Perspectives

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. STEPS for PPD is funded by the Marriott Foundation. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. STEPS for PPD is funded by the Marriott Foundation. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

The past year has been a challenging time for many, both at the local level and globally, with divisive undercurrents across many communities. Many times, the end of the year is an opportunity for reflection. As I reflect on the state of perinatal psychiatry in the new year, I see several evolving issues that I’d like to share in this first column of 2024.

In 2023, the American College of Obstetricians and Gynecologists published new recommendations meant to enhance the well-being of pregnant and postpartum women and families. A main message from discussion papers borne out of these recommendations was that as a field, we should be doing more than identifying perinatal illness. We should be screening women at risk for postpartum psychiatric illness and see that those suffering from posttraumatic stress disorder (PTSD) have access to care and “wrap-around services” from clinicians with varying expertise.

Screening is a primary way we identify patients at risk for psychiatric illness and also those who are suffering at the time of a screen. One problem I see in the near future is our disparate collection and management of data. When we look closely across health care systems, it’s not clear how screening data are captured, let alone managed. What is being done in one hospital system may be very different from what is being done elsewhere. Some clinicians are adopting digital platforms to identify those with postpartum depression, while others are practicing as they always have, either through a paper screening process or with queries as part of a clinical encounter.

Given this amalgam of methods for collecting and storing information, there does not appear to be a systematic way clinicians and researchers are recording whether women are meeting criteria for significant depressive symptoms or frank postpartum psychiatric illness. It is clear a more cohesive method for collection and management is needed to optimize the likelihood that next steps can be taken to get patients the care they need.

However, screening is only one part of the story. Certainly, in our own center, one of our greatest interests, both clinically and on the research side, is what happens after screening. Through our center’s initiation of the Screening and Treatment Enhancement for Postpartum Depression (STEPS for PPD) project funded by the Marriott Foundation, we are evaluating the outcomes of women who are screened at 6 weeks postpartum with significant depressive symptoms, and who are then given an opportunity to engage with a perinatal social worker who can assist with direct psychotherapy, arranging for referrals, and navigating care for a new mother.

What we are learning as we enroll women through the initial stages of STEPS for PPD is that screening and identifying women who likely suffer from PPD simply is not enough. In fact, once identified with a depression screening tool, women who are suffering from postpartum depression can be very challenging to engage clinically. What I am learning decades after starting to work with perinatal patients is that even with a screening system and effective tools for treatment of PPD, optimizing engagement with these depressed women seems a critical and understudied step on the road to optimizing positive clinical outcomes.

A recent study published in the Journal of Women’s Health explored gaps in care for perinatal depression and found that patients without a history of psychiatric illness prior to pregnancy were less likely to be screened for depression and 80% less likely to receive care if they developed depression compared with women with a previous history of psychiatric illness (J Womens Health (Larchmt). 2023 Oct;32[10]:1111-9).

That history may help women navigate to care, while women for whom psychiatric illness is a new experience may be less likely to engage, be referred for care, and receive appropriate treatment. The study indicates that, as a field, we must strive to ensure universal screening for depression in perinatal populations.

While we have always been particularly interested in populations of patients at highest risk for PPD, helping women at risk for PPD in the general population without a history of psychiatric illness is a large public health issue and will be an even larger undertaking. As women’s mental health is gaining more appropriate focus, both at the local level and even in the recent White House Initiative on Women’s Health Research, the focus has been on screening and developing new treatments.

We are not lacking in pharmacologic agents nor nonpharmacologic options as treatments for women experiencing PPD. Newer alternative treatments are being explored, such as transcranial magnetic stimulation (TMS) and even psychedelics as a potential therapy for PPD. But perhaps what we’ve learned in 2023 and as we move into a new year, is that the problem of tackling PPD is not only about having the right tools, but is about helping women navigate to the care that they need.

The COVID-19 pandemic brought with it an explosion of telehealth options that have enhanced the odds women can find support during such a challenging time; as society has returned to some semblance of normal, nearly all support groups for postpartum women have remained online.

When we set up Virtual Rounds at the Center for Women’s Mental Health at the beginning of the pandemic, I was struck by the community of colleagues at various stages of their careers dedicated to mitigating the suffering associated with perinatal psychiatric illness. As I’ve often said, it takes a village to care for these patients. We need help from colleagues with varying expertise — from lactation consultants, psychiatrists, psychologists, obstetricians, nurse practitioners, support group leaders, and a host of others — who can help reach these women.

At the end of the day, helping depressed women find resources is a challenge that we have not met in this country. We should be excited that we have so many treatment options to offer patients — whether it be a new first-in-class medication, TMS, or digital apps to ensure patients are receiving effective treatment. But there should also be a focus on reaching women who still need treatment, particularly in underserved communities where resources are sparse or nonexistent. Identifying the path to reaching these women where they are and getting them well should be a top priority in 2024.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. STEPS for PPD is funded by the Marriott Foundation. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Watto, here with America’s primary care physician, Dr. Paul Nelson Williams. Paul, are you ready to talk about some adrenal insufficiency? We had a great conversation with Dr. Atil Kargi, and I’d like you to start us off.

Paul N. Williams, MD: How about thinking about it? It’s a good place to start.

That’s one of the ways this episode changed my approach a little bit. I never really thought about the fact that many patients present for evaluation of adrenal insufficiency from gastroenterology clinics. It’s such a protean sort of nonspecific presentation. But if you have someone with chronic malaise and poor appetite and maybe unexplained weight loss, and your GI workup is not really leading you anywhere, it’s probably worth thinking about adrenal insufficiency. Even though primary adrenal insufficiency is pretty rare — we’re talking cases per millions — secondary adrenal insufficiency is actually fairly common. It’s probably worth thinking about and testing for more often than I have in the past. So for me, it’s having a lower threshold to start looking for it.

Dr. Watto: When it’s adrenal crisis, you probably think about it, but then it’s too late. Ideally, you would think about it before that happens. But the symptoms can be quite vague. The mineralocorticoid symptoms, like salt cravings, dizziness, near syncope, muscle cramps, might make me think of it because they sound more like something endocrine is going on. But if it’s just a little weight loss, a little fatigue, or a little nausea, that’s everybody.

Dr. Williams: Right. If a patient came to me saying, “I’m craving salt,” that might hasten the workup a little bit, but that’s not the typical presentation.

Dr. Watto: If you are going to check a cortisol level, you should really check it in the morning, between 7 AM and 9 AM. If you check it too early, it might not have peaked yet, so you might get a level that looks low. But if you had checked an hour or 2 later, it might have been above a threshold, and then you would know you could rule out the diagnosis. The cutoffs depend on your source:  < 3-5 µg/dL that early in the morning is pretty much diagnostic of adrenal insufficiency. If it’s > 15 µg/dL, that’s a pretty robust cortisol and the patient probably doesn’t have adrenal insufficiency. But if the level is between 5 µg/dL and 15 µg/dL, you’re in a gray zone, and that’s where you might think about doing a stimulation (stim) test.

Dr. Kargi gave us a quick and dirty version of the stim test. Paul, have you had a chance to try this yet?

Dr. Williams: I have not. Have you? I’m sure you’ve been just waiting for the chance.

Dr. Watto: I would love to do this. I don›t know whether I›m set up to do it in the office right now. But this is an aspirational goal for my practice, and I›m sure some physicians are set up in their office already to do it. You can give either intramuscular or subcutaneous cosyntropin 250 µg. You don›t even have to get a baseline cortisol level right before the injection. Let›s say the patient›s previous cortisol level was between 5 µg/dL and 15 µg/dL, so you weren›t sure about the diagnosis. You bring them back to the office one day, give them a shot of cosyntropin, and then 30-60 minutes later, have a random cortisol drawn. If it›s > 19 µg/dL, you›ve ruled out adrenal insufficiency. If it›s anything else, send them to an endocrinologist to sort it out. You might be able to make the diagnosis yourself doing that.

Any treatment pearls to leave the audience with?

Dr. Williams: I hope endocrinologists don›t take issue with this. I say this with respect and admiration, but it feels kind of vibe-based to me. Without a lab value to guide treatment, you are dependent on the patient telling you how they feel much of the time. You have to let their symptoms guide you. It is probably worth noting that because hydrocortisone has a relatively short half-life, within hours, in fact, you typically have to do twice-daily dosing, sometimes even three times daily dosing to get patients to where they feel okay. It sounds like there›s a fair amount of trial and error and some adjustments that you have to make depending on what›s going on with the patient at any given time. You land somewhere between a dose of 15-30 mg per day, but there will be some variability, even within an individual patient, depending on what›s going on with them from a physiologic standpoint.

Dr. Watto: They are going to take one dose in the morning and then a second dose in the afternoon, but they don’t want them to take it too late in the evening because it could cause insomnia, and you want to try to mimic physiologic levels as much as you can. Two thirds of the daily dose is given early in the morning and then another third of the daily dose later in the day if you are prescribing two times daily dosing.

And Dr. Kargi had a low threshold for doubling the dose. If the patient has a cold, double the dose for 2 or 3 days. With a high fever, triple the dose for a few days. If they are going for surgery, they are probably going to be getting some intravenous hydrocortisone while they’re in the hospital.

We really turned over like every stone we could possibly think of on this podcast. There were so many great pearls that we don’t have time to go through them all here. But we talked about steroid tapers and a lot more. You can check it out here.

Dr. Watto has disclosed no relevant financial relationships.

Dr. Williams has disclosed the following relevant financial relationships:Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: The CurbsidersReceived income in an amount equal to or greater than $250 from: The Curbsiders.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Often known as a “silent killer,” ascending thoracic aortic aneurysms (ATAAs) may grow asymptomatically until they rupture, at which point, mortality is over 90%.

But ATAAs may also carry a potential flip side: Apparent protection against the development of atherosclerotic plaque and by extension, for those who have one, a significantly reduced risk for coronary artery disease and myocardial infarction (MI).

“We noticed in the operating room that many patients we worked on who had an ATAA had pristine arteries, like a teenager’s,” said John Elefteriades, MD, William W.L. Glenn Professor of Cardiothoracic Surgery and former chief of cardiothoracic surgery at Yale University and Yale New Haven Hospital, New Haven, Connecticut. “The same was true of the femoral artery, which we use to hook up to the heart-lung machine.”

Elefteriades and colleagues have been investigating the implications of this association for more than two decades. Many of their studies are highlighted in a recent review of the evidence supporting the protective relationship between ATAAs and the development of atherosclerosis and the possible mechanisms driving the relationship.

“We see four different layers of protection,” said Sandip Mukherjee, MD, medical director of the Aortic Institute at Yale New Haven Hospital and a senior editor of the journal AORTA. Mukherjee collaborated with Elefteriades on many of the studies.

The first layer of protection is lower intima-media thickness, specifically, 0.131 mm lower than in individuals without an ATAA. “It may not seem like very much, but one point can actually translate into a 13%-15% decline in the rate of myocardial infarction or stroke,” Dr. Mukherjee said.

The second layer is lower levels of low-density lipoprotein (LDL) cholesterol. Lower LDL cholesterol levels (75 mg/dL) were associated with increased odds of ATAAs (odds ratio [OR], 1.21), whereas elevated levels (150 mg/dL and 200 mg/dL) were associated with decreased odds of ATAAs (OR, 0.62 and 0.29, respectively).

Lower calcification scores for the coronary arteries are the third layer of protection (6.73 vs 9.36 in one study).

The fourth protective layer is a significantly reduced prevalence of coronary artery disease. A study of individuals with ATAA compared to controls found 61 of those with ATAA had coronary artery disease vs 140 of controls, and 11 vs 83 had experienced an MI. Of note, patients with ATAAs were protected despite having higher body mass indices than controls.

Other MI risk factors such as age increased the risk even among those with an ATAA but, again, much less so than among controls; a multivariable binary logistic regression of data in the team’s review showed that patients with ATAAs were 298, 250, and 232 times less likely to have an MI than if they had a family history of MI, dyslipidemia, or hypertension, respectively.

Why the Protection?

The ligamentum arteriosum separates the ascending from the descending (thoracoabdominal) aorta. ATAAs, located above the ligamentum, tend to be pro-aneurysmal but anti-atherosclerotic. In the descending aorta, below the ligamentum, atherosclerotic aneurysms develop.

The differences between the two sections of the aorta originate in the germ layer in the embryo, Dr. Elefteriades said. “The fundamental difference in tissue of origin translates into marked differences in the character of aneurysms in the different aortic segments.”

What specifically underlies the reduced cardiovascular risk? “We don’t really know, but we think that there may be two possible etiologies,” Dr. Mukherjee said. One hypothesis involves transforming growth factor–beta (TGF-beta), which is overexpressed in patients with ATAA and seems to increase their vulnerability to aneurysms while also conferring protection from coronary disease risk.

Some studies have shown differences in cellular responses to TGF-beta between the thoracic and abdominal aorta, including collagen production and contractility. Others have shown that some patients who have had an MI have polymorphisms that decrease their levels of TGF-beta.

Furthermore, TGF-beta plays a key role in the development of the intimal layer, which could underpin the lack of intimal thickening in patients with ATAA.

But overall, studies have been mixed and challenging to interpret, Dr. Elefteriades and Dr. Mukherjee agreed. TGF-beta has multiple remodeling roles in the body, and it is difficult at this point to isolate its exact role in aortic disease.

Another hypothesis involves matrix metalloproteinases (MMPs), which are dysregulated in patients with ATAA and may confer some protection, Mukherjee said. Several studies have shown higher plasma levels of certain MMPs in patients with ATAAs. MMPs also were found to be elevated in the thoracic aortic walls of patients with ATAA who had an aortic dissection, as well as in the aortic smooth muscle cells in the intima and media.

In addition, some studies have shown increased levels of MMP-2 in the aortas of patients with ATAAs compared with patients with coronary artery disease.

Adding to the mix of possibilities, “We recently found a gene that’s dysregulated in our aneurysm patients that is very intimately related to atherosclerosis,” Dr. Elefteriades said. “But the work is too preliminary to say anything more at this point.”

“It would be fabulous to prove what it is causing this protection,” Dr. Mukherjee added. “But the truth is we don’t know. These are hypotheses.”

“The most important message from our work is that most clinicians need to dissociate an ATAA from the concept of atherosclerosis,” Dr. Elefteriades said. “The ascending aorta is not an atherosclerotic phenomenon.”

How to Manage Patients With ATAA

What does the distinct character of ATAAs mean for patient management? “Finding a drug to treat ATAAs — to prevent growth, rupture, or dissection — has been like a search for the Holy Grail,” Dr. Elefteriades said. “Statins are not necessary, as this is a non-atherosclerotic process. Although sporadic studies have reported beneficial effects from beta-blockers or angiotensin II receptor blockers (ARBs), this has often been based on ‘soft’ evidence, requiring a combination of outcome measures to achieve significance.”

That said, he noted, “The mainstay, common sense treatment is to keep blood pressure controlled. This is usually achieved by a beta-blocker and an ARB, even if the benefit is not via a direct biologic effect on the aneurysmal degenerative process, but via simple hemodynamics — discouraging rupture by keeping pressure in the aorta low.”

Dr. Mukherjee suggested that these patients should be referred to a specialty aneurysm center where their genes will be evaluated, and then the aneurysm will be followed very closely.

“If the aneurysm is larger than 4.5 cm, we screen the patient every single year, and if they have chest pain, we treat them the same way as we treat other aneurysms,” he said. “As a rule of thumb, if the aneurysm reaches 5 cm, it should come out, although the size at which this should happen may differ between 4.5 cm and 5.5 cm, depending on the patient’s body size.”

As for lifestyle management, Dr. Elefteriades said, “Protection from atherosclerosis and MI won’t go away after the aneurysm is removed. We think it’s in the body’s chemistry. But even though it’s very hard for those patients to have a heart attack, we don’t recommend they eat roast beef every night — although I do think they’d be protected from such lifestyle aberrations.”

For now, he added, “Our team is on a hunt to find a drug to treat ascending disease directly and effectively. We have ongoing laboratory experiments with two drugs undergoing investigation at some level. We hope to embark soon on clinical trials.”

‘A Milestone’

James Hamilton Black III, MD, vice chair of the writing committee for the 2022 American College of Cardiology/American Heart Association Aortic Disease Guideline and chief of Division of Vascular Surgery and Endovascular Therapy at Johns Hopkins Medicine, Baltimore, commented on the review and the concept of ATAA’s atherosclerotic protection.

“The association of ascending aortic aneurysms with a lower risk for MI is an interesting one, but it’s probably influenced, at least in part, by the patient population.” That population is at least partially curated since people are coming to an academic center. In addition, Dr. Black noted, “the patients with ATAAs are younger, and so age may be a confounding factor in the analyses. We wouldn’t expect them to have the same burden of atherosclerosis” as older patients.

Nevertheless, he said, “the findings speak to an emerging body of literature suggesting that although the aorta is a single organ, there are certainly different areas, and these would respond quite differently to environmental or genetic or heritable stressors. This isn’t surprising, and there probably are a lot of factors involved.”

Overall, he said, the findings underscore “the precision medicine approaches we need to take with patients with aortic diseases.”

In a commentary on the team’s review article, published in 2022, John G.T. Augoustides, MD, professor of anesthesiology and critical care at the Perelman School of Medicine in Philadelphia, Pennsylvania, suggested that ATAA’s “silver lining” could advance the understanding of thoracic aortic aneurysm (TAA) management, be integrated with the expanding horizons in hereditary thoracic aortic disease, and might be explored in the context of bicuspid aortic valve disease.

Highlighting the “relative absence” of atherosclerosis in ascending aortic aneurysms and its importance is a “milestone in our understanding,” he concluded. “It is likely that future advances in TAAs will be significantly influenced by this observation.”

Dr. Elefteriades, Dr. Mukherjee, and Dr. Black have no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

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

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

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

People are surprised when they learn I was an art history major in college. Most folks assume I had majored in biology or chemistry. Their assumption was based on strong odds. The U.S. Bureau of Labor Statistics reports that nearly half of all physicians practicing in this country were biology majors.

I headed off to college clueless about my future. I was hoping to succeed as a walk-on to the football team and beyond that I figured someone or something would guide me toward a career. Had you asked me, “physician” it would have been a definite “Never.”

I flirted with a psychology major, but after a semester I realized that the department was more interested in the behavior of rats rather than humans. I got an “easy A” in the intro to art history and that was the open door I was looking for.

By my senior year I was applying for fellowships to study in faraway places. However, the world situation in 1965 was unsettling for a young man in this country. I had had a strong high school science education and had continued to take a some science courses. Fortunately, I had banked just enough credits so that I could apply to medical school, again without really planning to become a physician.

Even during the sharpest turns in my circuitous path to becoming a small town pediatrician, including a year doing research in exercise physiology in Denmark, I never once regretted my years spent studying art history. I credit them with making me a more sensitive observer.

You can probably understand why I was intrigued by an article I recently read that described a program in which the radiology residents that the Brigham and Women’s Hospital in Boston take a year-long course in art history using the Art Museum at Harvard University as a resource. Titled “Seeing in Art and Medical Imaging,” the program is now 6 years old. Hyewon Hyun, MD, a radiologist and one of its cofounders, observes that “art is the starting point for in-depth conversations about medicine, humanity, and different ways of seeing the world.”

Radiology and dermatology are obviously the two specialties in which the physician relies most heavily on his or her powers of observation. However, every doctor can benefit from learning to really “see” what they are looking at. Looking and seeing are two very different activities. There is obviously the forest-from the-trees phenomenon. Can the physician in a hurried clinical situation muster up the discipline to shift focus back and forth from the lesion or painful body part to the entire patient and beyond? How is the parent responding to the child’s discomfort? How are they dressed? Does this wider view suggest some additional questions to ask that may help you understand how this patient or family will be able to cope with diagnosis or follow up with your treatment plan?

The art historian sees every object in its historical context. What has come before? How have the societal conditions influenced the artist choice of subject and use of materials? How has his or her emotions at the time of creation influenced his or her style? The astute physician must likewise see the patients and their complaints in the broader context of their emotional health and socioeconomic situation. This requires sensitive listening and careful observation.

One doesn’t have to major in art history or spend years roaming through the sometimes dark and dusty halls of the world’s museums to progress from being one who simply looks to a person who really sees the environment and its inhabitants. It is really a state of mind and a commitment to improvement.

As physicians, we often complain or sometimes brag about how many patients we “see” in a day. I fear that too often we mean “looked at.” How frequently did we make the effort to really see the patient?

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

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

The past year brought major changes in preventive standards for anxiety, HIV, and RSV along with new guidelines for the treatment of atrial fibrillation. For insight into the effect on internal medicine, we turned to Sarah Candler, MD, MPH, a Houston internist who specializes in the care of high-risk older adults.


Q: Which new prevention guidelines had the most impact on you over the past year?

A: I’m a primary care doctor, and most of the internal medicine updates that are interesting to me focus on how we can keep people from getting sick in the first place. That’s especially important in light of the fact that we had a decrease in life expectancy of 2 years [it finally rose slightly in 2022] and widening of the gender gap in life expectancy for men and women.

I’m excited to see new recommendations from the U.S. Preventive Services Task Force, including a new one about using PREP [pre-exposure prophylaxis] to preventively treat anyone who’s at risk for getting HIV. That’s a big one because it’s one of the first times that we’ve identified at-risk groups for screening based on social risk factors, not gender, age, or genetics.

The new recommendation is PREP for anyone who’s at risk for getting HIV because they have a partner with HIV, had an sexually transmitted infection in the last 6 months, or a history of inconsistent or no condom use with partners with unknown HIV status.

PREP therapy is something that most primary care physicians can either do or learn how to do pretty easily. But the treatment does require maintenance and monitoring.
 

Q: How firm is this recommendation?

A: The task force gives different grades for their recommendations based on how strong the evidence is. For the guidelines about PREP, they give a grade of A. That means this is top of the class: You should definitely do this.


Q: What are the best strategies to ask patients personal questions about their sex lives in order to evaluate their risk?

A: A lot of internal medicine physicians are getting pretty good at this. We see it as part of our job just the same way as we asked things like, “How often are you walking?” and “Have you been feeling down?”

There’s no one right way to have a conversation like that. But it’s key to say, as I do to my patients, that “I’m not here to judge anything. I am truly here to gather information and make recommendations to you as a partner in your care.”  
 

Q: What other guidelines made an impact in 2023?

A: The U.S. Preventive Services Task Force made a recommendation to screen adults aged 18-64 for anxiety, and this guidance got a B grade. [The task force said there’s not enough evidence to support routine anxiety screening in adults 65 and older.]

The new recommendations is a sign that we’re doing a better job at making treatment of those diseases more acceptable. This is also another example of the medical community recognizing that internal medicine physicians are pretty good at identifying and treating mental health.
 

Q: How do you figure out whether to treat depression/anxiety yourself or refer patients to specialists?

A: As a primary care physician, I feel comfortable diagnosing and managing some mental health disease in my own practice. There are FDA-approved medications for both anxiety and depression that are easily managed by a primary care physician.

And there’s something to the therapeutic relationship, to naming and identifying these conditions with your patients. Some patients feel a bit of relief just knowing that they have a diagnosis.
 

Q: What should internists know about the new CDC guidelines that promote discussing RSV vaccines with patients who are over 60?

A: The vaccines are recommended for folks who have underlying conditions like lung disease or heart disease. Those are the ones who end up getting really, really sick. There are two adult vaccines that are available, and there’s not a preference for one over the other.

The vaccines are both protein-based, like the old-school versions of vaccines, not the mRNA vaccines that we’ve all been hearing more about through COVID. Anybody who’s reluctant to take an mRNA vaccine can rest assured that the RSV is not protein-based. And they are single-dose vaccines, which is helpful.  
 

Q: What else should internists know about that was new in 2023?

A: I’m super excited about how cardiologists are thinking about atrial fibrillation. In 2023, the American College of Cardiology and the American Heart Association came up with a giant overhaul of how they look at atrial fibrillation. They classify it in stages and allows us to think about stopping it before it starts.

They’re talking about something they’re calling preclinical or subclinical atrial fibrillation, which you may detect on wearables like somebody’s watch or another tool used to monitor heart rate or exercise. It might be the first harbinger that there’s something wrong with the heart rate, and they may not even have symptoms of it. [A 2023 study in The New England Journal of Medicine linked the anticoagulant apixaban, or Eliquis, to a 37% lower risk of stroke and systemic embolism rates in older patients with subclinical atrial fibrillation but an 80% higher risk of major bleeding vs. aspirin therapy.]

And they’re now recommending early rhythm control.
 

Q: What does early rhythm control mean for patients and physicians?

A: For the longest time, we have thought about atrial fibrillation treatment in terms of rate control and not worrying too much about the rhythm. But now we recognize that it’s actually really important that we get the rhythm under control because physical changes to the heart can lead to permanent damage.

So now they’re recommending catheter ablation as first-line therapy in some patients as a class 1 recommendation because heart function is already decreased. Improving the ability of the heart to beat with a regular rhythm can lead to improvement of function. This was unheard of even 5 years ago.
 

Q: Should internists be more willing to refer patients with atrial fibrillation to cardiologists?

A: Yes, I think so. One of the biggest changes for me is that I am going to refer new diagnoses of atrial fibrillation to a cardiologist. And I’m going to ask patients if they have wearable devices because sometimes those things might tell me about something like subclinical atrial fibrillation.

Q: There’s also detailed data about atrial fibrillation risk factors, which include older age, smoking, sedentary lifestyle, alcohol use, diabetes, height, obesity, diabetes, and others. Is this information useful?

A: It’s a really great tool to have in the arsenal because it helps me have shared decision-making conversations with my patients in a way that’s much more convincing. A patient might say, “Why do you care if I drink so much? My liver levels are fine.” And I can say, “It’s going to be a risk factor for having problems with your heart.”

For better or worse, people really take the heart very seriously, I am an internal medicine physician, so I love all the organs equally. But man, people get pretty scared when you tell them something can affect their heart. So when I talk to patients about their risk factors, it’s going to really be helpful that I can remind them of the impact that some of these lifestyle behaviors can have on their heart health.
 

Dr. Candler has no disclosures.

Dear colleagues,

In this issue of Perspectives, we explore the impact of substance use on liver transplantation (LT). With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?

Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.

We welcome your thoughts on X at @AGA_GIHN.

Yale University

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.

Liver transplantation in the setting of alcohol-related liver disease

BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD

Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).

Duke University

The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.

Cleveland Clinic

One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.

The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
 

Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.

References

Tapper E. BMJ. 2018;362: k2817

Louvet A. Lancet Gastro Hep. 2022;7(5):416-25

Lee B. Gastroenterology. 2018;155:422-30

Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)

High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants

BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD

Marijuana remains a topic of controversy even amidst the ever-changing sociopolitical landscape, particularly in the United States.

Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.

University of Alabama at Birmingham

Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.^1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.² Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.³

University of Alabama at Birmingham

The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.² Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.

The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.⁴ 

The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.⁵ In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.

University of Alabama at Birmingham

The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.

Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.

REFERENCES

1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.

2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.

3. Page, RL. Circulation. 2020;142(10):e131-e152.

4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.

5. Zhu, J. Transplantation. 2018;102(3):433-439.

Dear colleagues,

In this issue of Perspectives, we explore the impact of substance use on liver transplantation (LT). With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?

Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.

We welcome your thoughts on X at @AGA_GIHN.

Yale University

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.

Liver transplantation in the setting of alcohol-related liver disease

BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD

Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).

Duke University

The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.

Cleveland Clinic

One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.

The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
 

Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.

References

Tapper E. BMJ. 2018;362: k2817

Louvet A. Lancet Gastro Hep. 2022;7(5):416-25

Lee B. Gastroenterology. 2018;155:422-30

Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)

High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants

BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD

Marijuana remains a topic of controversy even amidst the ever-changing sociopolitical landscape, particularly in the United States.

Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.

University of Alabama at Birmingham

Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.^1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.² Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.³

University of Alabama at Birmingham

The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.² Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.

The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.⁴ 

The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.⁵ In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.

University of Alabama at Birmingham

The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.

Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.

REFERENCES

1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.

2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.

3. Page, RL. Circulation. 2020;142(10):e131-e152.

4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.

5. Zhu, J. Transplantation. 2018;102(3):433-439.

Dear colleagues,

In this issue of Perspectives, we explore the impact of substance use on liver transplantation (LT). With recent dramatic improvements in treating hepatitis C, alcoholic liver disease has now become the leading indication for LT. Determining candidacy for a transplanted liver is a rigorous process and there has always been concern for relapse to alcohol use and its effect on the implanted graft. But, have we been too strict in restricting access in such patients?

Drs. Mitchell Mah’moud and John Aita explore this topic with a concise review of the current literature through an ethical lens. After alcohol, the most commonly used psychotropic drug is marijuana. Marijuana has traditionally been a barrier to candidacy for LT but, as with alcohol, should transplant centers relax this restriction, especially with ongoing legalization across the United States? Dr. Mohamed Shoreibah and colleagues explore this topic though a cogent review of the literature assessing the impact of marijuana use on liver transplant outcomes. We hope these essays will help your medical practice and ongoing advocacy for your patients.

We welcome your thoughts on X at @AGA_GIHN.

Yale University

Gyanprakash A. Ketwaroo, MD, MSc, is associate professor of medicine, Yale University, New Haven, Conn., and chief of endoscopy at West Haven VA Medical Center in Connecticut. He is an associate editor for GI & Hepatology News.

Liver transplantation in the setting of alcohol-related liver disease

BY MITCHELL MAH’MOUD, MD, FACG, AGAF, FAASLD, AND JOHN AITA, MD

Alcohol-related liver disease (ALD), with its subset of severe alcohol-associated hepatitis (SAH), currently accounts for most liver transplantation (LT) recipients in the United States. Patients with SAH, particularly those with a MELD-NA of at least 35, have a 70%-75% mortality rate within 6 months. The ethics of liver transplantation in the setting of SAH are complex and still controversial. With liver transplantation in general, there are more patients with various disorders listed for transplant than available organs. There may also be concern regarding a posttransplant return to harmful alcohol use leading to graft dysfunction or loss. Ultimately, in ethics terms, there is an inherent conflict between the values of beneficence (the obligation to act for an individual patient’s benefit) and justice (fair and equitable treatment of a society).

Duke University

The past decade has yielded supportive data depicting adequate posttransplant (LT) survival in select SAH patients. Previously, 6 months of alcohol sobriety was typically mandated by LT centers. Reasons for this requirement included (a) documentation of sobriety (including enrollment in an alcohol rehabilitation program) and (b) determination of maximal recovery (such that transplant may not be indicated). Present day information shows poor correlation between the 6-month alcohol sobriety period and reduced posttransplant alcohol use. In particular, the ACCELERATE-AH study, in which patients with severe alcoholic hepatitis underwent LT before 6 months of abstinence, demonstrated post-LT survival rates of 94% at 1 year and 84% at 3 years, similar to post-LT survival rates of other LT recipients. Although other factors may play into a transplant committee’s decision to require a period of sobriety before liver transplant evaluation, these data suggest that a “one size fits all” mandatory sobriety period prior to LT evaluation is now incongruent with normative medical practice.

Cleveland Clinic

One overarching principle of LT is that society provides organs to those patients with the greatest need. An inherent effect of listing select patients with SAH for liver transplant is that it potentially increases the wait time (and therefore the mortality risk) for other liver disease patients. Unfortunately, alcohol use disorder (AUD) has increased significantly in recent years among younger patients (from 2001 to 2013), and some patients may even be at greater risk of ALD (e.g., PNPLA3, TM6SF2, polymorphisms or post gastric bypass) with even mild/moderate use compared to other individuals . LT should not be considered a cure for AUD but rather a treatment for SAH that carries a high mortality rate but comparable post-LT survival to other indications for LT. Data from the ACCELERATE-AH trial revealed a cumulative incidence of any alcohol use at 1 year of approximately 25% and at 3 years of 34% for post-LT patients with SAH. This is roughly equivalent to reported disease recurrence rates of 10%-40% over 1-10 years post-LT for AIH, PBC and PSC and 7%-33% for MASLD. Despite these data, concern for reemergence of metabolic syndrome has never been an impediment when evaluating patients for LT due to end-stage liver disease from MASLD. LT centers may have a selection pathway that permits judicious transplant evaluation for SAH patients who, in the context of beneficence, are felt to greatly benefit from liver transplant in the near term (and are felt unlikely to recover without transplant) while, in the spirit of the ethical tenet of justice, also yield the best suitability for the donated organ (meaning the organ was put to good use with adequate graft survival). In this setting, a liver transplant program may utilize tools such as S-DAT, the PACT scoring system and TERS in identifying candidates with SAH for LT and those who are likely to relapse post-LT.

The optimal role of liver transplant in SAH patients is still emerging, but recent evidence suggests that the post-LT survival rate and alcohol-relapse rate appear to be acceptable. Nonetheless, the need to prevent harmful and sustained alcohol use post LT is vital since it is considered the strongest predictor of graft loss and death. Recent observations have also highlighted younger age and consumption of >10 drinks/day within 6 months of LT as predictors of sustained alcohol use post-LT. Hence, early identification of sustained alcohol use post-LT coupled with timely interventions based on abstinence-promoting behavioral and pharmacologic therapy should remain the goal of all transplant centers to avoid relapse and alcohol related deaths. In addition, incorporating addiction treatment centers into post-LT management should be considered standard of care to provide continued therapy for AUD in all patients post-LT. As in the DAA era of hepatitis C therapies, the role of LT in the setting of SAH may dwindle as emerging SAH-specific therapies evolve resulting in adequate transplant-free survival. Until then, it is beneficial to refine the guidelines periodically across all the UNOS regions on patient selection for LT in SAH, consistent with ethical principles of beneficence and justice. Finally, despite the concern about return to harmful drinking post LT, the need to destigmatize AUD and explain the purpose of LT for SAH through public education is vital.
 

Dr. Mah’moud is professor of medicine in the division of gastroenterology at Duke University School of Medicine, Durham, N.C., and a gastroenterologist with RMG Gastroenterology in North Carolina. Dr. Aita is gastroenterologist with Cleveland Clinic Indian River Hospital in Vero Beach, Fla. Dr. Mah’moud disclosed serving on the advisory board of CLDF, and receiving research support from Intercept Pharma and Gilead Scientific, but not in a capacity related to this article.

References

Tapper E. BMJ. 2018;362: k2817

Louvet A. Lancet Gastro Hep. 2022;7(5):416-25

Lee B. Gastroenterology. 2018;155:422-30

Shroff H. Hot Topics in Hepatology: Chicago ALF Debate. Clinical Liver Disease (2020 vol 16, No.5: 178-85)

High Stakes: Navigating the Hazy Intersection of Marijuana and Liver Transplants

BY JOVEN TRISTEZA, MD, THOMAS RULI, MD, AND MOHAMED SHOREIBAH, MD

Marijuana remains a topic of controversy even amidst the ever-changing sociopolitical landscape, particularly in the United States.

Marijuana is currently illegal at the federal level and is listed as a schedule I substance. However, marijuana for medical and recreational use has been legalized by several states, leading to an increase in its use. This unclear and disparate status of marijuana has created a smoky situation for patients being evaluated for liver transplant. Multiple studies have shown marijuana to provide medical benefits, while other studies in liver transplant patients have shown that it does not affect posttransplant outcomes. Those studies have helped inform decision-making for liver transplant selection committees across the country, where marijuana use is evaluated in the context of the patient’s medical and social history, as well as the history of other substance use. Though we do not encourage its use, we do not believe that marijuana use should be the singular reason to deny a patient listing for liver transplant.

University of Alabama at Birmingham

Marijuana has been studied extensively regarding its effects on the human body. The main compounds in marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. These compounds exhibit many effects that we observe clinically through the endocannabinoid system. Beneficial effects related to the gastrointestinal tract include relief from nausea and vomiting and stimulation of appetite in patients with anorexia. Other benefits outside the GI tract include alleviation of chronic pain and management of some forms of drug-resistant epilepsy. Ongoing studies are investigating the role of marijuana in other medical conditions.^1,2 At least equally notable are marijuana’s potential adverse effects, which include tachycardia, hypertension, agitation, nausea, psychosis, and hallucinations.² Marijuana may also increase the risk of heart failure, acute myocardial infarction, and stroke.³

University of Alabama at Birmingham

The exact effect of marijuana on the liver remains inconclusive. Receptors for endocannabinoids have been associated with steatosis and fibrosis in some studies. However, some evidence also suggests that marijuana may reduce inflammation in the liver.² Small, prospective studies have not been able to link marijuana use with hepatic laboratory abnormalities, and there is currently no significant association between marijuana and liver disease, injury, or cirrhosis. Of particular relevance to liver transplant recipients is marijuana’s effect on cytochrome P450 enzyme function, especially CYP3A4 which is the CYP class that metabolizes tacrolimus, a common immunosuppressant used in liver transplant patients. Marijuana inhibits CYP3A4 which could increase tacrolimus levels, potentially leading to morbidity. One strategy to mitigate this process is closer monitoring of tacrolimus levels for patients using marijuana.

The once-presumed increased risk of fungal infection — particularly Aspergillus — for liver transplant patients who use marijuana has been refuted. Furthermore, there have been concerns by liver transplant selection committees that marijuana use may be related to a greater risk of post–liver transplant noncompliance, infections, or even death. However, marijuana use on its own has not been associated with these concerns in the liver transplant population.⁴ 

The practice of excluding marijuana users from being listed for liver transplant does not appear to be evidence based. In a 2018 study focusing on US transplant centers, 40% of centers would not accept any marijuana use, and only 28% would list those who were taking medical marijuana for transplant. Interestingly, eight states have passed legislation prohibiting withholding transplant evaluation for marijuana users if it is solely based on their marijuana use.⁵ In the 5 years since that study was published, there have been major changes in the legality of marijuana. A future study of interest could assess how these changes have affected the position of transplant centers.

University of Alabama at Birmingham

The sociopolitical and transplant medicine worlds alike continue to adapt to the legalization of marijuana. While marijuana use is associated with adverse effects, its potential for benefit for a variety of medical conditions is an evolving area that has shown promise. It is therefore logical to view marijuana as a pharmacologic agent with potential for risks and benefits, but not necessarily a sole reason to exclude patients from listing for liver transplant. The current data are reassuring in that those who use marijuana and receive liver transplantation are not at higher risk of posttransplant complications, infections, or death when compared to those who do not use it. Should marijuana use exist in the context of substance use disorder or other behavioral and mental health issues, then the case warrants careful multidisciplinary evaluation prior to consideration for liver transplant. The aim of our discourse is not to encourage the use of marijuana in patients being considered for liver transplant but rather to discourage their exclusion from listing solely on the basis of marijuana use. In the pursuit of an equitable organ allocation system, our hope is that this work facilitates a more informed discussion and a change in policy in liver transplant programs that may still consider marijuana use an exclusion criterion.

Joven Tristeza, MD, and Thomas Ruli, MD, are residents in internal medicine at the University of Alabama at Birmingham; Mohamed Shoreibah, MD, is a specialist in gastroenterology and hepatology at the University of Alabama at Birmingham where he also serves on the faculty of the internal medicine residency program. The authors have no conflicts of interest.

REFERENCES

1. Cox, EJ. Pharmacology & Therapeutics. 2019;201:25-38.

2. Maselli, DB. Clinical Gastroenterology and Hepatology. 2021;19(9):1748-1758.e2.

3. Page, RL. Circulation. 2020;142(10):e131-e152.

4. Panchani, N. The American Journal of the Medical Sciences. 2023;365(2):115-120.

5. Zhu, J. Transplantation. 2018;102(3):433-439.

Until relatively recently, becoming a physician was a process in which the student began as an apprentice to an already skilled clinician. Eventually, both university- and hospital-based schools became part of the process, but an apprenticeship component persisted. In 1910, with the release of the Flexner Report, medical education here in the United States was revolutionized with a shift toward a more academic and scientific model already in use in Europe. While the path to becoming a physician grew more rigorous and science based when the students moved from the classroom and laboratory to the clinic and bedside, the process necessarily returned to its old one-on-one mentor-learner roots.

The venerable maxim of “See one — Do one — Teach one” that dominated my residency may still occasionally be whispered in the quiet corners of teaching hospitals, but I suspect concerns about risk management have discouraged its frequent application in hands-on situations. The development of artificial intelligence–driven mannequins may have finally relegated this remnant of an old cowboy (and girl) procedure-acquisition strategy to the dusty closet of medical education history.

However, when it comes to non–procedure based learning in clinic and hospital settings, the process continues to be one in which the inexperienced are expected to learn by observing their more experienced (sometimes only slightly more experienced) mentors. There may be some mini “lectures” on the fly during rounds explaining the rationale behind what the learner is observing, but “teaching” is still dominated by “Watch this — Try it when it’s your turn — Then we’ll tell you how you did.”

A recent survey in the journal Hospital Pediatrics reviewed in AAP News suggests that there is a problem with feedback, the final step in this three-step process. The investigators surveyed 52 residents and 21 fellows using a scale developed for industrial applications and found that, with the exception of delivery, the fellows scored better than residents in the feedback process. In interviews with a small subgroup of eight residents, the researchers learned that the two consistent impediments to obtaining feedback were 1) that the hectic pace of patient care placed a limit on opportunities (not surprising) and 2) a culture emphasizing “a positive, nurturing environment may have led physicians to avoid giving constructive criticism because it might hurt resident’s feelings.”

I have a friend who has held human resource (HR) positions in two good-sized teaching hospital systems. He certainly agrees with the time limitations component. He has also been involved in several cases in which trainees have accused senior physicians of harassment and unprofessional behavior because learners took issue with the manner in which they had been given feedback on their performance. One wonders if the institution(s) surveyed in this recent study had already experienced similar cases of discontent and have reacted by being so polite that feedback now lacks a feel of authenticity. This was a very small study, and it is hard to know how applicable the findings would be in a national sample, but I suspect there are more than a few teaching institutions in which kid gloves have become fashionable attire.

As my friend pointed out to me, substantial “generational differences” exist in many work places. Different generations may hold competing value systems when it comes to how feedback should be, and should not be, delivered.

None of us were trained in how to deliver a performance evaluation and feedback regardless of whether it was with one or two rushed sentences on a sprint from room to room on morning rounds or a more relaxed sit-down at the end of a rotation. We tend to lean on our own experiences of receiving feedback from our parents, from coaches, and most often from the models we observed as we came up through the hierarchy of medical training.

Feedback is a tightrope we must all walk along, and we must be acutely aware of the background and expectations of the recipients of well-meaning constructive criticism. I found it refreshing to learn that at least one small population of the trainees may be willing, and even eager, to receive honest feedback even though it sometimes may come with a hard edge.
 

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

Until relatively recently, becoming a physician was a process in which the student began as an apprentice to an already skilled clinician. Eventually, both university- and hospital-based schools became part of the process, but an apprenticeship component persisted. In 1910, with the release of the Flexner Report, medical education here in the United States was revolutionized with a shift toward a more academic and scientific model already in use in Europe. While the path to becoming a physician grew more rigorous and science based when the students moved from the classroom and laboratory to the clinic and bedside, the process necessarily returned to its old one-on-one mentor-learner roots.

The venerable maxim of “See one — Do one — Teach one” that dominated my residency may still occasionally be whispered in the quiet corners of teaching hospitals, but I suspect concerns about risk management have discouraged its frequent application in hands-on situations. The development of artificial intelligence–driven mannequins may have finally relegated this remnant of an old cowboy (and girl) procedure-acquisition strategy to the dusty closet of medical education history.

However, when it comes to non–procedure based learning in clinic and hospital settings, the process continues to be one in which the inexperienced are expected to learn by observing their more experienced (sometimes only slightly more experienced) mentors. There may be some mini “lectures” on the fly during rounds explaining the rationale behind what the learner is observing, but “teaching” is still dominated by “Watch this — Try it when it’s your turn — Then we’ll tell you how you did.”

A recent survey in the journal Hospital Pediatrics reviewed in AAP News suggests that there is a problem with feedback, the final step in this three-step process. The investigators surveyed 52 residents and 21 fellows using a scale developed for industrial applications and found that, with the exception of delivery, the fellows scored better than residents in the feedback process. In interviews with a small subgroup of eight residents, the researchers learned that the two consistent impediments to obtaining feedback were 1) that the hectic pace of patient care placed a limit on opportunities (not surprising) and 2) a culture emphasizing “a positive, nurturing environment may have led physicians to avoid giving constructive criticism because it might hurt resident’s feelings.”

I have a friend who has held human resource (HR) positions in two good-sized teaching hospital systems. He certainly agrees with the time limitations component. He has also been involved in several cases in which trainees have accused senior physicians of harassment and unprofessional behavior because learners took issue with the manner in which they had been given feedback on their performance. One wonders if the institution(s) surveyed in this recent study had already experienced similar cases of discontent and have reacted by being so polite that feedback now lacks a feel of authenticity. This was a very small study, and it is hard to know how applicable the findings would be in a national sample, but I suspect there are more than a few teaching institutions in which kid gloves have become fashionable attire.

As my friend pointed out to me, substantial “generational differences” exist in many work places. Different generations may hold competing value systems when it comes to how feedback should be, and should not be, delivered.

None of us were trained in how to deliver a performance evaluation and feedback regardless of whether it was with one or two rushed sentences on a sprint from room to room on morning rounds or a more relaxed sit-down at the end of a rotation. We tend to lean on our own experiences of receiving feedback from our parents, from coaches, and most often from the models we observed as we came up through the hierarchy of medical training.

Feedback is a tightrope we must all walk along, and we must be acutely aware of the background and expectations of the recipients of well-meaning constructive criticism. I found it refreshing to learn that at least one small population of the trainees may be willing, and even eager, to receive honest feedback even though it sometimes may come with a hard edge.
 

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

Until relatively recently, becoming a physician was a process in which the student began as an apprentice to an already skilled clinician. Eventually, both university- and hospital-based schools became part of the process, but an apprenticeship component persisted. In 1910, with the release of the Flexner Report, medical education here in the United States was revolutionized with a shift toward a more academic and scientific model already in use in Europe. While the path to becoming a physician grew more rigorous and science based when the students moved from the classroom and laboratory to the clinic and bedside, the process necessarily returned to its old one-on-one mentor-learner roots.

The venerable maxim of “See one — Do one — Teach one” that dominated my residency may still occasionally be whispered in the quiet corners of teaching hospitals, but I suspect concerns about risk management have discouraged its frequent application in hands-on situations. The development of artificial intelligence–driven mannequins may have finally relegated this remnant of an old cowboy (and girl) procedure-acquisition strategy to the dusty closet of medical education history.

However, when it comes to non–procedure based learning in clinic and hospital settings, the process continues to be one in which the inexperienced are expected to learn by observing their more experienced (sometimes only slightly more experienced) mentors. There may be some mini “lectures” on the fly during rounds explaining the rationale behind what the learner is observing, but “teaching” is still dominated by “Watch this — Try it when it’s your turn — Then we’ll tell you how you did.”

A recent survey in the journal Hospital Pediatrics reviewed in AAP News suggests that there is a problem with feedback, the final step in this three-step process. The investigators surveyed 52 residents and 21 fellows using a scale developed for industrial applications and found that, with the exception of delivery, the fellows scored better than residents in the feedback process. In interviews with a small subgroup of eight residents, the researchers learned that the two consistent impediments to obtaining feedback were 1) that the hectic pace of patient care placed a limit on opportunities (not surprising) and 2) a culture emphasizing “a positive, nurturing environment may have led physicians to avoid giving constructive criticism because it might hurt resident’s feelings.”

I have a friend who has held human resource (HR) positions in two good-sized teaching hospital systems. He certainly agrees with the time limitations component. He has also been involved in several cases in which trainees have accused senior physicians of harassment and unprofessional behavior because learners took issue with the manner in which they had been given feedback on their performance. One wonders if the institution(s) surveyed in this recent study had already experienced similar cases of discontent and have reacted by being so polite that feedback now lacks a feel of authenticity. This was a very small study, and it is hard to know how applicable the findings would be in a national sample, but I suspect there are more than a few teaching institutions in which kid gloves have become fashionable attire.

As my friend pointed out to me, substantial “generational differences” exist in many work places. Different generations may hold competing value systems when it comes to how feedback should be, and should not be, delivered.

None of us were trained in how to deliver a performance evaluation and feedback regardless of whether it was with one or two rushed sentences on a sprint from room to room on morning rounds or a more relaxed sit-down at the end of a rotation. We tend to lean on our own experiences of receiving feedback from our parents, from coaches, and most often from the models we observed as we came up through the hierarchy of medical training.

Feedback is a tightrope we must all walk along, and we must be acutely aware of the background and expectations of the recipients of well-meaning constructive criticism. I found it refreshing to learn that at least one small population of the trainees may be willing, and even eager, to receive honest feedback even though it sometimes may come with a hard edge.
 

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

A recent Reuters article reported that the manufacturer of the leading antiobesity medication semaglutide (Wegovy) “showers money on U.S. obesity doctors.”

Hello. I’d like to be showered.

According to the article, Novo Nordisk, Wegovy/Ozempic manufacturer, paid medical professionals $25.8 million in “fees and expenses” over a decade.

I think all doctors — who spend a decade of their life in training only to emerge with thousands of dollars in debt — would like to be similarly compensated for their expertise.

Yet, many of us forgo lucrative private practices or industry jobs to work at academic medical centers because we wish to pursue our original mission: To provide the best patient care possible.

Fulfilling this mission in today’s “sickcare” system means being more than a clinician. We become researchers, educators, advocates, mentors, consultants, and advisors. We do so because the system compels us to find other ways to provide quality health care, outside of clinic walls. These ways often include:

• Educating the public through media, social media, or community events.
• Training students, residents, and fellows on the latest medical knowledge.
• Advising industry innovators and entrepreneurs who seek our expertise.

Personally, I engaged in these activities because working 8-5 seeing 20 patients a day wasn’t enough. I wanted to help more people, more quickly. When I was faced with these opportunities, I was excited to say “yes” and never thought to ask for compensation because I didn’t want to seem ungrateful.

Eventually, I learned to ask for compensation.

And then I learned to decide my value.

The Reuters article reports that obesity medicine experts Drs. Lee Kaplan, Donna Ryan, Ania Jastreboff, and Jamy Ard were paid thousands of dollars in consulting fees over a decade. This industry-to-physician relationship should be celebrated because:

• Industries should consult experts in the field.
• These leaders have dedicated decades of their lives to understanding and solving the obesity epidemic.
• This collaboration has resulted in a therapeutic option that is changing lives. 

If there is anything to criticize, it should be:

• The expectation that medical expertise should be free.Wegovy’s manufacturer is worth $403 billion, and the experts are valued at less than 0.1% of that figure.
• The lack of context.
• Some celebrity doctors can earn $300,000 in just one consult. Other medical or surgical specialties are valued at 100 times more than obesity specialists. 
• The false dichotomy.
• Just because money is involved, it doesn’t mean the product is invalid.

Industry and physician relationships have long been examined. Such financial relationships are always disclosed (eg, at conferences, in publications). The Sunshine Act of 2010 and Open Payments provide the necessary transparency for people to decide for themselves whether there were financial incentives or potential conflicts of interest.

We should also take it a step further and ask ourselves: Do conflicts of interest require us to dismiss the end result? In other words, just because the pharmaceutical industry pays these doctors for their time and expertise, does that mean their life’s work is wrong, or that the drug isn’t effective?

In the case of obesity, Wegovy speaks for itself. Remember that the manufacturer stopped advertising. When a disease finally has a treatment, it does not need promoters or salespersons. Just speak to any person with obesity.

Ultimately, I see three main takeaways from Reuters’ reporting:

• The weight loss industry needs more obesity medicine experts. 
• We should value ourselves more.
• When people with resources work with people who have the commitment, knowledge, and experience, we can find a solution that saves lives. 

Dr. Tchang received $5525 in 2022 in consulting fees from Novo Nordisk. She plans to ask for more. She also disclosed ties with Gelesis.

A version of this article appeared on Medscape.com.

A recent Reuters article reported that the manufacturer of the leading antiobesity medication semaglutide (Wegovy) “showers money on U.S. obesity doctors.”

Hello. I’d like to be showered.

According to the article, Novo Nordisk, Wegovy/Ozempic manufacturer, paid medical professionals $25.8 million in “fees and expenses” over a decade.

I think all doctors — who spend a decade of their life in training only to emerge with thousands of dollars in debt — would like to be similarly compensated for their expertise.

Yet, many of us forgo lucrative private practices or industry jobs to work at academic medical centers because we wish to pursue our original mission: To provide the best patient care possible.

Fulfilling this mission in today’s “sickcare” system means being more than a clinician. We become researchers, educators, advocates, mentors, consultants, and advisors. We do so because the system compels us to find other ways to provide quality health care, outside of clinic walls. These ways often include:

• Educating the public through media, social media, or community events.
• Training students, residents, and fellows on the latest medical knowledge.
• Advising industry innovators and entrepreneurs who seek our expertise.

Personally, I engaged in these activities because working 8-5 seeing 20 patients a day wasn’t enough. I wanted to help more people, more quickly. When I was faced with these opportunities, I was excited to say “yes” and never thought to ask for compensation because I didn’t want to seem ungrateful.

Eventually, I learned to ask for compensation.

And then I learned to decide my value.

The Reuters article reports that obesity medicine experts Drs. Lee Kaplan, Donna Ryan, Ania Jastreboff, and Jamy Ard were paid thousands of dollars in consulting fees over a decade. This industry-to-physician relationship should be celebrated because:

• Industries should consult experts in the field.
• These leaders have dedicated decades of their lives to understanding and solving the obesity epidemic.
• This collaboration has resulted in a therapeutic option that is changing lives. 

If there is anything to criticize, it should be:

• The expectation that medical expertise should be free.Wegovy’s manufacturer is worth $403 billion, and the experts are valued at less than 0.1% of that figure.
• The lack of context.
• Some celebrity doctors can earn $300,000 in just one consult. Other medical or surgical specialties are valued at 100 times more than obesity specialists. 
• The false dichotomy.
• Just because money is involved, it doesn’t mean the product is invalid.

Industry and physician relationships have long been examined. Such financial relationships are always disclosed (eg, at conferences, in publications). The Sunshine Act of 2010 and Open Payments provide the necessary transparency for people to decide for themselves whether there were financial incentives or potential conflicts of interest.

We should also take it a step further and ask ourselves: Do conflicts of interest require us to dismiss the end result? In other words, just because the pharmaceutical industry pays these doctors for their time and expertise, does that mean their life’s work is wrong, or that the drug isn’t effective?

In the case of obesity, Wegovy speaks for itself. Remember that the manufacturer stopped advertising. When a disease finally has a treatment, it does not need promoters or salespersons. Just speak to any person with obesity.

Ultimately, I see three main takeaways from Reuters’ reporting:

• The weight loss industry needs more obesity medicine experts. 
• We should value ourselves more.
• When people with resources work with people who have the commitment, knowledge, and experience, we can find a solution that saves lives. 

Dr. Tchang received $5525 in 2022 in consulting fees from Novo Nordisk. She plans to ask for more. She also disclosed ties with Gelesis.

A version of this article appeared on Medscape.com.

A recent Reuters article reported that the manufacturer of the leading antiobesity medication semaglutide (Wegovy) “showers money on U.S. obesity doctors.”

Hello. I’d like to be showered.

According to the article, Novo Nordisk, Wegovy/Ozempic manufacturer, paid medical professionals $25.8 million in “fees and expenses” over a decade.

I think all doctors — who spend a decade of their life in training only to emerge with thousands of dollars in debt — would like to be similarly compensated for their expertise.

Yet, many of us forgo lucrative private practices or industry jobs to work at academic medical centers because we wish to pursue our original mission: To provide the best patient care possible.

Fulfilling this mission in today’s “sickcare” system means being more than a clinician. We become researchers, educators, advocates, mentors, consultants, and advisors. We do so because the system compels us to find other ways to provide quality health care, outside of clinic walls. These ways often include:

• Educating the public through media, social media, or community events.
• Training students, residents, and fellows on the latest medical knowledge.
• Advising industry innovators and entrepreneurs who seek our expertise.

Personally, I engaged in these activities because working 8-5 seeing 20 patients a day wasn’t enough. I wanted to help more people, more quickly. When I was faced with these opportunities, I was excited to say “yes” and never thought to ask for compensation because I didn’t want to seem ungrateful.

Eventually, I learned to ask for compensation.

And then I learned to decide my value.

The Reuters article reports that obesity medicine experts Drs. Lee Kaplan, Donna Ryan, Ania Jastreboff, and Jamy Ard were paid thousands of dollars in consulting fees over a decade. This industry-to-physician relationship should be celebrated because:

• Industries should consult experts in the field.
• These leaders have dedicated decades of their lives to understanding and solving the obesity epidemic.
• This collaboration has resulted in a therapeutic option that is changing lives. 

If there is anything to criticize, it should be:

• The expectation that medical expertise should be free.Wegovy’s manufacturer is worth $403 billion, and the experts are valued at less than 0.1% of that figure.
• The lack of context.
• Some celebrity doctors can earn $300,000 in just one consult. Other medical or surgical specialties are valued at 100 times more than obesity specialists. 
• The false dichotomy.
• Just because money is involved, it doesn’t mean the product is invalid.

Industry and physician relationships have long been examined. Such financial relationships are always disclosed (eg, at conferences, in publications). The Sunshine Act of 2010 and Open Payments provide the necessary transparency for people to decide for themselves whether there were financial incentives or potential conflicts of interest.

We should also take it a step further and ask ourselves: Do conflicts of interest require us to dismiss the end result? In other words, just because the pharmaceutical industry pays these doctors for their time and expertise, does that mean their life’s work is wrong, or that the drug isn’t effective?

In the case of obesity, Wegovy speaks for itself. Remember that the manufacturer stopped advertising. When a disease finally has a treatment, it does not need promoters or salespersons. Just speak to any person with obesity.

Ultimately, I see three main takeaways from Reuters’ reporting:

• The weight loss industry needs more obesity medicine experts. 
• We should value ourselves more.
• When people with resources work with people who have the commitment, knowledge, and experience, we can find a solution that saves lives. 

Dr. Tchang received $5525 in 2022 in consulting fees from Novo Nordisk. She plans to ask for more. She also disclosed ties with Gelesis.

A version of this article appeared on Medscape.com.

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .