerate the steps, and provide a rationale for a genital examination. These steps help gain cooperation, alleviate anticipation, and prevent surprise.
• To increase the patient’s comfort level, he can be asked whether he prefers to be examined supine or standing.
• Consider allowing the patient, himself, to expose and manipulate his genitals during the examination to increase his involvement and sense of autonomy.
• For genital examinations, patients often prefer that the examiner be a physician of the same gender. Accommodating a patient’s request regarding the examiner’s gender might not always be possible, but the medical practice should make an honest attempt to oblige.

Lastly, providers should be cognizant of the needs of male sexual and gender minority populations (ie, gay, bisexual, transgender/gender diverse, queer or questioning, intersex, and asexual persons). For example, transgender women might retain male anatomy or have surgical alteration of the genital region that also requires evaluation. In such patient populations, the genital examination is equally important to evaluate for dermatologic conditions that require treatment.

Final Thoughts

The male genital examination is an important component of the TBSE, as dermatologists can recognize lesions before symptoms present. Robust educational methods for trainees and practitioners in dermatology are lacking, and development of curricula might be beneficial to increase comfort in performing the genital examination. Still, use of the procedures described in this commentary can normalize the men’s genital examination, optimize the physical examination, and improve men’s overall dermatologic health.

Despite standard blood monitoring and routine imaging, patients with colorectal cancer (CRC) tend to have multiple, incurable metastases when relapse occurs.

A new study indicates that postsurgical circulating tumor DNA (ctDNA) testing may improve our ability to predict relapse in patients with stage I-III CRC.

ctDNA testing outperformed carcinoembryonic antigen (CEA) testing in predicting relapse-free survival, and ctDNA was detected about 8 months prior to relapse detection via CT.

Tenna V. Henriksen, of Aarhus University in Denmark, presented these results at the 2021 Gastrointestinal Cancers Symposium (abstract 11).

The multi-institutional study included 260 patients with CRC – 4 with stage I disease, 90 with stage II, and 166 with stage III disease.

Patients were monitored with plasma ctDNA testing within 2 months of primary surgery. Some patients were monitored with follow-up ctDNA sampling every 3 months for an additional 3 years.

Individual tumors and matched germline DNA were interrogated with whole-exome sequencing, and somatic single nucleotide variants were identified. Personalized multiplex PCR assays were developed to track tumor-specific single nucleotide variants via the Signatera® ctDNA assay.

The researchers retrospectively assessed ctDNA’s performance in:

• Stratifying the postoperative risk of relapse.
• Quantifying the benefit of adjuvant chemotherapy in patients who had or did not have ctDNA in plasma.
• Efficiently detecting relapse, in comparison with standard surveillance tests.

Surveillance CT scans were performed at 12 and 36 months but not at the frequency recommended in NCCN guidelines.

In all, 165 patients received adjuvant chemotherapy. The decision to give chemotherapy was made on a clinical basis by treating physicians who were blinded to the results of ctDNA testing.
 

Results

Of the 260 patients analyzed, 48 relapsed. The median follow-up was 28.4 months overall and 29.9 months in the nonrelapse cases.

The researchers assessed postoperative ctDNA status prior to adjuvant chemotherapy in 218 patients and after adjuvant chemotherapy in 108 patients.

In the prechemotherapy group, 20 patients were ctDNA positive, and 80% of them relapsed. In contrast, 13% of the 198 ctDNA-negative patients relapsed. The hazard ratio (HR) for relapse-free survival was 11 (95% confidence interval, 5.9-21; P < .0001).

After adjuvant chemotherapy, 12.5% of the ctDNA-negative patients relapsed, compared with 83.3% of the ctDNA-positive patients. The HR for relapse-free survival was 12 (95% CI, 4.9-27; P < .0001).

Results from longitudinal ctDNA testing in 202 patients suggested that serial sampling is more useful than sampling at a single point in time. The recurrence rate was 3.4% among patients who remained persistently ctDNA negative, compared with 89.3% in patients who were ctDNA positive. The HR for relapse-free survival was 51 (95% CI, 20-125; P < .0001).

In a subgroup of 29 patients with clinical recurrence detected by CT imaging, ctDNA detection occurred a median of 8.1 months earlier than radiologic relapse.

Among the 197 patients who had serial CEA and ctDNA measurements, longitudinal CEA testing correlated with relapse-free survival (HR, 4.9; 95% CI, 3.2-15, P < .0001) but not nearly as well as ctDNA testing (HR, 95.7; 95% CI, 28-322, P < .0001) in a univariable analysis.

In a multivariable analysis, the HR for relapse-free survival was 1.8 (95% CI, 0.77-4.0; P = .184) for longitudinal CEA and 80.55 (95% CI, 23.1-281; P < .0001) for longitudinal ctDNA.

“[W]hen we pit them against each other in a multivariable analysis, we can see that all the predictive power is in the ctDNA samples,” Ms. Henriksen said. “This indicates that ctDNA is a stronger biomarker compared to CEA, at least with relapse-free survival.”

Availability is not actionability

Study discussant Michael J. Overman, MD, of MD Anderson Cancer Center in Houston, acknowledged that this research substantiates the ability of postoperative ctDNA detection to risk stratify patients with stage III CRC, the predominant stage of participants in the study.

The current results reinforce the researchers’ previously published work (JAMA Oncol. 2019;5[8]:1124-31) and affirm similar findings by other groups (JAMA Oncol. 2019;5[12]:1710-17 and JAMA Oncol. 2019;5[8]:1118-23).

However, Dr. Overman cautioned that “availability is not the same as actionability.”

He also said the “tumor-informed mutation” approach utilized in the Signatera assay differs from the simpler “panel-based” approach, which is also undergoing clinical testing and offers the additional opportunity to test potentially actionable epigenetic targets such as DNA methylation.

Furthermore, the practicality of integrating the tumor-informed mutation approach into the time constraints required in clinical practice was not evaluated in the current analysis.

Dr. Overman pointed out that 16 of the 20 ctDNA-positive patients who received adjuvant chemotherapy sustained a recurrence, so the chemotherapy benefit was lower than expected.

Finally, although ctDNA outperformed CEA in detecting relapse, the greatest impact of ctDNA is its potential to inform the clinician’s decision to escalate and deescalate treatment with impact on survival – a potential that remains unfulfilled.

Next steps

Ms. Henriksen closed her presentation with the perspective that, for serial ctDNA monitoring to be implemented in clinical settings, testing in randomized clinical trials will be needed.

In Denmark, the IMPROVE-IT study is enrolling patients with stage I or low-risk stage II CRC. In this trial, ctDNA-positive patients will receive adjuvant chemotherapy, and ctDNA-negative patients will have longitudinal ctDNA testing but no adjuvant chemotherapy.

A second study, IMPROVE-IT2, will assess the value of ctDNA to direct intensified radiologic surveillance to improve the application of potentially curative treatment for patients with stage II (high-risk) or stage III CRC. Patients with negative ctDNA tests will be followed with longitudinal ctDNA testing only.

In his talk, Dr. Overman highlighted several prospective studies assessing the value of ctDNA testing.

One of these is the ongoing COBRA study (NRG-GI-005), which uses a ctDNA assay (Guardant Lunar-1) for patients with stage IIA CRC for whom standard adjuvant chemotherapy is not indicated.

The patients in COBRA are randomized to active surveillance or assay-directed therapy. Patients assigned to assay-directed therapy have samples analyzed for ctDNA, which would guide the decision about adjuvant chemotherapy. If the postoperative sample is ctDNA positive and the patient accepts adjuvant chemotherapy, the patient could receive one of two standard adjuvant chemotherapy regimens. If ctDNA negative, the patient would be followed with active surveillance alone.

Dr. Overman also highlighted the planned CIRCULATE US trial (NRG-GI008). The aim of this trial is to test intensified adjuvant treatment for stage III CRC patients with positive ctDNA tests. It will employ the Signatera assay.

Ideally, these ongoing trials will provide the evidence base needed for clinicians to optimize adjuvant therapy and surveillance using ctDNA technology.

The current study was sponsored by the Danish Council for Independent Research, The Novo Nordisk Foundation, The Danish Cancer Society, and Natera Inc. Ms. Henriksen disclosed no conflicts of interest. Dr. Overman disclosed relationships with Array BioPharma, Bristol-Myers Squibb, Gritstone Oncology, Janssen, MedImmune, Merck, Novartis, Pfizer, Promega, Roche/Genentech, and Spectrum Pharmaceuticals.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
 

Despite standard blood monitoring and routine imaging, patients with colorectal cancer (CRC) tend to have multiple, incurable metastases when relapse occurs.

A new study indicates that postsurgical circulating tumor DNA (ctDNA) testing may improve our ability to predict relapse in patients with stage I-III CRC.

ctDNA testing outperformed carcinoembryonic antigen (CEA) testing in predicting relapse-free survival, and ctDNA was detected about 8 months prior to relapse detection via CT.

Tenna V. Henriksen, of Aarhus University in Denmark, presented these results at the 2021 Gastrointestinal Cancers Symposium (abstract 11).

The multi-institutional study included 260 patients with CRC – 4 with stage I disease, 90 with stage II, and 166 with stage III disease.

Patients were monitored with plasma ctDNA testing within 2 months of primary surgery. Some patients were monitored with follow-up ctDNA sampling every 3 months for an additional 3 years.

Individual tumors and matched germline DNA were interrogated with whole-exome sequencing, and somatic single nucleotide variants were identified. Personalized multiplex PCR assays were developed to track tumor-specific single nucleotide variants via the Signatera® ctDNA assay.

The researchers retrospectively assessed ctDNA’s performance in:

• Stratifying the postoperative risk of relapse.
• Quantifying the benefit of adjuvant chemotherapy in patients who had or did not have ctDNA in plasma.
• Efficiently detecting relapse, in comparison with standard surveillance tests.

Surveillance CT scans were performed at 12 and 36 months but not at the frequency recommended in NCCN guidelines.

In all, 165 patients received adjuvant chemotherapy. The decision to give chemotherapy was made on a clinical basis by treating physicians who were blinded to the results of ctDNA testing.
 

Results

Of the 260 patients analyzed, 48 relapsed. The median follow-up was 28.4 months overall and 29.9 months in the nonrelapse cases.

The researchers assessed postoperative ctDNA status prior to adjuvant chemotherapy in 218 patients and after adjuvant chemotherapy in 108 patients.

In the prechemotherapy group, 20 patients were ctDNA positive, and 80% of them relapsed. In contrast, 13% of the 198 ctDNA-negative patients relapsed. The hazard ratio (HR) for relapse-free survival was 11 (95% confidence interval, 5.9-21; P < .0001).

After adjuvant chemotherapy, 12.5% of the ctDNA-negative patients relapsed, compared with 83.3% of the ctDNA-positive patients. The HR for relapse-free survival was 12 (95% CI, 4.9-27; P < .0001).

Results from longitudinal ctDNA testing in 202 patients suggested that serial sampling is more useful than sampling at a single point in time. The recurrence rate was 3.4% among patients who remained persistently ctDNA negative, compared with 89.3% in patients who were ctDNA positive. The HR for relapse-free survival was 51 (95% CI, 20-125; P < .0001).

In a subgroup of 29 patients with clinical recurrence detected by CT imaging, ctDNA detection occurred a median of 8.1 months earlier than radiologic relapse.

Among the 197 patients who had serial CEA and ctDNA measurements, longitudinal CEA testing correlated with relapse-free survival (HR, 4.9; 95% CI, 3.2-15, P < .0001) but not nearly as well as ctDNA testing (HR, 95.7; 95% CI, 28-322, P < .0001) in a univariable analysis.

In a multivariable analysis, the HR for relapse-free survival was 1.8 (95% CI, 0.77-4.0; P = .184) for longitudinal CEA and 80.55 (95% CI, 23.1-281; P < .0001) for longitudinal ctDNA.

“[W]hen we pit them against each other in a multivariable analysis, we can see that all the predictive power is in the ctDNA samples,” Ms. Henriksen said. “This indicates that ctDNA is a stronger biomarker compared to CEA, at least with relapse-free survival.”

Availability is not actionability

Study discussant Michael J. Overman, MD, of MD Anderson Cancer Center in Houston, acknowledged that this research substantiates the ability of postoperative ctDNA detection to risk stratify patients with stage III CRC, the predominant stage of participants in the study.

The current results reinforce the researchers’ previously published work (JAMA Oncol. 2019;5[8]:1124-31) and affirm similar findings by other groups (JAMA Oncol. 2019;5[12]:1710-17 and JAMA Oncol. 2019;5[8]:1118-23).

However, Dr. Overman cautioned that “availability is not the same as actionability.”

He also said the “tumor-informed mutation” approach utilized in the Signatera assay differs from the simpler “panel-based” approach, which is also undergoing clinical testing and offers the additional opportunity to test potentially actionable epigenetic targets such as DNA methylation.

Furthermore, the practicality of integrating the tumor-informed mutation approach into the time constraints required in clinical practice was not evaluated in the current analysis.

Dr. Overman pointed out that 16 of the 20 ctDNA-positive patients who received adjuvant chemotherapy sustained a recurrence, so the chemotherapy benefit was lower than expected.

Finally, although ctDNA outperformed CEA in detecting relapse, the greatest impact of ctDNA is its potential to inform the clinician’s decision to escalate and deescalate treatment with impact on survival – a potential that remains unfulfilled.

Next steps

Ms. Henriksen closed her presentation with the perspective that, for serial ctDNA monitoring to be implemented in clinical settings, testing in randomized clinical trials will be needed.

In Denmark, the IMPROVE-IT study is enrolling patients with stage I or low-risk stage II CRC. In this trial, ctDNA-positive patients will receive adjuvant chemotherapy, and ctDNA-negative patients will have longitudinal ctDNA testing but no adjuvant chemotherapy.

A second study, IMPROVE-IT2, will assess the value of ctDNA to direct intensified radiologic surveillance to improve the application of potentially curative treatment for patients with stage II (high-risk) or stage III CRC. Patients with negative ctDNA tests will be followed with longitudinal ctDNA testing only.

In his talk, Dr. Overman highlighted several prospective studies assessing the value of ctDNA testing.

One of these is the ongoing COBRA study (NRG-GI-005), which uses a ctDNA assay (Guardant Lunar-1) for patients with stage IIA CRC for whom standard adjuvant chemotherapy is not indicated.

The patients in COBRA are randomized to active surveillance or assay-directed therapy. Patients assigned to assay-directed therapy have samples analyzed for ctDNA, which would guide the decision about adjuvant chemotherapy. If the postoperative sample is ctDNA positive and the patient accepts adjuvant chemotherapy, the patient could receive one of two standard adjuvant chemotherapy regimens. If ctDNA negative, the patient would be followed with active surveillance alone.

Dr. Overman also highlighted the planned CIRCULATE US trial (NRG-GI008). The aim of this trial is to test intensified adjuvant treatment for stage III CRC patients with positive ctDNA tests. It will employ the Signatera assay.

Ideally, these ongoing trials will provide the evidence base needed for clinicians to optimize adjuvant therapy and surveillance using ctDNA technology.

The current study was sponsored by the Danish Council for Independent Research, The Novo Nordisk Foundation, The Danish Cancer Society, and Natera Inc. Ms. Henriksen disclosed no conflicts of interest. Dr. Overman disclosed relationships with Array BioPharma, Bristol-Myers Squibb, Gritstone Oncology, Janssen, MedImmune, Merck, Novartis, Pfizer, Promega, Roche/Genentech, and Spectrum Pharmaceuticals.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
 

Despite standard blood monitoring and routine imaging, patients with colorectal cancer (CRC) tend to have multiple, incurable metastases when relapse occurs.

A new study indicates that postsurgical circulating tumor DNA (ctDNA) testing may improve our ability to predict relapse in patients with stage I-III CRC.

ctDNA testing outperformed carcinoembryonic antigen (CEA) testing in predicting relapse-free survival, and ctDNA was detected about 8 months prior to relapse detection via CT.

Tenna V. Henriksen, of Aarhus University in Denmark, presented these results at the 2021 Gastrointestinal Cancers Symposium (abstract 11).

The multi-institutional study included 260 patients with CRC – 4 with stage I disease, 90 with stage II, and 166 with stage III disease.

Patients were monitored with plasma ctDNA testing within 2 months of primary surgery. Some patients were monitored with follow-up ctDNA sampling every 3 months for an additional 3 years.

Individual tumors and matched germline DNA were interrogated with whole-exome sequencing, and somatic single nucleotide variants were identified. Personalized multiplex PCR assays were developed to track tumor-specific single nucleotide variants via the Signatera® ctDNA assay.

The researchers retrospectively assessed ctDNA’s performance in:

• Stratifying the postoperative risk of relapse.
• Quantifying the benefit of adjuvant chemotherapy in patients who had or did not have ctDNA in plasma.
• Efficiently detecting relapse, in comparison with standard surveillance tests.

Surveillance CT scans were performed at 12 and 36 months but not at the frequency recommended in NCCN guidelines.

In all, 165 patients received adjuvant chemotherapy. The decision to give chemotherapy was made on a clinical basis by treating physicians who were blinded to the results of ctDNA testing.
 

Results

Of the 260 patients analyzed, 48 relapsed. The median follow-up was 28.4 months overall and 29.9 months in the nonrelapse cases.

The researchers assessed postoperative ctDNA status prior to adjuvant chemotherapy in 218 patients and after adjuvant chemotherapy in 108 patients.

In the prechemotherapy group, 20 patients were ctDNA positive, and 80% of them relapsed. In contrast, 13% of the 198 ctDNA-negative patients relapsed. The hazard ratio (HR) for relapse-free survival was 11 (95% confidence interval, 5.9-21; P < .0001).

After adjuvant chemotherapy, 12.5% of the ctDNA-negative patients relapsed, compared with 83.3% of the ctDNA-positive patients. The HR for relapse-free survival was 12 (95% CI, 4.9-27; P < .0001).

Results from longitudinal ctDNA testing in 202 patients suggested that serial sampling is more useful than sampling at a single point in time. The recurrence rate was 3.4% among patients who remained persistently ctDNA negative, compared with 89.3% in patients who were ctDNA positive. The HR for relapse-free survival was 51 (95% CI, 20-125; P < .0001).

In a subgroup of 29 patients with clinical recurrence detected by CT imaging, ctDNA detection occurred a median of 8.1 months earlier than radiologic relapse.

Among the 197 patients who had serial CEA and ctDNA measurements, longitudinal CEA testing correlated with relapse-free survival (HR, 4.9; 95% CI, 3.2-15, P < .0001) but not nearly as well as ctDNA testing (HR, 95.7; 95% CI, 28-322, P < .0001) in a univariable analysis.

In a multivariable analysis, the HR for relapse-free survival was 1.8 (95% CI, 0.77-4.0; P = .184) for longitudinal CEA and 80.55 (95% CI, 23.1-281; P < .0001) for longitudinal ctDNA.

“[W]hen we pit them against each other in a multivariable analysis, we can see that all the predictive power is in the ctDNA samples,” Ms. Henriksen said. “This indicates that ctDNA is a stronger biomarker compared to CEA, at least with relapse-free survival.”

Availability is not actionability

Study discussant Michael J. Overman, MD, of MD Anderson Cancer Center in Houston, acknowledged that this research substantiates the ability of postoperative ctDNA detection to risk stratify patients with stage III CRC, the predominant stage of participants in the study.

The current results reinforce the researchers’ previously published work (JAMA Oncol. 2019;5[8]:1124-31) and affirm similar findings by other groups (JAMA Oncol. 2019;5[12]:1710-17 and JAMA Oncol. 2019;5[8]:1118-23).

However, Dr. Overman cautioned that “availability is not the same as actionability.”

He also said the “tumor-informed mutation” approach utilized in the Signatera assay differs from the simpler “panel-based” approach, which is also undergoing clinical testing and offers the additional opportunity to test potentially actionable epigenetic targets such as DNA methylation.

Furthermore, the practicality of integrating the tumor-informed mutation approach into the time constraints required in clinical practice was not evaluated in the current analysis.

Dr. Overman pointed out that 16 of the 20 ctDNA-positive patients who received adjuvant chemotherapy sustained a recurrence, so the chemotherapy benefit was lower than expected.

Finally, although ctDNA outperformed CEA in detecting relapse, the greatest impact of ctDNA is its potential to inform the clinician’s decision to escalate and deescalate treatment with impact on survival – a potential that remains unfulfilled.

Next steps

Ms. Henriksen closed her presentation with the perspective that, for serial ctDNA monitoring to be implemented in clinical settings, testing in randomized clinical trials will be needed.

In Denmark, the IMPROVE-IT study is enrolling patients with stage I or low-risk stage II CRC. In this trial, ctDNA-positive patients will receive adjuvant chemotherapy, and ctDNA-negative patients will have longitudinal ctDNA testing but no adjuvant chemotherapy.

A second study, IMPROVE-IT2, will assess the value of ctDNA to direct intensified radiologic surveillance to improve the application of potentially curative treatment for patients with stage II (high-risk) or stage III CRC. Patients with negative ctDNA tests will be followed with longitudinal ctDNA testing only.

In his talk, Dr. Overman highlighted several prospective studies assessing the value of ctDNA testing.

One of these is the ongoing COBRA study (NRG-GI-005), which uses a ctDNA assay (Guardant Lunar-1) for patients with stage IIA CRC for whom standard adjuvant chemotherapy is not indicated.

The patients in COBRA are randomized to active surveillance or assay-directed therapy. Patients assigned to assay-directed therapy have samples analyzed for ctDNA, which would guide the decision about adjuvant chemotherapy. If the postoperative sample is ctDNA positive and the patient accepts adjuvant chemotherapy, the patient could receive one of two standard adjuvant chemotherapy regimens. If ctDNA negative, the patient would be followed with active surveillance alone.

Dr. Overman also highlighted the planned CIRCULATE US trial (NRG-GI008). The aim of this trial is to test intensified adjuvant treatment for stage III CRC patients with positive ctDNA tests. It will employ the Signatera assay.

Ideally, these ongoing trials will provide the evidence base needed for clinicians to optimize adjuvant therapy and surveillance using ctDNA technology.

The current study was sponsored by the Danish Council for Independent Research, The Novo Nordisk Foundation, The Danish Cancer Society, and Natera Inc. Ms. Henriksen disclosed no conflicts of interest. Dr. Overman disclosed relationships with Array BioPharma, Bristol-Myers Squibb, Gritstone Oncology, Janssen, MedImmune, Merck, Novartis, Pfizer, Promega, Roche/Genentech, and Spectrum Pharmaceuticals.

The Gastrointestinal Cancers Symposium is sponsored by the American Gastroenterological Association, the American Society for Clinical Oncology, the American Society for Radiation Oncology, and the Society of Surgical Oncology.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
 

A 61-year-old man is seen for a primary care visit. He has a history of colonic polyps (tubular adenoma) on two previous colonoscopies (at age 50 and 55). He has been on an appropriate 5-year schedule, but is overdue for his colonoscopy. He did not follow up with messages from his gastroenterologist for scheduling his colonoscopy last year. He explains he really hates the whole preparation for colonoscopy, but does realize he needs to follow up, and is willing to do so now. What do you recommend for colonoscopy prep?

A) Diet as usual until 5 p.m. day before, then clear liquid diet. Start GoLYTELY (1 gallon) night before procedure.

B) Low-fiber diet X2 days, clear liquid diet day before procedure, GoLYTELY (1 gallon) night before procedure.

C) Low residue diet X3 days, SUPREP the night before the procedure.

D) Low residue diet X2 days, followed by clear liquid diet the day before the procedure, SUPREP the night before the procedure.
 

It is common for patients to be reluctant to follow recommendations for colonoscopy due to dreading the prep. I would recommend choice C here, as the least difficult bowel preparation for colonoscopy.

Gastroenterologists are usually the ones to recommend the bowel prep that they want their patients to follow. When patients avoid needed colonoscopies because they hate the prep they are advised to take, I think it is good for primary care professionals to step in and discuss evidence-based alternatives.

Major diet change for several days before colonoscopy is difficult for many patients. Standard advice is that patients eat only low-fiber foods starting 3 days before the procedure. Patients are advised to switch to a completely clear liquid diet 1-2 days before the colonoscopy.

Are there more tolerable diets to offer patients?

Soweid and colleagues randomized 200 patients to a low residue diet for the three meals the day before colonoscopy vs. clear liquid diet.¹ The low residue diet allowed patients to eat meat, eggs, cheese, bread, rice, and ice cream. Not surprisingly, patients tolerated the low residue diet better with statistically significantly less nausea, vomiting, weakness, headache, sleep difficulties, and hunger. The patients in the low residue diet group also had better bowel prep than did those in the clear liquid diet group (81% vs. 52%, P less than 0.001).¹

In a recent meta- analysis, low residue diets were comparable to clear liquid diets in regard to adequacy of bowel prep and for detection of polyps.² Patients who followed low residue diets had statistically significantly less headaches, nausea, vomiting, and hunger. Very importantly, patients who followed low residue diets showed an increased willingness to repeat it, compared with those who followed a clear liquid diet (P less than .005; odds ratio, 2.23; 95% confidence interval, 1.28-3.89).²

What alternatives to GoLYTELY exist?

Another part of the bowel prep that patients struggle with is drinking a gallon of GoLYTELY (polyethylene glycol/electrolytes). Drinking that amount of this nasty stuff is never welcome.

There are a number of lower-volume alternatives that are as effective as GoLYTELY. Sarvepalli and colleagues did a retrospective study of 75,874 patients who had a colonoscopy in the Cleveland Clinic health system.³ The choice of bowel prep was not associated with adenoma detection.

Patients who lower volume preparations (2 quarts) SUPREP, MoviPrep, Osmoprep and HalfLytely had varying results of rates of inadequate bowel prep compared with patients who took GoLYTELY. Results for patients taking SUPREP and MoviPrep were statistically significantly better than for patients taking GoLYTELY. Results for patients taking OsmoPrep were not statistically different from those for patients taking GoLYTELY. Rates of inadequate bowel prep were statistically higher, meaning worse, for patients taking HalfLytely vs. patients taking GoLYTELY.³

Gu and colleagues did a prospective study of bowel prep outcomes from 4,339 colonoscopies, involving 75 different endoscopists.⁴ There was a wide range of bowel preps used, including low- and high-volume bowel preps. The low-volume preparations, SUPREP (P less than .001), MoviPrep (P less than .004) and MiraLAX with Gatorade (P less than .001), were superior to GoLYTELY for bowel cleansing. This was based on scoring via the Boston Bowel Preparation Scale. All were better tolerated than GoLYTELY.



Myth: All patients need a clear liquid diet and GoLYTELY for their bowel prep.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Soweid AM et al. A randomized single-blind trial of standard diet versus fiber-free diet with polyethylene glycol electrolyte solution for colonoscopy preparation. Endoscopy 2010;42:633-8.

2. Zhang X et al. Low-[residue] diet versus clear-liquid diet for bowel preparation before colonoscopy: meta-analysis and trial sequential analysis of randomized controlled trials. Gastrointest Endosc. 2020 Sep;92(3):508-18.

3. Sarvepalli S et al. Comparative effectiveness of commercial bowel preparations in ambulatory patients presenting for screening or surveillance colonoscopy. Dig Dis Sci. 2020 Jul 20. doi: 10.1007/s10620-020-06492-z.

4. Gu P et al. Comparing the real-world effectiveness of competing colonoscopy preparations: results of a prospective trial. Am J Gastroenterol. 2019;114(2):305-14.

A 61-year-old man is seen for a primary care visit. He has a history of colonic polyps (tubular adenoma) on two previous colonoscopies (at age 50 and 55). He has been on an appropriate 5-year schedule, but is overdue for his colonoscopy. He did not follow up with messages from his gastroenterologist for scheduling his colonoscopy last year. He explains he really hates the whole preparation for colonoscopy, but does realize he needs to follow up, and is willing to do so now. What do you recommend for colonoscopy prep?

A) Diet as usual until 5 p.m. day before, then clear liquid diet. Start GoLYTELY (1 gallon) night before procedure.

B) Low-fiber diet X2 days, clear liquid diet day before procedure, GoLYTELY (1 gallon) night before procedure.

C) Low residue diet X3 days, SUPREP the night before the procedure.

D) Low residue diet X2 days, followed by clear liquid diet the day before the procedure, SUPREP the night before the procedure.
 

It is common for patients to be reluctant to follow recommendations for colonoscopy due to dreading the prep. I would recommend choice C here, as the least difficult bowel preparation for colonoscopy.

Gastroenterologists are usually the ones to recommend the bowel prep that they want their patients to follow. When patients avoid needed colonoscopies because they hate the prep they are advised to take, I think it is good for primary care professionals to step in and discuss evidence-based alternatives.

Major diet change for several days before colonoscopy is difficult for many patients. Standard advice is that patients eat only low-fiber foods starting 3 days before the procedure. Patients are advised to switch to a completely clear liquid diet 1-2 days before the colonoscopy.

Are there more tolerable diets to offer patients?

Soweid and colleagues randomized 200 patients to a low residue diet for the three meals the day before colonoscopy vs. clear liquid diet.¹ The low residue diet allowed patients to eat meat, eggs, cheese, bread, rice, and ice cream. Not surprisingly, patients tolerated the low residue diet better with statistically significantly less nausea, vomiting, weakness, headache, sleep difficulties, and hunger. The patients in the low residue diet group also had better bowel prep than did those in the clear liquid diet group (81% vs. 52%, P less than 0.001).¹

In a recent meta- analysis, low residue diets were comparable to clear liquid diets in regard to adequacy of bowel prep and for detection of polyps.² Patients who followed low residue diets had statistically significantly less headaches, nausea, vomiting, and hunger. Very importantly, patients who followed low residue diets showed an increased willingness to repeat it, compared with those who followed a clear liquid diet (P less than .005; odds ratio, 2.23; 95% confidence interval, 1.28-3.89).²

What alternatives to GoLYTELY exist?

Another part of the bowel prep that patients struggle with is drinking a gallon of GoLYTELY (polyethylene glycol/electrolytes). Drinking that amount of this nasty stuff is never welcome.

There are a number of lower-volume alternatives that are as effective as GoLYTELY. Sarvepalli and colleagues did a retrospective study of 75,874 patients who had a colonoscopy in the Cleveland Clinic health system.³ The choice of bowel prep was not associated with adenoma detection.

Patients who lower volume preparations (2 quarts) SUPREP, MoviPrep, Osmoprep and HalfLytely had varying results of rates of inadequate bowel prep compared with patients who took GoLYTELY. Results for patients taking SUPREP and MoviPrep were statistically significantly better than for patients taking GoLYTELY. Results for patients taking OsmoPrep were not statistically different from those for patients taking GoLYTELY. Rates of inadequate bowel prep were statistically higher, meaning worse, for patients taking HalfLytely vs. patients taking GoLYTELY.³

Gu and colleagues did a prospective study of bowel prep outcomes from 4,339 colonoscopies, involving 75 different endoscopists.⁴ There was a wide range of bowel preps used, including low- and high-volume bowel preps. The low-volume preparations, SUPREP (P less than .001), MoviPrep (P less than .004) and MiraLAX with Gatorade (P less than .001), were superior to GoLYTELY for bowel cleansing. This was based on scoring via the Boston Bowel Preparation Scale. All were better tolerated than GoLYTELY.



Myth: All patients need a clear liquid diet and GoLYTELY for their bowel prep.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Soweid AM et al. A randomized single-blind trial of standard diet versus fiber-free diet with polyethylene glycol electrolyte solution for colonoscopy preparation. Endoscopy 2010;42:633-8.

2. Zhang X et al. Low-[residue] diet versus clear-liquid diet for bowel preparation before colonoscopy: meta-analysis and trial sequential analysis of randomized controlled trials. Gastrointest Endosc. 2020 Sep;92(3):508-18.

3. Sarvepalli S et al. Comparative effectiveness of commercial bowel preparations in ambulatory patients presenting for screening or surveillance colonoscopy. Dig Dis Sci. 2020 Jul 20. doi: 10.1007/s10620-020-06492-z.

4. Gu P et al. Comparing the real-world effectiveness of competing colonoscopy preparations: results of a prospective trial. Am J Gastroenterol. 2019;114(2):305-14.

A 61-year-old man is seen for a primary care visit. He has a history of colonic polyps (tubular adenoma) on two previous colonoscopies (at age 50 and 55). He has been on an appropriate 5-year schedule, but is overdue for his colonoscopy. He did not follow up with messages from his gastroenterologist for scheduling his colonoscopy last year. He explains he really hates the whole preparation for colonoscopy, but does realize he needs to follow up, and is willing to do so now. What do you recommend for colonoscopy prep?

A) Diet as usual until 5 p.m. day before, then clear liquid diet. Start GoLYTELY (1 gallon) night before procedure.

B) Low-fiber diet X2 days, clear liquid diet day before procedure, GoLYTELY (1 gallon) night before procedure.

C) Low residue diet X3 days, SUPREP the night before the procedure.

D) Low residue diet X2 days, followed by clear liquid diet the day before the procedure, SUPREP the night before the procedure.
 

It is common for patients to be reluctant to follow recommendations for colonoscopy due to dreading the prep. I would recommend choice C here, as the least difficult bowel preparation for colonoscopy.

Gastroenterologists are usually the ones to recommend the bowel prep that they want their patients to follow. When patients avoid needed colonoscopies because they hate the prep they are advised to take, I think it is good for primary care professionals to step in and discuss evidence-based alternatives.

Major diet change for several days before colonoscopy is difficult for many patients. Standard advice is that patients eat only low-fiber foods starting 3 days before the procedure. Patients are advised to switch to a completely clear liquid diet 1-2 days before the colonoscopy.

Are there more tolerable diets to offer patients?

Soweid and colleagues randomized 200 patients to a low residue diet for the three meals the day before colonoscopy vs. clear liquid diet.¹ The low residue diet allowed patients to eat meat, eggs, cheese, bread, rice, and ice cream. Not surprisingly, patients tolerated the low residue diet better with statistically significantly less nausea, vomiting, weakness, headache, sleep difficulties, and hunger. The patients in the low residue diet group also had better bowel prep than did those in the clear liquid diet group (81% vs. 52%, P less than 0.001).¹

In a recent meta- analysis, low residue diets were comparable to clear liquid diets in regard to adequacy of bowel prep and for detection of polyps.² Patients who followed low residue diets had statistically significantly less headaches, nausea, vomiting, and hunger. Very importantly, patients who followed low residue diets showed an increased willingness to repeat it, compared with those who followed a clear liquid diet (P less than .005; odds ratio, 2.23; 95% confidence interval, 1.28-3.89).²

What alternatives to GoLYTELY exist?

Another part of the bowel prep that patients struggle with is drinking a gallon of GoLYTELY (polyethylene glycol/electrolytes). Drinking that amount of this nasty stuff is never welcome.

There are a number of lower-volume alternatives that are as effective as GoLYTELY. Sarvepalli and colleagues did a retrospective study of 75,874 patients who had a colonoscopy in the Cleveland Clinic health system.³ The choice of bowel prep was not associated with adenoma detection.

Patients who lower volume preparations (2 quarts) SUPREP, MoviPrep, Osmoprep and HalfLytely had varying results of rates of inadequate bowel prep compared with patients who took GoLYTELY. Results for patients taking SUPREP and MoviPrep were statistically significantly better than for patients taking GoLYTELY. Results for patients taking OsmoPrep were not statistically different from those for patients taking GoLYTELY. Rates of inadequate bowel prep were statistically higher, meaning worse, for patients taking HalfLytely vs. patients taking GoLYTELY.³

Gu and colleagues did a prospective study of bowel prep outcomes from 4,339 colonoscopies, involving 75 different endoscopists.⁴ There was a wide range of bowel preps used, including low- and high-volume bowel preps. The low-volume preparations, SUPREP (P less than .001), MoviPrep (P less than .004) and MiraLAX with Gatorade (P less than .001), were superior to GoLYTELY for bowel cleansing. This was based on scoring via the Boston Bowel Preparation Scale. All were better tolerated than GoLYTELY.



Myth: All patients need a clear liquid diet and GoLYTELY for their bowel prep.
 

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Soweid AM et al. A randomized single-blind trial of standard diet versus fiber-free diet with polyethylene glycol electrolyte solution for colonoscopy preparation. Endoscopy 2010;42:633-8.

2. Zhang X et al. Low-[residue] diet versus clear-liquid diet for bowel preparation before colonoscopy: meta-analysis and trial sequential analysis of randomized controlled trials. Gastrointest Endosc. 2020 Sep;92(3):508-18.

3. Sarvepalli S et al. Comparative effectiveness of commercial bowel preparations in ambulatory patients presenting for screening or surveillance colonoscopy. Dig Dis Sci. 2020 Jul 20. doi: 10.1007/s10620-020-06492-z.

4. Gu P et al. Comparing the real-world effectiveness of competing colonoscopy preparations: results of a prospective trial. Am J Gastroenterol. 2019;114(2):305-14.

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.

Across this period of the pandemic, we’ve spent considerable attention focusing on adaptations to clinical care for pregnant and postpartum women across the board. From the start, this has included a shift to telemedicine for the majority of our patients who come to see us with psychiatric disorders either before, during, or after pregnancy.

Specific issues for perinatal patients since the early days of COVID-19 have included the shifts in women’s plans with respect to delivery as well as the limitation on women’s ability to configure the types of support that they had originally planned on with family, friends, and others during delivery. Telemedicine again helped, at least in part, to fill that void by having online digital support by individuals or groups for both pregnant and postpartum women. These supports were always available, but quickly scaled up during the first 6-9 months of the pandemic and have likely seen their greatest increase in participation in the history of support groups for pregnant and postpartum women.

Similarly, at our own center, we have seen a dramatic increase across the last 10 months in requests for consultation by women with psychiatric disorders who have hopes and plans to conceive, to those who are pregnant or post partum and who are trying to sustain emotional well-being despite the added burden of the pandemic. As we heard similar stories regarding interactions with perinatal patients from reproductive psychiatrists across the country, my colleagues and I had to set up an additional resource, Virtual Rounds at the Center for Women’s Mental Health at Massachusetts General Hospital, Boston, which has been mentioned in previous columns, which has only grown during the last 6 months of the pandemic. We have colleagues across the country joining us from 2 p.m. to 3 p.m. on Wednesdays after our own faculty rounds, where we perform case reviews of our own patients, and invite our colleagues to share cases that are then reviewed with expert panelists together with our own faculty in a collaborative environment. Feedback from the community of clinicians has indicated that these virtual rounds have been invaluable to their efforts in taking care of women with perinatal psychiatric issues, particularly during the pandemic.

Of particular note during consultations on our service is the number of women coming to see us for questions about the reproductive safety of the medications on which they are maintained. Hundreds of women present to the center each year for the most up-to-date information regarding the reproductive safety of the most commonly used psychiatric medications in reproductive-age women, including antidepressants (SSRIs, serotonin norepinephrine reuptake inhibitor), mood stabilizers, lithium, lamotrigine, and atypical antipsychotics, as well as other medicines used to treat symptoms that have been a particular issue during the pandemic, such as insomnia and anxiety (benzodiazepines, nonbenzodiazepines, sedative hypnotics, and medicines such as gabapentin).

While consultation regarding risk of fetal exposure to psychotropics has been the cornerstone of our clinical work for 25 years, it has taken on a particularly critical dimension during the pandemic given the wish that women stay euthymic during the pandemic to limit the possibility of patients needing to present in a clinical space that would increase their risk for COVID-19, and to also minimize their risk for postpartum depression. (Psychiatric disorder during pregnancy remains the strongest predictor of emergence or worsening of underlying illness during the postpartum period.)

It is also noteworthy that, during a pandemic year, publications in reproductive psychiatry have been numerous, and we continue to make an effort at our own center to keep up with this and to share with our colleagues our impression of that literature using the weekly blog at womensmentalhealth.org. Last year brought the largest audience to the blog and visits to womensmentalhealth.org in the history of our center.

A case recently at our center presents a unique opportunity to review a confusing question in reproductive psychiatry over the last 15 years. A woman with a longstanding history of mixed anxiety and depression recently came to see us on a regimen of escitalopram and low-dose benzodiazepine. She was doing well, and she and her husband of 4 years were hopeful about starting to try to conceive despite the pandemic. We reviewed the reproductive safety data of the medicines on which she was maintained and made plans to follow-up as her plans galvanized. She notified me several months later that she had become pregnant but had experienced an early miscarriage. The patient was obviously upset and, as she reflected on her decision to maintain treatment with SSRI during her attempts to conceive and across a very early pregnancy, she queried about the extent to which her SSRI use might have contributed to her miscarriage.

The question about the possible association of antidepressant use during pregnancy and increased risk for miscarriage goes back at least 15 years when there were reports of an increased risk of miscarriage in women taking SSRIs during pregnancy. In that early work, there was an apparent increase in miscarriage in women taking SSRIs relative to a control group, but the rate did not exceed the prevalence of miscarriage in the general population. Since those early reports, we are lucky to have had multiple investigators look very closely at this issue, including one meta-analysis of 11 studies done approximately 8 years ago that failed to show an increased risk of miscarriage in the setting of first trimester exposure to SSRIs.

What has been most problematic methodologically, however, has been the failure to account for the potential role of depression in models that predict risk. A subsequent large epidemiologic study from Denmark evaluating over a million women has looked at this question further. The authors found a slightly increased risk of spontaneous abortion associated with the use of antidepressants (12.0% in women with antidepressant exposure vs. 11.1% in women with no exposure). However, looking only at women with a diagnosis of depression, the adjusted risk ratio for spontaneous abortion after any antidepressant exposure was 1.00 (95% confidence interval, 0.80-1.24). Thus, the researchers concluded that exposure to depression – but not exposure to antidepressant – is associated with a slightly higher risk of miscarriage.

Even more recently, a follow-up study examining this question supports the large epidemiologic study by Kjaersgaard and colleagues. For most readers, this effectively answers this very important question for women about rates of miscarriage associated with fetal exposure to SSRIs.

For the patient who presented at the center, reassuring her with this information felt particularly good, especially within the context of the pandemic. After several months of trying to conceive, she again became pregnant and delivered without difficulty. What was palpable in that clinical scenario, as it relates to the practice of reproductive psychiatry during the pandemic, is the even-greater emotional valence that questions about using psychiatric medications during pregnancy has taken on across these past months. While attention and thoughtful consideration about the relative risks of using psychiatric medications during pregnancy should be standard clinical practice, the level of anxiety associated with decisions to sustain or to discontinue treatment during pregnancy seems to have increased for some patients during the pandemic.

Even as the COVID-19 vaccine initiative across the United States is rolled out, 2021 will continue to be a complicated time for women and families. We still need to be vigilant. In addition to screening for perinatal depression during pregnancy and the postpartum period, we should be equally mindful of screening and treating perinatal anxiety, particularly during this challenging time. The challenge to keep pregnant and postpartum women well is perhaps even greater now, 10 months into the pandemic, than it was when we were in crisis mode in March 2020. As clinicians, we need to mobilize the spectrum of both pharmacologic and nonpharmacologic treatment options to sustain emotional well-being among women planning to conceive as well as those who are pregnant or postpartum as we navigate our way to safer times.

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at obnews@mdedge.com.