Opinion

My medical office in Cincinnati isn’t in the best part of town. It’s next to a busy bus stop, a block from the medical center, behind a McDonald’s, and next to a convenience store. Ohio is the epicenter for the opioid crisis, and there are three drug treatment centers within a mile of my office. Hungry “ghosts” drift through my office parking lot. (See “In the Realm of Hungry Ghosts – Introduction,” Gabor Maté, MD).

I tell you these things because it helps me to rationalize how I missed something one day that should have been obvious to me at the time. I’ve been grappling for some time with my belated realization of what I may have seen that day, and what I wished I had done in response.

I mentioned that my office is next to a convenience store, and I’ve been a regular customer there over the years. One day when I was in there, paying for something, a swaggering guy in his 50s – reddish comb-over, glasses, muscular – came in with a young blond girl. I guessed her to be his 14- or 15-year-old daughter. I paid for my purchase, and glanced over to see them standing at the ice cream counter. That’s nice, I thought, he is buying his daughter an ice cream cone. I used to buy my kids ice cream here. But then I noticed that the girl was trembling, quaking really, and crying softly. I stopped, and noticed that the man had his arm around her. His grip was way too tight and his arm was draped too low. I stepped back, and I swear I saw blood running down from her scalp and behind her ear.

coldsnowstorm/iStock/Getty Images Plus

Good grief, this isn’t right! I was paralyzed. Maybe she wasn’t his daughter. Maybe she was some sort of a captive, a victim? Maybe he had just beaten her and was now rewarding her? I knew something was wrong, and I did not know what to do. The store was busy, and I looked around at the other people there but no one else seemed to notice her unhappiness or the blood.

I did not say ‘unhand that girl.’ I did not say ‘I am a doctor, can I help you?’ I did not even ask her if she was OK. Instead, I walked back next door to my office and started making phone calls. I called the police and got a recording. Eventually I spoke to someone, but I had no proof. I was angry with myself for not taking a picture – my phone was in my pocket. Did I observe a crime being committed? Were there other witnesses? The sorry truth is that I had walked away, the man and girl were gone, and any others who may have seen what I saw also had left. This could have been a case of human trafficking, I said, and recommended that they follow up with the store and any evidence that they could pick up from its video cameras. It’s been nearly a year, and I have heard nothing.

My failure to act at the time has tormented me for months. I have sought out more information about human trafficking, and the event I witnessed is what human trafficking looks like.


Maybe that girl was his daughter. Maybe she fell and cut her head. Maybe I was jumping to conclusions. But I am never again going to walk away from a girl who is clearly injured and potentially in trouble. I am going ask that girl if she’s OK, I am going to take a picture, and I am going to dial 911 immediately.

Don’t be a failure like me. Call 911. Take a picture. Take the risk, embarrass yourself or you will be tormented by your conscience as I am. We all must all step up, learn the signs of potential human trafficking, and stop allowing our young people to be fed to monsters.

The Centers for Disease Control and Prevention offers information and resources on human trafficking at www.cdc.gov/violenceprevention/sexualviolence/trafficking.html.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

My medical office in Cincinnati isn’t in the best part of town. It’s next to a busy bus stop, a block from the medical center, behind a McDonald’s, and next to a convenience store. Ohio is the epicenter for the opioid crisis, and there are three drug treatment centers within a mile of my office. Hungry “ghosts” drift through my office parking lot. (See “In the Realm of Hungry Ghosts – Introduction,” Gabor Maté, MD).

I tell you these things because it helps me to rationalize how I missed something one day that should have been obvious to me at the time. I’ve been grappling for some time with my belated realization of what I may have seen that day, and what I wished I had done in response.

I mentioned that my office is next to a convenience store, and I’ve been a regular customer there over the years. One day when I was in there, paying for something, a swaggering guy in his 50s – reddish comb-over, glasses, muscular – came in with a young blond girl. I guessed her to be his 14- or 15-year-old daughter. I paid for my purchase, and glanced over to see them standing at the ice cream counter. That’s nice, I thought, he is buying his daughter an ice cream cone. I used to buy my kids ice cream here. But then I noticed that the girl was trembling, quaking really, and crying softly. I stopped, and noticed that the man had his arm around her. His grip was way too tight and his arm was draped too low. I stepped back, and I swear I saw blood running down from her scalp and behind her ear.

coldsnowstorm/iStock/Getty Images Plus

Good grief, this isn’t right! I was paralyzed. Maybe she wasn’t his daughter. Maybe she was some sort of a captive, a victim? Maybe he had just beaten her and was now rewarding her? I knew something was wrong, and I did not know what to do. The store was busy, and I looked around at the other people there but no one else seemed to notice her unhappiness or the blood.

I did not say ‘unhand that girl.’ I did not say ‘I am a doctor, can I help you?’ I did not even ask her if she was OK. Instead, I walked back next door to my office and started making phone calls. I called the police and got a recording. Eventually I spoke to someone, but I had no proof. I was angry with myself for not taking a picture – my phone was in my pocket. Did I observe a crime being committed? Were there other witnesses? The sorry truth is that I had walked away, the man and girl were gone, and any others who may have seen what I saw also had left. This could have been a case of human trafficking, I said, and recommended that they follow up with the store and any evidence that they could pick up from its video cameras. It’s been nearly a year, and I have heard nothing.

My failure to act at the time has tormented me for months. I have sought out more information about human trafficking, and the event I witnessed is what human trafficking looks like.


Maybe that girl was his daughter. Maybe she fell and cut her head. Maybe I was jumping to conclusions. But I am never again going to walk away from a girl who is clearly injured and potentially in trouble. I am going ask that girl if she’s OK, I am going to take a picture, and I am going to dial 911 immediately.

Don’t be a failure like me. Call 911. Take a picture. Take the risk, embarrass yourself or you will be tormented by your conscience as I am. We all must all step up, learn the signs of potential human trafficking, and stop allowing our young people to be fed to monsters.

The Centers for Disease Control and Prevention offers information and resources on human trafficking at www.cdc.gov/violenceprevention/sexualviolence/trafficking.html.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

My medical office in Cincinnati isn’t in the best part of town. It’s next to a busy bus stop, a block from the medical center, behind a McDonald’s, and next to a convenience store. Ohio is the epicenter for the opioid crisis, and there are three drug treatment centers within a mile of my office. Hungry “ghosts” drift through my office parking lot. (See “In the Realm of Hungry Ghosts – Introduction,” Gabor Maté, MD).

I tell you these things because it helps me to rationalize how I missed something one day that should have been obvious to me at the time. I’ve been grappling for some time with my belated realization of what I may have seen that day, and what I wished I had done in response.

I mentioned that my office is next to a convenience store, and I’ve been a regular customer there over the years. One day when I was in there, paying for something, a swaggering guy in his 50s – reddish comb-over, glasses, muscular – came in with a young blond girl. I guessed her to be his 14- or 15-year-old daughter. I paid for my purchase, and glanced over to see them standing at the ice cream counter. That’s nice, I thought, he is buying his daughter an ice cream cone. I used to buy my kids ice cream here. But then I noticed that the girl was trembling, quaking really, and crying softly. I stopped, and noticed that the man had his arm around her. His grip was way too tight and his arm was draped too low. I stepped back, and I swear I saw blood running down from her scalp and behind her ear.

coldsnowstorm/iStock/Getty Images Plus

Good grief, this isn’t right! I was paralyzed. Maybe she wasn’t his daughter. Maybe she was some sort of a captive, a victim? Maybe he had just beaten her and was now rewarding her? I knew something was wrong, and I did not know what to do. The store was busy, and I looked around at the other people there but no one else seemed to notice her unhappiness or the blood.

I did not say ‘unhand that girl.’ I did not say ‘I am a doctor, can I help you?’ I did not even ask her if she was OK. Instead, I walked back next door to my office and started making phone calls. I called the police and got a recording. Eventually I spoke to someone, but I had no proof. I was angry with myself for not taking a picture – my phone was in my pocket. Did I observe a crime being committed? Were there other witnesses? The sorry truth is that I had walked away, the man and girl were gone, and any others who may have seen what I saw also had left. This could have been a case of human trafficking, I said, and recommended that they follow up with the store and any evidence that they could pick up from its video cameras. It’s been nearly a year, and I have heard nothing.

My failure to act at the time has tormented me for months. I have sought out more information about human trafficking, and the event I witnessed is what human trafficking looks like.


Maybe that girl was his daughter. Maybe she fell and cut her head. Maybe I was jumping to conclusions. But I am never again going to walk away from a girl who is clearly injured and potentially in trouble. I am going ask that girl if she’s OK, I am going to take a picture, and I am going to dial 911 immediately.

Don’t be a failure like me. Call 911. Take a picture. Take the risk, embarrass yourself or you will be tormented by your conscience as I am. We all must all step up, learn the signs of potential human trafficking, and stop allowing our young people to be fed to monsters.

The Centers for Disease Control and Prevention offers information and resources on human trafficking at www.cdc.gov/violenceprevention/sexualviolence/trafficking.html.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].

The word legacy has been synonymous with death to me. When so and so dies, we discuss their legacy. I had a powerful experience that changed my mind on this word that is befitting for this Legacies column.

Seven years ago, I was sitting in a room of powerful women and I was the youngest one there. I wasn’t sure how I got there, but I was glad I did because it changed my life. At the time, I was panicked. The exercise was called “Craft your legacy statement.”

But, this exercise was different. The ask was to “live into your legacy.” Craft a legacy statement in THREE minutes that summarizes what you want your legacy to be … and then decide the three things you need to do now to get there. So, here is my exact legacy 3-minute statement: I am an innovator pushing teaching hospitals to optimize training and patient care delivery through novel technologies and systems science. Clearly, I did not aim high enough. One of the other attendees stated her legacy simply as “Unleash the impossible!” So clearly, I was not able to think big at that moment, but I trudged on.

Next, I had to write the three things I was going to do to enact my legacy today. Things went from bad to worse quickly since I knew this was not going to be easy. The #1 thing had to be something I was going to stop doing because it did not fit with my legacy; #2 was what I was going to start doing to enact this legacy now; and, #3 was something I was going to do to get me closer to what I wanted to be doing. So, my #1, resign my current leadership role that I had had for 8 years; #2, start joining national committees that bridge education and quality; and #3, meet with senior leadership to pitch this new role as a bridging leader, aligning education and quality.

Like all conferences, I went home and forgot what I had done and learned. I settled back into my old life and routines. A few weeks later, a plain looking envelope with awful penmanship showed up at my doorstep addressed to me. It wasn’t until after I opened it and read what was inside that I realized I was the one with horrible penmanship! I completely forgot that I wrote this letter to myself even though they told me it would come and I would forget I wrote it! So, how did I do? Let’s just say if the letter did not arrive, I am not sure where I would be. Fortunately, it did come, and I followed my own orders. Fast forward to present day and I recently stepped into a new role – associate chief medical officer: clinical learning environment – a bridging leader who aligns education and clinical care missions for our health system. Let’s just say again, had that letter not arrived, I am not sure where I would be now.

 

I have been fortunate to do many things in hospital medicine – clinician, researcher, educator, and my latest role as a leader. Through it all, I would say that there are some lessons that I have picked up along the way that helped me advance, in ways I did not realize:

• Be bold. Years ago, when I was asked by my chair who they should pick to be chief resident, I thought “This must be a trick question – I should definitely tell him why I should be chosen – and then pick the next best person who I want to work with.” Apparently, I was the only person who did that, and that is why my chair chose me. Everyone else picked two other people. So the take-home point here is do not sell yourself short … ever.
• Look for the hidden gateways. A few years ago, I was asked if I wanted to be an institutional leader by the person who currently had that role. I was kind of thrown for a loop, since of course I would not want to appear like I wanted to take his job. I said everything was fine and I felt pretty good about my current positions. It was only a few weeks later that I realized that he was ascertaining my interest in his job since he was leaving. They gave the job to someone else and the word on the street was I was not interested. I totally missed the gate! While it wasn’t necessarily the job I missed out on, it was the opportunity to consider the job because I was afraid. So, don’t miss the gate. It’s the wormhole to a different life that may be the right one for you, but you need to “see it” to seize it.
• Work hard for the money and for the fun. There are many things Gwyneth Paltrow does that I do not agree with, but I will give her credit for one important lesson: she divides her movie roles into those she does for love (for example, The Royal Tenenbaums) and those she does for money (for example, Shallow Hal). It made me realize that even a Hollywood starlet has to do the stuff she may not want to do for the money. So, as a young person, you have to work hard for the money, but ideally it will help you take on a project you love, whatever it is. You’ve won the game when you’re mostly paid to work for the fun ... but that may take some time.
• Always optimize what is best for you personally AND professionally. While I was on maternity leave, the job of my dreams presented itself – or so I thought it did. It was at the intersection of policy, quality, and education, with a national stage, and I would not need to move. But, I knew I could not accept the travel commitment with a young child. While I wondered if I would have regrets, it turns out the right decision professionally also has to work personally. Likewise, there are professional obligations that I take on because it works personally.
• Figure out who your tea house pals are. A few years ago, I was in San Francisco with two close friends having an epic moment about what to do with our lives as adults. We were all on the cusp of changing our directions. Not surprisingly, we could see what the other needed to do, but we could not see it for ourselves. We still text each other sometimes about the need to go back to the Tea House. Sometimes your “tea house pals” are not necessarily those around you every day. They know you, but not everyone in your work place. This “arm’s length” or distance gives them the rational, unbiased perspective to advise you, that you or your colleagues will never have.
• Look for ways to enjoy the journey. Medicine is a very long road. I routinely think about this working with all the trainees and junior faculty I encounter. You can’t be in this solely for the end of the journey. The key is to find the joy in the journey. For me, that has always come from seeking out like-minded fellow travelers to share my highs and lows. While I tweet for many reasons, a big reason is that I take pleasure in watching others on the journey and also sharing my own journey.

Here’s to your journey and living your legacy!

Dr. Arora is associate chief medical officer, clinical learning environment, at University of Chicago Medicine, and assistant dean for scholarship and discovery at the University of Chicago Pritzker School of Medicine. You can follow her journey on Twitter.

The word legacy has been synonymous with death to me. When so and so dies, we discuss their legacy. I had a powerful experience that changed my mind on this word that is befitting for this Legacies column.

Seven years ago, I was sitting in a room of powerful women and I was the youngest one there. I wasn’t sure how I got there, but I was glad I did because it changed my life. At the time, I was panicked. The exercise was called “Craft your legacy statement.”

But, this exercise was different. The ask was to “live into your legacy.” Craft a legacy statement in THREE minutes that summarizes what you want your legacy to be … and then decide the three things you need to do now to get there. So, here is my exact legacy 3-minute statement: I am an innovator pushing teaching hospitals to optimize training and patient care delivery through novel technologies and systems science. Clearly, I did not aim high enough. One of the other attendees stated her legacy simply as “Unleash the impossible!” So clearly, I was not able to think big at that moment, but I trudged on.

Next, I had to write the three things I was going to do to enact my legacy today. Things went from bad to worse quickly since I knew this was not going to be easy. The #1 thing had to be something I was going to stop doing because it did not fit with my legacy; #2 was what I was going to start doing to enact this legacy now; and, #3 was something I was going to do to get me closer to what I wanted to be doing. So, my #1, resign my current leadership role that I had had for 8 years; #2, start joining national committees that bridge education and quality; and #3, meet with senior leadership to pitch this new role as a bridging leader, aligning education and quality.

Like all conferences, I went home and forgot what I had done and learned. I settled back into my old life and routines. A few weeks later, a plain looking envelope with awful penmanship showed up at my doorstep addressed to me. It wasn’t until after I opened it and read what was inside that I realized I was the one with horrible penmanship! I completely forgot that I wrote this letter to myself even though they told me it would come and I would forget I wrote it! So, how did I do? Let’s just say if the letter did not arrive, I am not sure where I would be. Fortunately, it did come, and I followed my own orders. Fast forward to present day and I recently stepped into a new role – associate chief medical officer: clinical learning environment – a bridging leader who aligns education and clinical care missions for our health system. Let’s just say again, had that letter not arrived, I am not sure where I would be now.

 

I have been fortunate to do many things in hospital medicine – clinician, researcher, educator, and my latest role as a leader. Through it all, I would say that there are some lessons that I have picked up along the way that helped me advance, in ways I did not realize:

• Be bold. Years ago, when I was asked by my chair who they should pick to be chief resident, I thought “This must be a trick question – I should definitely tell him why I should be chosen – and then pick the next best person who I want to work with.” Apparently, I was the only person who did that, and that is why my chair chose me. Everyone else picked two other people. So the take-home point here is do not sell yourself short … ever.
• Look for the hidden gateways. A few years ago, I was asked if I wanted to be an institutional leader by the person who currently had that role. I was kind of thrown for a loop, since of course I would not want to appear like I wanted to take his job. I said everything was fine and I felt pretty good about my current positions. It was only a few weeks later that I realized that he was ascertaining my interest in his job since he was leaving. They gave the job to someone else and the word on the street was I was not interested. I totally missed the gate! While it wasn’t necessarily the job I missed out on, it was the opportunity to consider the job because I was afraid. So, don’t miss the gate. It’s the wormhole to a different life that may be the right one for you, but you need to “see it” to seize it.
• Work hard for the money and for the fun. There are many things Gwyneth Paltrow does that I do not agree with, but I will give her credit for one important lesson: she divides her movie roles into those she does for love (for example, The Royal Tenenbaums) and those she does for money (for example, Shallow Hal). It made me realize that even a Hollywood starlet has to do the stuff she may not want to do for the money. So, as a young person, you have to work hard for the money, but ideally it will help you take on a project you love, whatever it is. You’ve won the game when you’re mostly paid to work for the fun ... but that may take some time.
• Always optimize what is best for you personally AND professionally. While I was on maternity leave, the job of my dreams presented itself – or so I thought it did. It was at the intersection of policy, quality, and education, with a national stage, and I would not need to move. But, I knew I could not accept the travel commitment with a young child. While I wondered if I would have regrets, it turns out the right decision professionally also has to work personally. Likewise, there are professional obligations that I take on because it works personally.
• Figure out who your tea house pals are. A few years ago, I was in San Francisco with two close friends having an epic moment about what to do with our lives as adults. We were all on the cusp of changing our directions. Not surprisingly, we could see what the other needed to do, but we could not see it for ourselves. We still text each other sometimes about the need to go back to the Tea House. Sometimes your “tea house pals” are not necessarily those around you every day. They know you, but not everyone in your work place. This “arm’s length” or distance gives them the rational, unbiased perspective to advise you, that you or your colleagues will never have.
• Look for ways to enjoy the journey. Medicine is a very long road. I routinely think about this working with all the trainees and junior faculty I encounter. You can’t be in this solely for the end of the journey. The key is to find the joy in the journey. For me, that has always come from seeking out like-minded fellow travelers to share my highs and lows. While I tweet for many reasons, a big reason is that I take pleasure in watching others on the journey and also sharing my own journey.

Here’s to your journey and living your legacy!

Dr. Arora is associate chief medical officer, clinical learning environment, at University of Chicago Medicine, and assistant dean for scholarship and discovery at the University of Chicago Pritzker School of Medicine. You can follow her journey on Twitter.

The word legacy has been synonymous with death to me. When so and so dies, we discuss their legacy. I had a powerful experience that changed my mind on this word that is befitting for this Legacies column.

Seven years ago, I was sitting in a room of powerful women and I was the youngest one there. I wasn’t sure how I got there, but I was glad I did because it changed my life. At the time, I was panicked. The exercise was called “Craft your legacy statement.”

But, this exercise was different. The ask was to “live into your legacy.” Craft a legacy statement in THREE minutes that summarizes what you want your legacy to be … and then decide the three things you need to do now to get there. So, here is my exact legacy 3-minute statement: I am an innovator pushing teaching hospitals to optimize training and patient care delivery through novel technologies and systems science. Clearly, I did not aim high enough. One of the other attendees stated her legacy simply as “Unleash the impossible!” So clearly, I was not able to think big at that moment, but I trudged on.

Next, I had to write the three things I was going to do to enact my legacy today. Things went from bad to worse quickly since I knew this was not going to be easy. The #1 thing had to be something I was going to stop doing because it did not fit with my legacy; #2 was what I was going to start doing to enact this legacy now; and, #3 was something I was going to do to get me closer to what I wanted to be doing. So, my #1, resign my current leadership role that I had had for 8 years; #2, start joining national committees that bridge education and quality; and #3, meet with senior leadership to pitch this new role as a bridging leader, aligning education and quality.

Like all conferences, I went home and forgot what I had done and learned. I settled back into my old life and routines. A few weeks later, a plain looking envelope with awful penmanship showed up at my doorstep addressed to me. It wasn’t until after I opened it and read what was inside that I realized I was the one with horrible penmanship! I completely forgot that I wrote this letter to myself even though they told me it would come and I would forget I wrote it! So, how did I do? Let’s just say if the letter did not arrive, I am not sure where I would be. Fortunately, it did come, and I followed my own orders. Fast forward to present day and I recently stepped into a new role – associate chief medical officer: clinical learning environment – a bridging leader who aligns education and clinical care missions for our health system. Let’s just say again, had that letter not arrived, I am not sure where I would be now.

 

I have been fortunate to do many things in hospital medicine – clinician, researcher, educator, and my latest role as a leader. Through it all, I would say that there are some lessons that I have picked up along the way that helped me advance, in ways I did not realize:

• Be bold. Years ago, when I was asked by my chair who they should pick to be chief resident, I thought “This must be a trick question – I should definitely tell him why I should be chosen – and then pick the next best person who I want to work with.” Apparently, I was the only person who did that, and that is why my chair chose me. Everyone else picked two other people. So the take-home point here is do not sell yourself short … ever.
• Look for the hidden gateways. A few years ago, I was asked if I wanted to be an institutional leader by the person who currently had that role. I was kind of thrown for a loop, since of course I would not want to appear like I wanted to take his job. I said everything was fine and I felt pretty good about my current positions. It was only a few weeks later that I realized that he was ascertaining my interest in his job since he was leaving. They gave the job to someone else and the word on the street was I was not interested. I totally missed the gate! While it wasn’t necessarily the job I missed out on, it was the opportunity to consider the job because I was afraid. So, don’t miss the gate. It’s the wormhole to a different life that may be the right one for you, but you need to “see it” to seize it.
• Work hard for the money and for the fun. There are many things Gwyneth Paltrow does that I do not agree with, but I will give her credit for one important lesson: she divides her movie roles into those she does for love (for example, The Royal Tenenbaums) and those she does for money (for example, Shallow Hal). It made me realize that even a Hollywood starlet has to do the stuff she may not want to do for the money. So, as a young person, you have to work hard for the money, but ideally it will help you take on a project you love, whatever it is. You’ve won the game when you’re mostly paid to work for the fun ... but that may take some time.
• Always optimize what is best for you personally AND professionally. While I was on maternity leave, the job of my dreams presented itself – or so I thought it did. It was at the intersection of policy, quality, and education, with a national stage, and I would not need to move. But, I knew I could not accept the travel commitment with a young child. While I wondered if I would have regrets, it turns out the right decision professionally also has to work personally. Likewise, there are professional obligations that I take on because it works personally.
• Figure out who your tea house pals are. A few years ago, I was in San Francisco with two close friends having an epic moment about what to do with our lives as adults. We were all on the cusp of changing our directions. Not surprisingly, we could see what the other needed to do, but we could not see it for ourselves. We still text each other sometimes about the need to go back to the Tea House. Sometimes your “tea house pals” are not necessarily those around you every day. They know you, but not everyone in your work place. This “arm’s length” or distance gives them the rational, unbiased perspective to advise you, that you or your colleagues will never have.
• Look for ways to enjoy the journey. Medicine is a very long road. I routinely think about this working with all the trainees and junior faculty I encounter. You can’t be in this solely for the end of the journey. The key is to find the joy in the journey. For me, that has always come from seeking out like-minded fellow travelers to share my highs and lows. While I tweet for many reasons, a big reason is that I take pleasure in watching others on the journey and also sharing my own journey.

Here’s to your journey and living your legacy!

Dr. Arora is associate chief medical officer, clinical learning environment, at University of Chicago Medicine, and assistant dean for scholarship and discovery at the University of Chicago Pritzker School of Medicine. You can follow her journey on Twitter.

In this edition of “How I will treat my next patient,” I take a look at two recent trials – one summarizes a presentation at the European Lung Cancer Congress on the value of durvalumab as adjuvant treatment in patients with locally-advanced non–small cell lung cancer and the other confirms the safety and efficacy of subcutaneously-administered trastuzumab as neoadjuvant treatment in HER2/-positive breast cancer patients.

PACIFIC trial

In the PACIFIC trial, 713 patients with unresectable, stage III non–small cell lung cancer (NSCLC) who received concurrent chemoradiation were randomized to receive adjuvant durvalumab or an identical placebo, for a year after radiation ended. The results were dramatic in favor of durvalumab (N Engl J Med. 2018;379:2342-50).

Durvalumab showed 24-month overall survival of 66.3% versus 55.6% with placebo (hazard ratio, 0.68, P = .0025) and progression-free survival of 17.2 months versus 5. 6 months (HR, 0.51). As expected, there were more grade 3-4 toxicities and treatment discontinuations with durvalumab than with placebo, but the toxicity seemed modest, given the substantial improvements in tumor-related outcomes.

At the recent European Lung Cancer Congress, Marina Garassino, MD, reported on Patient-Reported Outcomes (PRO) in PACIFIC. PROs were analyzed by PD-L1 level. A total of 63% of patients had PD-L1 tumor expression data for analysis. Overall, there were no major differences in PROs by PD-L1. Global quality of life did not differ by PD-L1 expression cohort.



These data support adjuvant durvalumab for stage III, chemoradiation-treated NSCLC patients, not only from efficacy and toxicity viewpoints, but also from the standpoint of the patient experience, independent of PD-L1 tumor expression.
 

What this means in practice

From every relevant perspective, regardless of histology and molecular features associated with their particular tumor, it is worthwhile for us to recommend – and for our patients to receive – durvalumab adjuvant therapy for up to 1 year after radiation ends, with close follow-up and adherence to the criteria for treatment modification or discontinuation as performed in the PACIFIC trial. These new data remove any lingering concerns about the value of this life-prolonging treatment.

Subcutaneous vs. IV trastuzumab

In this international phase 3 trial in early breast cancer patients, neoadjuvant chemotherapy was paired with either standard IV trastuzumab or subcutaneous trastuzumab at intervals of every 3 weeks. After the cytotoxic chemotherapy concluded, patients completed a 12-month course of trastuzumab with either the IV or subcutaneous administration, as previously randomized. The 6-year event-free survival and overall survival were 65% and 84%, respectively, for both the IV and subcutaneous treatment administration.

The authors concluded that these results are relevant to patients with low-risk HER2-positive breast cancer patients, for whom T-DM1 is not needed (JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339).

What this means in practice

These long-term data from the HannaH trial show persuasively that patients should be offered the more convenient, hopefully cheaper, subcutaneous route of administration. Since relapses beyond year 6 are unlikely, these data are unlikely to change with further follow-up. At our hospital, we recently made the decision to add subcutaneous trastuzumab to our formulary.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two recent trials – one summarizes a presentation at the European Lung Cancer Congress on the value of durvalumab as adjuvant treatment in patients with locally-advanced non–small cell lung cancer and the other confirms the safety and efficacy of subcutaneously-administered trastuzumab as neoadjuvant treatment in HER2/-positive breast cancer patients.

PACIFIC trial

In the PACIFIC trial, 713 patients with unresectable, stage III non–small cell lung cancer (NSCLC) who received concurrent chemoradiation were randomized to receive adjuvant durvalumab or an identical placebo, for a year after radiation ended. The results were dramatic in favor of durvalumab (N Engl J Med. 2018;379:2342-50).

Durvalumab showed 24-month overall survival of 66.3% versus 55.6% with placebo (hazard ratio, 0.68, P = .0025) and progression-free survival of 17.2 months versus 5. 6 months (HR, 0.51). As expected, there were more grade 3-4 toxicities and treatment discontinuations with durvalumab than with placebo, but the toxicity seemed modest, given the substantial improvements in tumor-related outcomes.

At the recent European Lung Cancer Congress, Marina Garassino, MD, reported on Patient-Reported Outcomes (PRO) in PACIFIC. PROs were analyzed by PD-L1 level. A total of 63% of patients had PD-L1 tumor expression data for analysis. Overall, there were no major differences in PROs by PD-L1. Global quality of life did not differ by PD-L1 expression cohort.



These data support adjuvant durvalumab for stage III, chemoradiation-treated NSCLC patients, not only from efficacy and toxicity viewpoints, but also from the standpoint of the patient experience, independent of PD-L1 tumor expression.
 

What this means in practice

From every relevant perspective, regardless of histology and molecular features associated with their particular tumor, it is worthwhile for us to recommend – and for our patients to receive – durvalumab adjuvant therapy for up to 1 year after radiation ends, with close follow-up and adherence to the criteria for treatment modification or discontinuation as performed in the PACIFIC trial. These new data remove any lingering concerns about the value of this life-prolonging treatment.

Subcutaneous vs. IV trastuzumab

In this international phase 3 trial in early breast cancer patients, neoadjuvant chemotherapy was paired with either standard IV trastuzumab or subcutaneous trastuzumab at intervals of every 3 weeks. After the cytotoxic chemotherapy concluded, patients completed a 12-month course of trastuzumab with either the IV or subcutaneous administration, as previously randomized. The 6-year event-free survival and overall survival were 65% and 84%, respectively, for both the IV and subcutaneous treatment administration.

The authors concluded that these results are relevant to patients with low-risk HER2-positive breast cancer patients, for whom T-DM1 is not needed (JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339).

What this means in practice

These long-term data from the HannaH trial show persuasively that patients should be offered the more convenient, hopefully cheaper, subcutaneous route of administration. Since relapses beyond year 6 are unlikely, these data are unlikely to change with further follow-up. At our hospital, we recently made the decision to add subcutaneous trastuzumab to our formulary.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I will treat my next patient,” I take a look at two recent trials – one summarizes a presentation at the European Lung Cancer Congress on the value of durvalumab as adjuvant treatment in patients with locally-advanced non–small cell lung cancer and the other confirms the safety and efficacy of subcutaneously-administered trastuzumab as neoadjuvant treatment in HER2/-positive breast cancer patients.

PACIFIC trial

In the PACIFIC trial, 713 patients with unresectable, stage III non–small cell lung cancer (NSCLC) who received concurrent chemoradiation were randomized to receive adjuvant durvalumab or an identical placebo, for a year after radiation ended. The results were dramatic in favor of durvalumab (N Engl J Med. 2018;379:2342-50).

Durvalumab showed 24-month overall survival of 66.3% versus 55.6% with placebo (hazard ratio, 0.68, P = .0025) and progression-free survival of 17.2 months versus 5. 6 months (HR, 0.51). As expected, there were more grade 3-4 toxicities and treatment discontinuations with durvalumab than with placebo, but the toxicity seemed modest, given the substantial improvements in tumor-related outcomes.

At the recent European Lung Cancer Congress, Marina Garassino, MD, reported on Patient-Reported Outcomes (PRO) in PACIFIC. PROs were analyzed by PD-L1 level. A total of 63% of patients had PD-L1 tumor expression data for analysis. Overall, there were no major differences in PROs by PD-L1. Global quality of life did not differ by PD-L1 expression cohort.



These data support adjuvant durvalumab for stage III, chemoradiation-treated NSCLC patients, not only from efficacy and toxicity viewpoints, but also from the standpoint of the patient experience, independent of PD-L1 tumor expression.
 

What this means in practice

From every relevant perspective, regardless of histology and molecular features associated with their particular tumor, it is worthwhile for us to recommend – and for our patients to receive – durvalumab adjuvant therapy for up to 1 year after radiation ends, with close follow-up and adherence to the criteria for treatment modification or discontinuation as performed in the PACIFIC trial. These new data remove any lingering concerns about the value of this life-prolonging treatment.

Subcutaneous vs. IV trastuzumab

In this international phase 3 trial in early breast cancer patients, neoadjuvant chemotherapy was paired with either standard IV trastuzumab or subcutaneous trastuzumab at intervals of every 3 weeks. After the cytotoxic chemotherapy concluded, patients completed a 12-month course of trastuzumab with either the IV or subcutaneous administration, as previously randomized. The 6-year event-free survival and overall survival were 65% and 84%, respectively, for both the IV and subcutaneous treatment administration.

The authors concluded that these results are relevant to patients with low-risk HER2-positive breast cancer patients, for whom T-DM1 is not needed (JAMA Oncol. 2019 Apr 18. doi: 10.1001/jamaoncol.2019.0339).

What this means in practice

These long-term data from the HannaH trial show persuasively that patients should be offered the more convenient, hopefully cheaper, subcutaneous route of administration. Since relapses beyond year 6 are unlikely, these data are unlikely to change with further follow-up. At our hospital, we recently made the decision to add subcutaneous trastuzumab to our formulary.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers, and in expanding access to clinical trials to medically underserved populations.

It’s late on a Thursday afternoon. Even through the six walls that separate you from the waiting room you can feel the impatient throng of families as you struggle to see the tympanic membrane of a feverish and uncooperative 3-year-old. You already have scraped his auditory canal once with your curette. Your gut tells you that he must have an otitis but deeper in your soul there are other voices reminding you that to make the diagnosis you must visualize his ear drum. Your skill and the technology on hand has failed you.

Getty Images

It’s a Sunday morning, weekend hours, and you are seeing a 12-year-old with a sore throat and fever. Her physical exam suggests that she has strep pharyngitis but the team member in charge of restocking supplies has forgotten to reorder rapid strep kits and you used the last one yesterday afternoon.

Do you ignore your training and treat these sick children with antibiotics?

If you are someone who perceives the world in black and white, your response to these scenarios is simple because you NEVER prescribe antibiotics without seeing a tympanic membrane or confirming your suspicion with a rapid strep test. There are unrealistic solutions that could include requesting an immediate ear/nose/throat consult or sending the patient on an hour-long odyssey to the hospital lab. But for the rest of us who see in shades of gray, we may have to compromise our principles and temporarily become poor antibiotic stewards. The question is, how often do you compromise? Once a week, once a month, twice a year, or twice a day?

A study published in Pediatrics looks at the issue of antibiotic stewardship as it relates to telemedicine (“Antibiotic Prescribing During Pediatrics Direct-to-Consumer Telemedicine Visits,” Pediatrics. 2019 May. doi: 10.1542/peds.2018-2491).

The investigators found that children with acute respiratory infections were more likely to receive antibiotics and less likely to receive guideline concordant management at direct-to-consumer (DTC) telemedicine visits than when they were seen by their primary care physician or at an urgent care center.

In their discussion, the researchers note several possible explanations for the discrepancies they observed. DTC telemedicine visits are limited by the devices used by the families and physicians and generally lack availability of otoscopy and strep testing. The authors also wonder whether “there may be differential expectations for antibiotics among children and parents who use DTC telemedicine versus in person care.” Does this mean that families who utilize DTC telemedicine undervalue in-person care and/or are willing to compromise by accepting what they may suspect is substandard care for the convenience of DTC telemedicine?

Which brings me to my point. A physician who accepts the challenge of seeing pediatric patients with acute respiratory illnesses knowing that he or she will not be able to visualize tympanic membranes or perform strep testing also has accepted the fact that he or she will be compromising the principles of antibiotic stewardship he or she must have – or maybe should have – learned in medical school or residency.

We all occasionally compromise our principles when technology fails us or when the situations are extraordinary. But I am troubled that there some physicians who are willing to practice in an environment in which they are aware that they will be compromising their antibiotic stewardship on a daily or even hourly basis.
 

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.” Email him at [email protected].

It’s late on a Thursday afternoon. Even through the six walls that separate you from the waiting room you can feel the impatient throng of families as you struggle to see the tympanic membrane of a feverish and uncooperative 3-year-old. You already have scraped his auditory canal once with your curette. Your gut tells you that he must have an otitis but deeper in your soul there are other voices reminding you that to make the diagnosis you must visualize his ear drum. Your skill and the technology on hand has failed you.

Getty Images

It’s a Sunday morning, weekend hours, and you are seeing a 12-year-old with a sore throat and fever. Her physical exam suggests that she has strep pharyngitis but the team member in charge of restocking supplies has forgotten to reorder rapid strep kits and you used the last one yesterday afternoon.

Do you ignore your training and treat these sick children with antibiotics?

If you are someone who perceives the world in black and white, your response to these scenarios is simple because you NEVER prescribe antibiotics without seeing a tympanic membrane or confirming your suspicion with a rapid strep test. There are unrealistic solutions that could include requesting an immediate ear/nose/throat consult or sending the patient on an hour-long odyssey to the hospital lab. But for the rest of us who see in shades of gray, we may have to compromise our principles and temporarily become poor antibiotic stewards. The question is, how often do you compromise? Once a week, once a month, twice a year, or twice a day?

A study published in Pediatrics looks at the issue of antibiotic stewardship as it relates to telemedicine (“Antibiotic Prescribing During Pediatrics Direct-to-Consumer Telemedicine Visits,” Pediatrics. 2019 May. doi: 10.1542/peds.2018-2491).

The investigators found that children with acute respiratory infections were more likely to receive antibiotics and less likely to receive guideline concordant management at direct-to-consumer (DTC) telemedicine visits than when they were seen by their primary care physician or at an urgent care center.

In their discussion, the researchers note several possible explanations for the discrepancies they observed. DTC telemedicine visits are limited by the devices used by the families and physicians and generally lack availability of otoscopy and strep testing. The authors also wonder whether “there may be differential expectations for antibiotics among children and parents who use DTC telemedicine versus in person care.” Does this mean that families who utilize DTC telemedicine undervalue in-person care and/or are willing to compromise by accepting what they may suspect is substandard care for the convenience of DTC telemedicine?

Which brings me to my point. A physician who accepts the challenge of seeing pediatric patients with acute respiratory illnesses knowing that he or she will not be able to visualize tympanic membranes or perform strep testing also has accepted the fact that he or she will be compromising the principles of antibiotic stewardship he or she must have – or maybe should have – learned in medical school or residency.

We all occasionally compromise our principles when technology fails us or when the situations are extraordinary. But I am troubled that there some physicians who are willing to practice in an environment in which they are aware that they will be compromising their antibiotic stewardship on a daily or even hourly basis.
 

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.” Email him at [email protected].

It’s late on a Thursday afternoon. Even through the six walls that separate you from the waiting room you can feel the impatient throng of families as you struggle to see the tympanic membrane of a feverish and uncooperative 3-year-old. You already have scraped his auditory canal once with your curette. Your gut tells you that he must have an otitis but deeper in your soul there are other voices reminding you that to make the diagnosis you must visualize his ear drum. Your skill and the technology on hand has failed you.

Getty Images

It’s a Sunday morning, weekend hours, and you are seeing a 12-year-old with a sore throat and fever. Her physical exam suggests that she has strep pharyngitis but the team member in charge of restocking supplies has forgotten to reorder rapid strep kits and you used the last one yesterday afternoon.

Do you ignore your training and treat these sick children with antibiotics?

If you are someone who perceives the world in black and white, your response to these scenarios is simple because you NEVER prescribe antibiotics without seeing a tympanic membrane or confirming your suspicion with a rapid strep test. There are unrealistic solutions that could include requesting an immediate ear/nose/throat consult or sending the patient on an hour-long odyssey to the hospital lab. But for the rest of us who see in shades of gray, we may have to compromise our principles and temporarily become poor antibiotic stewards. The question is, how often do you compromise? Once a week, once a month, twice a year, or twice a day?

A study published in Pediatrics looks at the issue of antibiotic stewardship as it relates to telemedicine (“Antibiotic Prescribing During Pediatrics Direct-to-Consumer Telemedicine Visits,” Pediatrics. 2019 May. doi: 10.1542/peds.2018-2491).

The investigators found that children with acute respiratory infections were more likely to receive antibiotics and less likely to receive guideline concordant management at direct-to-consumer (DTC) telemedicine visits than when they were seen by their primary care physician or at an urgent care center.

In their discussion, the researchers note several possible explanations for the discrepancies they observed. DTC telemedicine visits are limited by the devices used by the families and physicians and generally lack availability of otoscopy and strep testing. The authors also wonder whether “there may be differential expectations for antibiotics among children and parents who use DTC telemedicine versus in person care.” Does this mean that families who utilize DTC telemedicine undervalue in-person care and/or are willing to compromise by accepting what they may suspect is substandard care for the convenience of DTC telemedicine?

Which brings me to my point. A physician who accepts the challenge of seeing pediatric patients with acute respiratory illnesses knowing that he or she will not be able to visualize tympanic membranes or perform strep testing also has accepted the fact that he or she will be compromising the principles of antibiotic stewardship he or she must have – or maybe should have – learned in medical school or residency.

We all occasionally compromise our principles when technology fails us or when the situations are extraordinary. But I am troubled that there some physicians who are willing to practice in an environment in which they are aware that they will be compromising their antibiotic stewardship on a daily or even hourly basis.
 

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.” Email him at [email protected].

 

The diagnosis was straightforward. My patient’s reaction was not.

One Saturday evening, I receive a call from the emergency room about a man with a very high white blood cell count. For the past 7 years, he had chronic myeloid leukemia – a cancer, but one of the few that can be well controlled for years. The discovery of the medications that can do it revolutionized care for the disease.

For the last 7 years, Mr. C didn’t take that medication regularly. He was young, with no other medical problems, and this was the only medication he was supposed to take. But his use was sporadic at best.

What was it, I wondered? Cost? Side effects? Not understanding the seriousness of having leukemia? No, the medication was fully covered by his insurance. No, he tolerated it well. Instead, his on-and-off medication schedule came across as a strange sense of apathy. He didn’t seem to recognize his agency in his own life.

Now, not only is his white count extremely high, but the majority are the cancerous cells. I look at his blood under the microscope – blasts everywhere. He has progressed from a chronic, indolent disease that can be kept at bay into the dreaded blast crisis, which is essentially an acute leukemia but even more challenging to treat.

It is very serious. I tell him this. “I am worried your leukemia has progressed into what we call a blast crisis,” I say. “Has anyone ever talked to you about this before?”

“Hmm, I think Dr. M may have said something,” he says. His medical chart over the last 7 years was populated with notes from his hematologist documenting their discussions of this possibility.

“This is serious,” I continue. “You will need to come into the hospital and we need to start medication to lower your white count. Otherwise you could have a stroke.”

“Okay.”

“As the white count comes down, your cells will break open and the chemicals in them can make you very sick. So we will have to check your blood often to watch for this.”

“Got it.”

“And we will change your chemotherapy pill.” I pause, letting it sink in, then repeat for emphasis: “This is very serious.”

“Sure thing, Doc.”

“I know I’ve said a lot. What are your thoughts?”

He looks at his wife, then back at me. He seems unfazed. Just as unfazed as when his hematologist warned this could happen. Just as unfazed as the day he learned his diagnosis.

He smiles and shrugs. “What will be, will be.”

As I listened to him, I honestly couldn’t tell if this was the best coping mechanism I had ever seen or the worst.

On one hand, his apathy had hurt him, clearly and indisputably. Refusing to acknowledge his agency in his medical outcomes allowed him to be cavalier about taking the cure. The cure was in a bottle on his kitchen shelf, an arm’s reach away, and he chose to reach elsewhere.

On the other hand, it was unusual to see someone so at peace with being so critically ill. His acceptance of his new reality was refreshing. There were no heartbreaking questions about whether this was his fault. There was no agonizing over what could have been. His apathy gave him closure and his loved ones comfort.

I’ve written before about how a cancer diagnosis involves holding two seemingly competing ideas in one’s mind at once. Last month, I wrote about how it is possible to be realistic about a grim prognosis while retaining hope that a treatment may work. I discussed that realism and hopefulness are compatible beliefs, and it’s okay – preferred, even – to hold them at once.

Mr. C’s strange sense of apathy made me think about another mental limbo, this one involving control. As doctors and patients, we like when we have agency over outcomes. Take these medications, and you will be okay. Undergo this procedure, and you will reduce your risk of recurrence. At the same time, poor outcomes still occur when everything is done “right.” When that happens, it can be psychologically beneficial to relinquish control. Doing so discards the unhelpful emotions of guilt and blame in favor of acceptance.

Mr. C’s apathy seemed to be present from day 1. But now, in a dire blast crisis, what was once a harmful attitude actually became a helpful one.

His “what will be, will be” attitude wasn’t inherently maladaptive; it was ill timed. Under the right circumstances, well-placed apathy can be leveraged as a positive coping mechanism.

But alas, if only there were a switch to turn on the right emotion at the right time. There’s no right or wrong or sensible reaction to cancer. There’s only a swirl of messy, overwhelming feelings. It’s trying to bring effective emotions to light at the right time while playing whack-a-mole with the others. It’s cognitive dissonance. It’s exhausting. Cancer doesn’t create personalities; it surfaces them.

It’s the last day of Mr. C’s hospitalization. His blast crisis is amazingly under good control.

“So,” I say. “Will you take your medications now?”

“Sure,” he says instinctively. I look at him. “I mean, honestly, Doc? I’m not sure.”

As we shake hands, I wonder if I’ll ever truly understand Mr. C’s motivations. But I can’t wonder too long. I can only control my part: I hand him his medications and wish him luck.

Minor details of this story were changed to protect privacy.
 

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

 

The diagnosis was straightforward. My patient’s reaction was not.

One Saturday evening, I receive a call from the emergency room about a man with a very high white blood cell count. For the past 7 years, he had chronic myeloid leukemia – a cancer, but one of the few that can be well controlled for years. The discovery of the medications that can do it revolutionized care for the disease.

For the last 7 years, Mr. C didn’t take that medication regularly. He was young, with no other medical problems, and this was the only medication he was supposed to take. But his use was sporadic at best.

What was it, I wondered? Cost? Side effects? Not understanding the seriousness of having leukemia? No, the medication was fully covered by his insurance. No, he tolerated it well. Instead, his on-and-off medication schedule came across as a strange sense of apathy. He didn’t seem to recognize his agency in his own life.

Now, not only is his white count extremely high, but the majority are the cancerous cells. I look at his blood under the microscope – blasts everywhere. He has progressed from a chronic, indolent disease that can be kept at bay into the dreaded blast crisis, which is essentially an acute leukemia but even more challenging to treat.

It is very serious. I tell him this. “I am worried your leukemia has progressed into what we call a blast crisis,” I say. “Has anyone ever talked to you about this before?”

“Hmm, I think Dr. M may have said something,” he says. His medical chart over the last 7 years was populated with notes from his hematologist documenting their discussions of this possibility.

“This is serious,” I continue. “You will need to come into the hospital and we need to start medication to lower your white count. Otherwise you could have a stroke.”

“Okay.”

“As the white count comes down, your cells will break open and the chemicals in them can make you very sick. So we will have to check your blood often to watch for this.”

“Got it.”

“And we will change your chemotherapy pill.” I pause, letting it sink in, then repeat for emphasis: “This is very serious.”

“Sure thing, Doc.”

“I know I’ve said a lot. What are your thoughts?”

He looks at his wife, then back at me. He seems unfazed. Just as unfazed as when his hematologist warned this could happen. Just as unfazed as the day he learned his diagnosis.

He smiles and shrugs. “What will be, will be.”

As I listened to him, I honestly couldn’t tell if this was the best coping mechanism I had ever seen or the worst.

On one hand, his apathy had hurt him, clearly and indisputably. Refusing to acknowledge his agency in his medical outcomes allowed him to be cavalier about taking the cure. The cure was in a bottle on his kitchen shelf, an arm’s reach away, and he chose to reach elsewhere.

On the other hand, it was unusual to see someone so at peace with being so critically ill. His acceptance of his new reality was refreshing. There were no heartbreaking questions about whether this was his fault. There was no agonizing over what could have been. His apathy gave him closure and his loved ones comfort.

I’ve written before about how a cancer diagnosis involves holding two seemingly competing ideas in one’s mind at once. Last month, I wrote about how it is possible to be realistic about a grim prognosis while retaining hope that a treatment may work. I discussed that realism and hopefulness are compatible beliefs, and it’s okay – preferred, even – to hold them at once.

Mr. C’s strange sense of apathy made me think about another mental limbo, this one involving control. As doctors and patients, we like when we have agency over outcomes. Take these medications, and you will be okay. Undergo this procedure, and you will reduce your risk of recurrence. At the same time, poor outcomes still occur when everything is done “right.” When that happens, it can be psychologically beneficial to relinquish control. Doing so discards the unhelpful emotions of guilt and blame in favor of acceptance.

Mr. C’s apathy seemed to be present from day 1. But now, in a dire blast crisis, what was once a harmful attitude actually became a helpful one.

His “what will be, will be” attitude wasn’t inherently maladaptive; it was ill timed. Under the right circumstances, well-placed apathy can be leveraged as a positive coping mechanism.

But alas, if only there were a switch to turn on the right emotion at the right time. There’s no right or wrong or sensible reaction to cancer. There’s only a swirl of messy, overwhelming feelings. It’s trying to bring effective emotions to light at the right time while playing whack-a-mole with the others. It’s cognitive dissonance. It’s exhausting. Cancer doesn’t create personalities; it surfaces them.

It’s the last day of Mr. C’s hospitalization. His blast crisis is amazingly under good control.

“So,” I say. “Will you take your medications now?”

“Sure,” he says instinctively. I look at him. “I mean, honestly, Doc? I’m not sure.”

As we shake hands, I wonder if I’ll ever truly understand Mr. C’s motivations. But I can’t wonder too long. I can only control my part: I hand him his medications and wish him luck.

Minor details of this story were changed to protect privacy.
 

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

 

The diagnosis was straightforward. My patient’s reaction was not.

One Saturday evening, I receive a call from the emergency room about a man with a very high white blood cell count. For the past 7 years, he had chronic myeloid leukemia – a cancer, but one of the few that can be well controlled for years. The discovery of the medications that can do it revolutionized care for the disease.

For the last 7 years, Mr. C didn’t take that medication regularly. He was young, with no other medical problems, and this was the only medication he was supposed to take. But his use was sporadic at best.

What was it, I wondered? Cost? Side effects? Not understanding the seriousness of having leukemia? No, the medication was fully covered by his insurance. No, he tolerated it well. Instead, his on-and-off medication schedule came across as a strange sense of apathy. He didn’t seem to recognize his agency in his own life.

Now, not only is his white count extremely high, but the majority are the cancerous cells. I look at his blood under the microscope – blasts everywhere. He has progressed from a chronic, indolent disease that can be kept at bay into the dreaded blast crisis, which is essentially an acute leukemia but even more challenging to treat.

It is very serious. I tell him this. “I am worried your leukemia has progressed into what we call a blast crisis,” I say. “Has anyone ever talked to you about this before?”

“Hmm, I think Dr. M may have said something,” he says. His medical chart over the last 7 years was populated with notes from his hematologist documenting their discussions of this possibility.

“This is serious,” I continue. “You will need to come into the hospital and we need to start medication to lower your white count. Otherwise you could have a stroke.”

“Okay.”

“As the white count comes down, your cells will break open and the chemicals in them can make you very sick. So we will have to check your blood often to watch for this.”

“Got it.”

“And we will change your chemotherapy pill.” I pause, letting it sink in, then repeat for emphasis: “This is very serious.”

“Sure thing, Doc.”

“I know I’ve said a lot. What are your thoughts?”

He looks at his wife, then back at me. He seems unfazed. Just as unfazed as when his hematologist warned this could happen. Just as unfazed as the day he learned his diagnosis.

He smiles and shrugs. “What will be, will be.”

As I listened to him, I honestly couldn’t tell if this was the best coping mechanism I had ever seen or the worst.

On one hand, his apathy had hurt him, clearly and indisputably. Refusing to acknowledge his agency in his medical outcomes allowed him to be cavalier about taking the cure. The cure was in a bottle on his kitchen shelf, an arm’s reach away, and he chose to reach elsewhere.

On the other hand, it was unusual to see someone so at peace with being so critically ill. His acceptance of his new reality was refreshing. There were no heartbreaking questions about whether this was his fault. There was no agonizing over what could have been. His apathy gave him closure and his loved ones comfort.

I’ve written before about how a cancer diagnosis involves holding two seemingly competing ideas in one’s mind at once. Last month, I wrote about how it is possible to be realistic about a grim prognosis while retaining hope that a treatment may work. I discussed that realism and hopefulness are compatible beliefs, and it’s okay – preferred, even – to hold them at once.

Mr. C’s strange sense of apathy made me think about another mental limbo, this one involving control. As doctors and patients, we like when we have agency over outcomes. Take these medications, and you will be okay. Undergo this procedure, and you will reduce your risk of recurrence. At the same time, poor outcomes still occur when everything is done “right.” When that happens, it can be psychologically beneficial to relinquish control. Doing so discards the unhelpful emotions of guilt and blame in favor of acceptance.

Mr. C’s apathy seemed to be present from day 1. But now, in a dire blast crisis, what was once a harmful attitude actually became a helpful one.

His “what will be, will be” attitude wasn’t inherently maladaptive; it was ill timed. Under the right circumstances, well-placed apathy can be leveraged as a positive coping mechanism.

But alas, if only there were a switch to turn on the right emotion at the right time. There’s no right or wrong or sensible reaction to cancer. There’s only a swirl of messy, overwhelming feelings. It’s trying to bring effective emotions to light at the right time while playing whack-a-mole with the others. It’s cognitive dissonance. It’s exhausting. Cancer doesn’t create personalities; it surfaces them.

It’s the last day of Mr. C’s hospitalization. His blast crisis is amazingly under good control.

“So,” I say. “Will you take your medications now?”

“Sure,” he says instinctively. I look at him. “I mean, honestly, Doc? I’m not sure.”

As we shake hands, I wonder if I’ll ever truly understand Mr. C’s motivations. But I can’t wonder too long. I can only control my part: I hand him his medications and wish him luck.

Minor details of this story were changed to protect privacy.
 

Dr. Yurkiewicz is a fellow in hematology and oncology at Stanford (Calif.) University. Follow her on Twitter @ilanayurkiewicz.

 

The recent publication of the changes and current levels of evidence for the guidelines from the American College of Cardiology, American Heart Association, and the European Society of Cardiology once again indicates that the level of high-quality scientific data supporting the decision making process is limited.

Of the thousands of recommendations among the guidelines provided, level A data – which is supported by at least two randomized, controlled trials (RCT), arguably the gold standard for the proof of benefit of a treatment program – was available in only 8.5% of ACC/AHA recommendations and in 14.2% of ESC recommendations. The recent review covering guidelines published from 2008 to 2018 has changed very little since the previous review carried out on data collected between 1999 and 2014 (JAMA. 2019 Mar 19;321[11]:1069-80). Admittedly, by the nature of their design, RCTs represent a very special subset of any disease process but they are the best we can do. The remainder of the guidelines is supported by nonrandomized data and consensus opinion of “experts.” The absence of randomized data in the rest of the guidelines creates an area of uncertainty between clinical practice and outcomes.

Guidelines have been with us for almost 30 years and have provided a near “cookbook recipe” for the treatment of almost the totality of cardiovascular care, both in the United States and Europe. There is little evidence that guideline dissemination results in a beneficial effect on cardiovascular care, instead reflecting the contemporary published research and informed opinion of our generation.

Despite the limitation of hard data based on RCTs, cardiovascular mortality has leveled off in the last few years. Although there are a number of areas that could be investigated with more focused and practical RCTs, there has been little enthusiasm by either the National Heart, Lung, and Blood Institute or the pharmaceutical or device industries to investigate existing cardiovascular drugs and/or devices to better elucidate nuanced therapy for subsets of heart disease that remain in the uncertain data areas. In fact, the current report shows that there has been little change in guidelines in the last 10 years. Most effort has been focused on new drug development and application.

Much of the advance in cardiovascular care and decrease in mortality is a result of the development of new drugs for the treatment of hypertension, management of hypercholesterolemia, and MI, together with coronary angiography and its interventional permutations of the previous 50 years. Those advances are now part of our knowledge base, our therapeutic DNA, and in the absence of some new scientific breakthrough, there is little to expect from future guideline development. Medical students and house officers are being taught as fact what we found as exciting new therapy just a few short years ago. Guidelines are now part of textbook knowledge and until new clinical outcome are reported, guidelines will probably serve a useful reference material but will not lead to much change in clinical care.

Even so, treating the patient in the clinic and in the hospital still requires the doctor to practice the “art” of medicine and to synthesize therapy based on the paucity of scientific data and quasi knowledge acquired over a generation.

The appreciation that much is unknown gives the doctor the humility required to be sensitive to patient needs and their symptoms and the aspiration for new, science-based data. This is still part of the excitement of being a doctor.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

 

The recent publication of the changes and current levels of evidence for the guidelines from the American College of Cardiology, American Heart Association, and the European Society of Cardiology once again indicates that the level of high-quality scientific data supporting the decision making process is limited.

Of the thousands of recommendations among the guidelines provided, level A data – which is supported by at least two randomized, controlled trials (RCT), arguably the gold standard for the proof of benefit of a treatment program – was available in only 8.5% of ACC/AHA recommendations and in 14.2% of ESC recommendations. The recent review covering guidelines published from 2008 to 2018 has changed very little since the previous review carried out on data collected between 1999 and 2014 (JAMA. 2019 Mar 19;321[11]:1069-80). Admittedly, by the nature of their design, RCTs represent a very special subset of any disease process but they are the best we can do. The remainder of the guidelines is supported by nonrandomized data and consensus opinion of “experts.” The absence of randomized data in the rest of the guidelines creates an area of uncertainty between clinical practice and outcomes.

Guidelines have been with us for almost 30 years and have provided a near “cookbook recipe” for the treatment of almost the totality of cardiovascular care, both in the United States and Europe. There is little evidence that guideline dissemination results in a beneficial effect on cardiovascular care, instead reflecting the contemporary published research and informed opinion of our generation.

Despite the limitation of hard data based on RCTs, cardiovascular mortality has leveled off in the last few years. Although there are a number of areas that could be investigated with more focused and practical RCTs, there has been little enthusiasm by either the National Heart, Lung, and Blood Institute or the pharmaceutical or device industries to investigate existing cardiovascular drugs and/or devices to better elucidate nuanced therapy for subsets of heart disease that remain in the uncertain data areas. In fact, the current report shows that there has been little change in guidelines in the last 10 years. Most effort has been focused on new drug development and application.

Much of the advance in cardiovascular care and decrease in mortality is a result of the development of new drugs for the treatment of hypertension, management of hypercholesterolemia, and MI, together with coronary angiography and its interventional permutations of the previous 50 years. Those advances are now part of our knowledge base, our therapeutic DNA, and in the absence of some new scientific breakthrough, there is little to expect from future guideline development. Medical students and house officers are being taught as fact what we found as exciting new therapy just a few short years ago. Guidelines are now part of textbook knowledge and until new clinical outcome are reported, guidelines will probably serve a useful reference material but will not lead to much change in clinical care.

Even so, treating the patient in the clinic and in the hospital still requires the doctor to practice the “art” of medicine and to synthesize therapy based on the paucity of scientific data and quasi knowledge acquired over a generation.

The appreciation that much is unknown gives the doctor the humility required to be sensitive to patient needs and their symptoms and the aspiration for new, science-based data. This is still part of the excitement of being a doctor.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

 

The recent publication of the changes and current levels of evidence for the guidelines from the American College of Cardiology, American Heart Association, and the European Society of Cardiology once again indicates that the level of high-quality scientific data supporting the decision making process is limited.

Of the thousands of recommendations among the guidelines provided, level A data – which is supported by at least two randomized, controlled trials (RCT), arguably the gold standard for the proof of benefit of a treatment program – was available in only 8.5% of ACC/AHA recommendations and in 14.2% of ESC recommendations. The recent review covering guidelines published from 2008 to 2018 has changed very little since the previous review carried out on data collected between 1999 and 2014 (JAMA. 2019 Mar 19;321[11]:1069-80). Admittedly, by the nature of their design, RCTs represent a very special subset of any disease process but they are the best we can do. The remainder of the guidelines is supported by nonrandomized data and consensus opinion of “experts.” The absence of randomized data in the rest of the guidelines creates an area of uncertainty between clinical practice and outcomes.

Guidelines have been with us for almost 30 years and have provided a near “cookbook recipe” for the treatment of almost the totality of cardiovascular care, both in the United States and Europe. There is little evidence that guideline dissemination results in a beneficial effect on cardiovascular care, instead reflecting the contemporary published research and informed opinion of our generation.

Despite the limitation of hard data based on RCTs, cardiovascular mortality has leveled off in the last few years. Although there are a number of areas that could be investigated with more focused and practical RCTs, there has been little enthusiasm by either the National Heart, Lung, and Blood Institute or the pharmaceutical or device industries to investigate existing cardiovascular drugs and/or devices to better elucidate nuanced therapy for subsets of heart disease that remain in the uncertain data areas. In fact, the current report shows that there has been little change in guidelines in the last 10 years. Most effort has been focused on new drug development and application.

Much of the advance in cardiovascular care and decrease in mortality is a result of the development of new drugs for the treatment of hypertension, management of hypercholesterolemia, and MI, together with coronary angiography and its interventional permutations of the previous 50 years. Those advances are now part of our knowledge base, our therapeutic DNA, and in the absence of some new scientific breakthrough, there is little to expect from future guideline development. Medical students and house officers are being taught as fact what we found as exciting new therapy just a few short years ago. Guidelines are now part of textbook knowledge and until new clinical outcome are reported, guidelines will probably serve a useful reference material but will not lead to much change in clinical care.

Even so, treating the patient in the clinic and in the hospital still requires the doctor to practice the “art” of medicine and to synthesize therapy based on the paucity of scientific data and quasi knowledge acquired over a generation.

The appreciation that much is unknown gives the doctor the humility required to be sensitive to patient needs and their symptoms and the aspiration for new, science-based data. This is still part of the excitement of being a doctor.

Dr. Goldstein, medical editor of Cardiology News, is professor of medicine at Wayne State University and division head emeritus of cardiovascular medicine at Henry Ford Hospital, both in Detroit. He is on data safety monitoring committees for the National Institutes of Health and several pharmaceutical companies.

 

Careful management of bipolar disorder during pregnancy is critical because for so many patients with this illness, the road to emotional well-being has been a long one, requiring a combination of careful pharmacologic and nonpharmacologic strategies.

KatarzynaBialasiewicz/thinkstockphotos

Half of referrals to our Center for Women’s Mental Health – where we evaluate and treat women before, during, and after pregnancy – are for women who have histories of bipolar disorder. My colleagues and I are asked at continuing medical education programs what we “always do” and “never do” with respect to the treatment of these patients.
 

What about discontinuation of mood stabilizers during pregnancy and risk of relapse?

We never abruptly stop mood stabilizers if a patient has an unplanned pregnancy – a common scenario, with 50% of pregnancies across the country being unplanned across sociodemographic lines – save for sodium valproate, which is a clearly a documented teratogen; it increases risk for organ malformation and behavioral difficulties in exposed offspring. In our center, we typically view the use of sodium valproate in reproductive age women as contraindicated.

One may then question the circumstances under which lithium might be used during pregnancy, because many clinicians are faced with patients who have been exquisite responders to lithium. Such a patient may present with a history of mania, but there are obvious concerns given the historical literature, and even some more recent reports, that describe an increased risk of teratogenicity with fetal exposure to lithium.

Maintenance pharmacotherapy for women with bipolar disorder during pregnancy is so important, not only to decrease the risk of relapse following discontinuation of mood stabilizers, but because recurrence of illness during pregnancy for these patients is a very strong predictor of risk for postpartum depression. Women with bipolar disorder already are at a fivefold increased risk for postpartum depression, so discussion of sustaining euthymia during pregnancy for bipolar women is particularly timely given the focus nationally on treatment and prevention of postpartum depression.
 

In patients with history of mania, what about stopping treatment with lithium and other effective treatments during pregnancy?

Historically, we sometimes divided patients with bipolar disorder into those with “more severe recurrent disease” compared with those with more distant, circumscribed disease. In patients with more remote histories of mood dysregulation, we tended to discontinue treatment with mood stabilizers such as lithium or even newer second-generation atypical antipsychotics to see if patients could at least get through earlier stages of pregnancy before going back on anti-manic treatment.

Our experience now over several decades has revealed that this can be a risky clinical move. What we see is that even in patients with histories of mania years in the past (i.e., a circumscribed episode of mania during college in a woman now 35 years old with intervening sustained well-being), discontinuation of treatment that got patients well can lead to recurrence. Hence, we should not confuse an exquisite response to treatment with long periods of well-being as suggesting that the patient has a less severe form of bipolar disorder and hence the capacity to sustain that well-being when treatment is removed.
 

 

What about increasing/decreasing lithium dose during pregnancy and around time of delivery?

Select patients may be sensitive to changes in plasma levels of lithium, but the literature suggests that the clinical utility of arbitrarily sustaining plasma levels at the upper limit of the accepted range may be of only modest advantage, if any. With this as a backdrop and even while knowing that increased plasma volume of pregnancy is associated with a fall in plasma level of most medications, we do not arbitrarily increase the dose of lithium across pregnancy merely to sustain a level in the absence of a change in clinical symptoms. Indeed, to my knowledge, currently available data supporting a clear correlation of decline in plasma levels and frank change in symptoms during pregnancy are very sparse, if existent.

Earlier work had suggested that lithium dosage should be reduced proximate to delivery, a period characterized by rapid shifts in plasma volume during the acute peripartum period. Because physicians in our center do not alter lithium dose across pregnancy, we never reduce the dose of lithium proximate to delivery because of a theoretical concern for increased risk of either neonatal toxicity or maternal lithium toxicity, which is essentially nonexistent in terms of systematic reports in the literature.

Obvious concerns about lithium during pregnancy have focused on increased risk of teratogenesis, with the earliest reports supporting an increased risk of Epstein’s anomaly (0.05%-0.1%). More recent reports suggest an increased risk of cardiovascular malformations, which according to some investigators may be dose dependent.

For those patients who are exquisitely responsive to lithium, we typically leave them on the medicine and avail ourselves of current fetal echocardiographic evaluation at 16 weeks to 18 weeks to document the integrity of the fetal cardiac anatomy. Although the risk for cardiac malformations associated with lithium exposure during the first trimester is still exceedingly small, it is still extremely reassuring to patients to know that they are safely on the other side of a teratogenic window.
 

What about lamotrigine levels across pregnancy?

The last decade has seen a dramatic decrease in the administration of lithium to women with bipolar disorder, and growing use of both lamotrigine and second-generation atypical antipsychotics (frequently in combination) as an alternative. The changes in plasma level of lamotrigine across pregnancy are being increasingly well documented based on rigorous studies (Obstet Gynecol Clin North Am. 2018 Sep;45[3]:403-17).

These are welcome data, but the correlation between plasma concentration of lamotrigine and clinical response is a poor one. To date, there are sparse data to suggest that maintaining plasma levels of lithium or lamotrigine at a certain level during pregnancy changes clinical outcome. Following lamotrigine plasma levels during pregnancy seems more like an academic exercise than a procedure associated with particular clinical value.

As in the case of lithium, we never change lamotrigine doses proximate to pregnancy because of the absence of reports of neonatal toxicity associated with using lamotrigine during the peripartum period. The rationale for removing or minimizing the use of an effective medicine proximate to delivery, a period of risk for bipolar women, is lacking.

In 2019, we clearly are seeing a growing use of atypical antipsychotics for the treatment of bipolar disorder during pregnancy frequently coadministered with medicines such as lamotrigine as opposed to lithium. The accumulated data to date on second-generation atypical antipsychotics are not definitive, but increasingly are reassuring in terms of absence of a clear signal for teratogenicity; hence, our comfort in using this class of medicines is only growing, which is important given the prevalence of use of these agents in reproductive-age women.

If there is a single critical guiding principle for the clinician when it comes to managing bipolar women during pregnancy and the postpartum period, it is sustaining euthymia. With the recent focus of the U.S. Preventive Services Task Force on prevention of postpartum depression, nothing is more helpful perhaps than keeping women with bipolar disorder well, both proximate to pregnancy and during an actual pregnancy. Keeping those patients well maximizes the likelihood that they will proceed across the peripartum and into the postpartum period with a level of emotional well-being that optimizes and maximizes positive long-term outcomes for both patients and families.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

 

Careful management of bipolar disorder during pregnancy is critical because for so many patients with this illness, the road to emotional well-being has been a long one, requiring a combination of careful pharmacologic and nonpharmacologic strategies.

KatarzynaBialasiewicz/thinkstockphotos

Half of referrals to our Center for Women’s Mental Health – where we evaluate and treat women before, during, and after pregnancy – are for women who have histories of bipolar disorder. My colleagues and I are asked at continuing medical education programs what we “always do” and “never do” with respect to the treatment of these patients.
 

What about discontinuation of mood stabilizers during pregnancy and risk of relapse?

We never abruptly stop mood stabilizers if a patient has an unplanned pregnancy – a common scenario, with 50% of pregnancies across the country being unplanned across sociodemographic lines – save for sodium valproate, which is a clearly a documented teratogen; it increases risk for organ malformation and behavioral difficulties in exposed offspring. In our center, we typically view the use of sodium valproate in reproductive age women as contraindicated.

One may then question the circumstances under which lithium might be used during pregnancy, because many clinicians are faced with patients who have been exquisite responders to lithium. Such a patient may present with a history of mania, but there are obvious concerns given the historical literature, and even some more recent reports, that describe an increased risk of teratogenicity with fetal exposure to lithium.

Maintenance pharmacotherapy for women with bipolar disorder during pregnancy is so important, not only to decrease the risk of relapse following discontinuation of mood stabilizers, but because recurrence of illness during pregnancy for these patients is a very strong predictor of risk for postpartum depression. Women with bipolar disorder already are at a fivefold increased risk for postpartum depression, so discussion of sustaining euthymia during pregnancy for bipolar women is particularly timely given the focus nationally on treatment and prevention of postpartum depression.
 

In patients with history of mania, what about stopping treatment with lithium and other effective treatments during pregnancy?

Historically, we sometimes divided patients with bipolar disorder into those with “more severe recurrent disease” compared with those with more distant, circumscribed disease. In patients with more remote histories of mood dysregulation, we tended to discontinue treatment with mood stabilizers such as lithium or even newer second-generation atypical antipsychotics to see if patients could at least get through earlier stages of pregnancy before going back on anti-manic treatment.

Our experience now over several decades has revealed that this can be a risky clinical move. What we see is that even in patients with histories of mania years in the past (i.e., a circumscribed episode of mania during college in a woman now 35 years old with intervening sustained well-being), discontinuation of treatment that got patients well can lead to recurrence. Hence, we should not confuse an exquisite response to treatment with long periods of well-being as suggesting that the patient has a less severe form of bipolar disorder and hence the capacity to sustain that well-being when treatment is removed.
 

 

What about increasing/decreasing lithium dose during pregnancy and around time of delivery?

Select patients may be sensitive to changes in plasma levels of lithium, but the literature suggests that the clinical utility of arbitrarily sustaining plasma levels at the upper limit of the accepted range may be of only modest advantage, if any. With this as a backdrop and even while knowing that increased plasma volume of pregnancy is associated with a fall in plasma level of most medications, we do not arbitrarily increase the dose of lithium across pregnancy merely to sustain a level in the absence of a change in clinical symptoms. Indeed, to my knowledge, currently available data supporting a clear correlation of decline in plasma levels and frank change in symptoms during pregnancy are very sparse, if existent.

Earlier work had suggested that lithium dosage should be reduced proximate to delivery, a period characterized by rapid shifts in plasma volume during the acute peripartum period. Because physicians in our center do not alter lithium dose across pregnancy, we never reduce the dose of lithium proximate to delivery because of a theoretical concern for increased risk of either neonatal toxicity or maternal lithium toxicity, which is essentially nonexistent in terms of systematic reports in the literature.

Obvious concerns about lithium during pregnancy have focused on increased risk of teratogenesis, with the earliest reports supporting an increased risk of Epstein’s anomaly (0.05%-0.1%). More recent reports suggest an increased risk of cardiovascular malformations, which according to some investigators may be dose dependent.

For those patients who are exquisitely responsive to lithium, we typically leave them on the medicine and avail ourselves of current fetal echocardiographic evaluation at 16 weeks to 18 weeks to document the integrity of the fetal cardiac anatomy. Although the risk for cardiac malformations associated with lithium exposure during the first trimester is still exceedingly small, it is still extremely reassuring to patients to know that they are safely on the other side of a teratogenic window.
 

What about lamotrigine levels across pregnancy?

The last decade has seen a dramatic decrease in the administration of lithium to women with bipolar disorder, and growing use of both lamotrigine and second-generation atypical antipsychotics (frequently in combination) as an alternative. The changes in plasma level of lamotrigine across pregnancy are being increasingly well documented based on rigorous studies (Obstet Gynecol Clin North Am. 2018 Sep;45[3]:403-17).

These are welcome data, but the correlation between plasma concentration of lamotrigine and clinical response is a poor one. To date, there are sparse data to suggest that maintaining plasma levels of lithium or lamotrigine at a certain level during pregnancy changes clinical outcome. Following lamotrigine plasma levels during pregnancy seems more like an academic exercise than a procedure associated with particular clinical value.

As in the case of lithium, we never change lamotrigine doses proximate to pregnancy because of the absence of reports of neonatal toxicity associated with using lamotrigine during the peripartum period. The rationale for removing or minimizing the use of an effective medicine proximate to delivery, a period of risk for bipolar women, is lacking.

In 2019, we clearly are seeing a growing use of atypical antipsychotics for the treatment of bipolar disorder during pregnancy frequently coadministered with medicines such as lamotrigine as opposed to lithium. The accumulated data to date on second-generation atypical antipsychotics are not definitive, but increasingly are reassuring in terms of absence of a clear signal for teratogenicity; hence, our comfort in using this class of medicines is only growing, which is important given the prevalence of use of these agents in reproductive-age women.

If there is a single critical guiding principle for the clinician when it comes to managing bipolar women during pregnancy and the postpartum period, it is sustaining euthymia. With the recent focus of the U.S. Preventive Services Task Force on prevention of postpartum depression, nothing is more helpful perhaps than keeping women with bipolar disorder well, both proximate to pregnancy and during an actual pregnancy. Keeping those patients well maximizes the likelihood that they will proceed across the peripartum and into the postpartum period with a level of emotional well-being that optimizes and maximizes positive long-term outcomes for both patients and families.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

 

Careful management of bipolar disorder during pregnancy is critical because for so many patients with this illness, the road to emotional well-being has been a long one, requiring a combination of careful pharmacologic and nonpharmacologic strategies.

KatarzynaBialasiewicz/thinkstockphotos

Half of referrals to our Center for Women’s Mental Health – where we evaluate and treat women before, during, and after pregnancy – are for women who have histories of bipolar disorder. My colleagues and I are asked at continuing medical education programs what we “always do” and “never do” with respect to the treatment of these patients.
 

What about discontinuation of mood stabilizers during pregnancy and risk of relapse?

We never abruptly stop mood stabilizers if a patient has an unplanned pregnancy – a common scenario, with 50% of pregnancies across the country being unplanned across sociodemographic lines – save for sodium valproate, which is a clearly a documented teratogen; it increases risk for organ malformation and behavioral difficulties in exposed offspring. In our center, we typically view the use of sodium valproate in reproductive age women as contraindicated.

One may then question the circumstances under which lithium might be used during pregnancy, because many clinicians are faced with patients who have been exquisite responders to lithium. Such a patient may present with a history of mania, but there are obvious concerns given the historical literature, and even some more recent reports, that describe an increased risk of teratogenicity with fetal exposure to lithium.

Maintenance pharmacotherapy for women with bipolar disorder during pregnancy is so important, not only to decrease the risk of relapse following discontinuation of mood stabilizers, but because recurrence of illness during pregnancy for these patients is a very strong predictor of risk for postpartum depression. Women with bipolar disorder already are at a fivefold increased risk for postpartum depression, so discussion of sustaining euthymia during pregnancy for bipolar women is particularly timely given the focus nationally on treatment and prevention of postpartum depression.
 

In patients with history of mania, what about stopping treatment with lithium and other effective treatments during pregnancy?

Historically, we sometimes divided patients with bipolar disorder into those with “more severe recurrent disease” compared with those with more distant, circumscribed disease. In patients with more remote histories of mood dysregulation, we tended to discontinue treatment with mood stabilizers such as lithium or even newer second-generation atypical antipsychotics to see if patients could at least get through earlier stages of pregnancy before going back on anti-manic treatment.

Our experience now over several decades has revealed that this can be a risky clinical move. What we see is that even in patients with histories of mania years in the past (i.e., a circumscribed episode of mania during college in a woman now 35 years old with intervening sustained well-being), discontinuation of treatment that got patients well can lead to recurrence. Hence, we should not confuse an exquisite response to treatment with long periods of well-being as suggesting that the patient has a less severe form of bipolar disorder and hence the capacity to sustain that well-being when treatment is removed.
 

 

What about increasing/decreasing lithium dose during pregnancy and around time of delivery?

Select patients may be sensitive to changes in plasma levels of lithium, but the literature suggests that the clinical utility of arbitrarily sustaining plasma levels at the upper limit of the accepted range may be of only modest advantage, if any. With this as a backdrop and even while knowing that increased plasma volume of pregnancy is associated with a fall in plasma level of most medications, we do not arbitrarily increase the dose of lithium across pregnancy merely to sustain a level in the absence of a change in clinical symptoms. Indeed, to my knowledge, currently available data supporting a clear correlation of decline in plasma levels and frank change in symptoms during pregnancy are very sparse, if existent.

Earlier work had suggested that lithium dosage should be reduced proximate to delivery, a period characterized by rapid shifts in plasma volume during the acute peripartum period. Because physicians in our center do not alter lithium dose across pregnancy, we never reduce the dose of lithium proximate to delivery because of a theoretical concern for increased risk of either neonatal toxicity or maternal lithium toxicity, which is essentially nonexistent in terms of systematic reports in the literature.

Obvious concerns about lithium during pregnancy have focused on increased risk of teratogenesis, with the earliest reports supporting an increased risk of Epstein’s anomaly (0.05%-0.1%). More recent reports suggest an increased risk of cardiovascular malformations, which according to some investigators may be dose dependent.

For those patients who are exquisitely responsive to lithium, we typically leave them on the medicine and avail ourselves of current fetal echocardiographic evaluation at 16 weeks to 18 weeks to document the integrity of the fetal cardiac anatomy. Although the risk for cardiac malformations associated with lithium exposure during the first trimester is still exceedingly small, it is still extremely reassuring to patients to know that they are safely on the other side of a teratogenic window.
 

What about lamotrigine levels across pregnancy?

The last decade has seen a dramatic decrease in the administration of lithium to women with bipolar disorder, and growing use of both lamotrigine and second-generation atypical antipsychotics (frequently in combination) as an alternative. The changes in plasma level of lamotrigine across pregnancy are being increasingly well documented based on rigorous studies (Obstet Gynecol Clin North Am. 2018 Sep;45[3]:403-17).

These are welcome data, but the correlation between plasma concentration of lamotrigine and clinical response is a poor one. To date, there are sparse data to suggest that maintaining plasma levels of lithium or lamotrigine at a certain level during pregnancy changes clinical outcome. Following lamotrigine plasma levels during pregnancy seems more like an academic exercise than a procedure associated with particular clinical value.

As in the case of lithium, we never change lamotrigine doses proximate to pregnancy because of the absence of reports of neonatal toxicity associated with using lamotrigine during the peripartum period. The rationale for removing or minimizing the use of an effective medicine proximate to delivery, a period of risk for bipolar women, is lacking.

In 2019, we clearly are seeing a growing use of atypical antipsychotics for the treatment of bipolar disorder during pregnancy frequently coadministered with medicines such as lamotrigine as opposed to lithium. The accumulated data to date on second-generation atypical antipsychotics are not definitive, but increasingly are reassuring in terms of absence of a clear signal for teratogenicity; hence, our comfort in using this class of medicines is only growing, which is important given the prevalence of use of these agents in reproductive-age women.

If there is a single critical guiding principle for the clinician when it comes to managing bipolar women during pregnancy and the postpartum period, it is sustaining euthymia. With the recent focus of the U.S. Preventive Services Task Force on prevention of postpartum depression, nothing is more helpful perhaps than keeping women with bipolar disorder well, both proximate to pregnancy and during an actual pregnancy. Keeping those patients well maximizes the likelihood that they will proceed across the peripartum and into the postpartum period with a level of emotional well-being that optimizes and maximizes positive long-term outcomes for both patients and families.
 

Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He is also the Edmund and Carroll Carpenter professor of psychiatry at Harvard Medical School. He has been a consultant to manufacturers of psychiatric medications. Email Dr. Cohen at [email protected].

My son and I used to play a game called CASHFLOW. It was invented by Robert Kiyosaki, the real estate magnate who originated the “Rich Dad Poor Dad” book series to educate the masses on the basics of real estate investing.

Courtesy Rich Dad Company

The object of the game was to acquire enough passive income to become independent of active income like salary. The hope was that by playing the game, participants would recognize the advantages of passive income and become entrepreneurs in real estate or business. The winner was no longer an employee, but happily self-employed and out of the rat race.

Alas, the lesson was lost on me and my son. Both of us are still very much in the rat race and dependent on salary.

But a rat race can be more than just a competitive quest for financial gain. In politics, the quest is more for power. In sports, the quest includes championships. In academic medicine – and hematology is usually practiced in an academic setting – the quest is often for power and prestige. Training for our hematologic quest began in high school.

In high school, superior grades were a given, but we also worked to excel in sports, extracurricular activities, and standardized tests in order to get into the best universities. The cycle was then repeated to allow entry into the best medical schools. The old adage that students who finished last in their medical school class are still addressed as “Doctor” notwithstanding, most of us pushed ourselves beyond good grades to volunteer work, research activities, and prestigious clerkships to ensure that we matched at the best residency programs. There, those inclined to hematology cozied up to influential faculty by helping with their research in order to obtain the cherished letter of recommendation that promised admission to the best fellowship program, where the cycle was again repeated in the hope of landing a position in the best academic medical center.

Through these pursuits, young recruits to medical academia are primed and ready to enter a rat race of individual accomplishment. The academic rat race is a particularly pernicious result of our training to be the best, and the “best” hematologists are found at the podium, not in the exam room.

Not content to be recognized for clinical excellence by their patients, academic hematologists often aspire more to be recognized for content expertise by their peers. Through the noble pursuit of advancing science, peer recognition bestows prestige and power in the form of promotions, grants, advisory boards, consultancies, and speaking opportunities all over the globe. For some, the academic rat race validates a life dedicated to being the best.

However, the demands of patient care can interfere with academic pursuits and stand as impediments to the march of science, with its attendant rewards in power and prestige. The most common complaint I get from my team is the inability to fully participate in all that is required to succeed academically because of clinical responsibilities. The difficulty is worsened when financial realities require even more time spent in the clinic to generate income. This makes it hard enough to keep a healthy balance between research and patient care. When the pressures of clinical and academic hematology are combined with the responsibility of family, the rat race can begin to lead to burnout.


A rat race forces us to compare ourselves to others, and we often find ourselves wanting. There is always someone who seems wealthier and wiser than we are. Our training often compels us to compete with whoever it is we are comparing ourselves to. That competition simultaneously drives us toward a laudable goal and away from a balanced, happy life.

Theodore Roosevelt said “Comparison is the thief of joy,” and that certainly seems to be the case among medical professionals. As physicians, we do not lack for wealth, unless we compare ourselves to those who have more. We do not lack for wisdom, unless we compare ourselves to those who have more. We’d see that we really lack very little and occupy a privileged place in society if we only took the time to be grateful for having had the talent and support to do so.

I enjoyed playing CASHFLOW when I was younger and naively thought that either my son or I might materially benefit from its lessons. I realize now that the real enjoyment of playing was not to win or to get rich, but rather to spend time with my son. Likewise, our training got us where we are, and it will sustain a happy fulfilling career, but it will also consume us if we let go of why we started playing the game in the first place.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematology and medical oncology at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

My son and I used to play a game called CASHFLOW. It was invented by Robert Kiyosaki, the real estate magnate who originated the “Rich Dad Poor Dad” book series to educate the masses on the basics of real estate investing.

Courtesy Rich Dad Company

The object of the game was to acquire enough passive income to become independent of active income like salary. The hope was that by playing the game, participants would recognize the advantages of passive income and become entrepreneurs in real estate or business. The winner was no longer an employee, but happily self-employed and out of the rat race.

Alas, the lesson was lost on me and my son. Both of us are still very much in the rat race and dependent on salary.

But a rat race can be more than just a competitive quest for financial gain. In politics, the quest is more for power. In sports, the quest includes championships. In academic medicine – and hematology is usually practiced in an academic setting – the quest is often for power and prestige. Training for our hematologic quest began in high school.

In high school, superior grades were a given, but we also worked to excel in sports, extracurricular activities, and standardized tests in order to get into the best universities. The cycle was then repeated to allow entry into the best medical schools. The old adage that students who finished last in their medical school class are still addressed as “Doctor” notwithstanding, most of us pushed ourselves beyond good grades to volunteer work, research activities, and prestigious clerkships to ensure that we matched at the best residency programs. There, those inclined to hematology cozied up to influential faculty by helping with their research in order to obtain the cherished letter of recommendation that promised admission to the best fellowship program, where the cycle was again repeated in the hope of landing a position in the best academic medical center.

Through these pursuits, young recruits to medical academia are primed and ready to enter a rat race of individual accomplishment. The academic rat race is a particularly pernicious result of our training to be the best, and the “best” hematologists are found at the podium, not in the exam room.

Not content to be recognized for clinical excellence by their patients, academic hematologists often aspire more to be recognized for content expertise by their peers. Through the noble pursuit of advancing science, peer recognition bestows prestige and power in the form of promotions, grants, advisory boards, consultancies, and speaking opportunities all over the globe. For some, the academic rat race validates a life dedicated to being the best.

However, the demands of patient care can interfere with academic pursuits and stand as impediments to the march of science, with its attendant rewards in power and prestige. The most common complaint I get from my team is the inability to fully participate in all that is required to succeed academically because of clinical responsibilities. The difficulty is worsened when financial realities require even more time spent in the clinic to generate income. This makes it hard enough to keep a healthy balance between research and patient care. When the pressures of clinical and academic hematology are combined with the responsibility of family, the rat race can begin to lead to burnout.


A rat race forces us to compare ourselves to others, and we often find ourselves wanting. There is always someone who seems wealthier and wiser than we are. Our training often compels us to compete with whoever it is we are comparing ourselves to. That competition simultaneously drives us toward a laudable goal and away from a balanced, happy life.

Theodore Roosevelt said “Comparison is the thief of joy,” and that certainly seems to be the case among medical professionals. As physicians, we do not lack for wealth, unless we compare ourselves to those who have more. We do not lack for wisdom, unless we compare ourselves to those who have more. We’d see that we really lack very little and occupy a privileged place in society if we only took the time to be grateful for having had the talent and support to do so.

I enjoyed playing CASHFLOW when I was younger and naively thought that either my son or I might materially benefit from its lessons. I realize now that the real enjoyment of playing was not to win or to get rich, but rather to spend time with my son. Likewise, our training got us where we are, and it will sustain a happy fulfilling career, but it will also consume us if we let go of why we started playing the game in the first place.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematology and medical oncology at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

My son and I used to play a game called CASHFLOW. It was invented by Robert Kiyosaki, the real estate magnate who originated the “Rich Dad Poor Dad” book series to educate the masses on the basics of real estate investing.

Courtesy Rich Dad Company

The object of the game was to acquire enough passive income to become independent of active income like salary. The hope was that by playing the game, participants would recognize the advantages of passive income and become entrepreneurs in real estate or business. The winner was no longer an employee, but happily self-employed and out of the rat race.

Alas, the lesson was lost on me and my son. Both of us are still very much in the rat race and dependent on salary.

But a rat race can be more than just a competitive quest for financial gain. In politics, the quest is more for power. In sports, the quest includes championships. In academic medicine – and hematology is usually practiced in an academic setting – the quest is often for power and prestige. Training for our hematologic quest began in high school.

In high school, superior grades were a given, but we also worked to excel in sports, extracurricular activities, and standardized tests in order to get into the best universities. The cycle was then repeated to allow entry into the best medical schools. The old adage that students who finished last in their medical school class are still addressed as “Doctor” notwithstanding, most of us pushed ourselves beyond good grades to volunteer work, research activities, and prestigious clerkships to ensure that we matched at the best residency programs. There, those inclined to hematology cozied up to influential faculty by helping with their research in order to obtain the cherished letter of recommendation that promised admission to the best fellowship program, where the cycle was again repeated in the hope of landing a position in the best academic medical center.

Through these pursuits, young recruits to medical academia are primed and ready to enter a rat race of individual accomplishment. The academic rat race is a particularly pernicious result of our training to be the best, and the “best” hematologists are found at the podium, not in the exam room.

Not content to be recognized for clinical excellence by their patients, academic hematologists often aspire more to be recognized for content expertise by their peers. Through the noble pursuit of advancing science, peer recognition bestows prestige and power in the form of promotions, grants, advisory boards, consultancies, and speaking opportunities all over the globe. For some, the academic rat race validates a life dedicated to being the best.

However, the demands of patient care can interfere with academic pursuits and stand as impediments to the march of science, with its attendant rewards in power and prestige. The most common complaint I get from my team is the inability to fully participate in all that is required to succeed academically because of clinical responsibilities. The difficulty is worsened when financial realities require even more time spent in the clinic to generate income. This makes it hard enough to keep a healthy balance between research and patient care. When the pressures of clinical and academic hematology are combined with the responsibility of family, the rat race can begin to lead to burnout.


A rat race forces us to compare ourselves to others, and we often find ourselves wanting. There is always someone who seems wealthier and wiser than we are. Our training often compels us to compete with whoever it is we are comparing ourselves to. That competition simultaneously drives us toward a laudable goal and away from a balanced, happy life.

Theodore Roosevelt said “Comparison is the thief of joy,” and that certainly seems to be the case among medical professionals. As physicians, we do not lack for wealth, unless we compare ourselves to those who have more. We do not lack for wisdom, unless we compare ourselves to those who have more. We’d see that we really lack very little and occupy a privileged place in society if we only took the time to be grateful for having had the talent and support to do so.

I enjoyed playing CASHFLOW when I was younger and naively thought that either my son or I might materially benefit from its lessons. I realize now that the real enjoyment of playing was not to win or to get rich, but rather to spend time with my son. Likewise, our training got us where we are, and it will sustain a happy fulfilling career, but it will also consume us if we let go of why we started playing the game in the first place.

Dr. Kalaycio is editor in chief of Hematology News. He chairs the department of hematology and medical oncology at Cleveland Clinic Taussig Cancer Institute. Contact him at [email protected].

Spring has always been an exciting time for gastroenterologists, beginning with Colon Cancer Awareness month in March and finishing with our flagship scientific meeting in May. Gastroenterologists have led the fight against colon cancer; publishing seminal research (the National Polyp Study was published April 1, 26 years ago), building a distributed network of high-value ambulatory endoscopy centers, educating primary care physicians and the public about screening and early detection, and advocating continuously to make cancer prevention affordable for all people.

This year, AGA has sponsored two meetings where truly ground-breaking science was presented and we have highlighted them on our front page this month. On March 23-24, the AGA worked with the European Society of Neurogastroenterology and Motility to bring you the 8th annual Gut Microbiota for Health World Summit in Miami. World leaders in microbiome research presented a breath-taking array of clinically relevant research on topics that impact your patients. Dr. Stanley Hazen (Cleveland Clinic) presented his work linking dietary choices to a blood marker of atherosclerotic risk (TMAO) where the key associative link is the diet-influenced microbiome.

The AGA also brought you the 10th annual AGA Tech Summit from San Francisco, April 10-12. This meeting has become the best single source to learn about new technology emerging in our field. In this issue of GI & Hepatology News, we highlight two presentations about managing visceral pain with virtual reality technology and how predictive analysis is being used to personalize IBD therapy.

Spring wraps up with DDW^® in San Diego (May 18-21). DDW begins with the AGA Postgraduate Course (May 18-19) that provides the best annual summary of both gastroenterology and hepatology combined in a single setting. The live meeting will feature key updates and new science about biosimilars, cancer prevention, celiac disease, endoscopy, the microbiome, hepatology, IBD, nutrition, and care delivery.

As usual, GIHN will feature key presentations from DDW including those from the Presidential Plenary session (Monday morning May 20).

John I. Allen, MD, MBA, AGAF
Editor in Chief

Spring has always been an exciting time for gastroenterologists, beginning with Colon Cancer Awareness month in March and finishing with our flagship scientific meeting in May. Gastroenterologists have led the fight against colon cancer; publishing seminal research (the National Polyp Study was published April 1, 26 years ago), building a distributed network of high-value ambulatory endoscopy centers, educating primary care physicians and the public about screening and early detection, and advocating continuously to make cancer prevention affordable for all people.

This year, AGA has sponsored two meetings where truly ground-breaking science was presented and we have highlighted them on our front page this month. On March 23-24, the AGA worked with the European Society of Neurogastroenterology and Motility to bring you the 8th annual Gut Microbiota for Health World Summit in Miami. World leaders in microbiome research presented a breath-taking array of clinically relevant research on topics that impact your patients. Dr. Stanley Hazen (Cleveland Clinic) presented his work linking dietary choices to a blood marker of atherosclerotic risk (TMAO) where the key associative link is the diet-influenced microbiome.

The AGA also brought you the 10th annual AGA Tech Summit from San Francisco, April 10-12. This meeting has become the best single source to learn about new technology emerging in our field. In this issue of GI & Hepatology News, we highlight two presentations about managing visceral pain with virtual reality technology and how predictive analysis is being used to personalize IBD therapy.

Spring wraps up with DDW^® in San Diego (May 18-21). DDW begins with the AGA Postgraduate Course (May 18-19) that provides the best annual summary of both gastroenterology and hepatology combined in a single setting. The live meeting will feature key updates and new science about biosimilars, cancer prevention, celiac disease, endoscopy, the microbiome, hepatology, IBD, nutrition, and care delivery.

As usual, GIHN will feature key presentations from DDW including those from the Presidential Plenary session (Monday morning May 20).

John I. Allen, MD, MBA, AGAF
Editor in Chief

Spring has always been an exciting time for gastroenterologists, beginning with Colon Cancer Awareness month in March and finishing with our flagship scientific meeting in May. Gastroenterologists have led the fight against colon cancer; publishing seminal research (the National Polyp Study was published April 1, 26 years ago), building a distributed network of high-value ambulatory endoscopy centers, educating primary care physicians and the public about screening and early detection, and advocating continuously to make cancer prevention affordable for all people.

This year, AGA has sponsored two meetings where truly ground-breaking science was presented and we have highlighted them on our front page this month. On March 23-24, the AGA worked with the European Society of Neurogastroenterology and Motility to bring you the 8th annual Gut Microbiota for Health World Summit in Miami. World leaders in microbiome research presented a breath-taking array of clinically relevant research on topics that impact your patients. Dr. Stanley Hazen (Cleveland Clinic) presented his work linking dietary choices to a blood marker of atherosclerotic risk (TMAO) where the key associative link is the diet-influenced microbiome.

The AGA also brought you the 10th annual AGA Tech Summit from San Francisco, April 10-12. This meeting has become the best single source to learn about new technology emerging in our field. In this issue of GI & Hepatology News, we highlight two presentations about managing visceral pain with virtual reality technology and how predictive analysis is being used to personalize IBD therapy.

Spring wraps up with DDW^® in San Diego (May 18-21). DDW begins with the AGA Postgraduate Course (May 18-19) that provides the best annual summary of both gastroenterology and hepatology combined in a single setting. The live meeting will feature key updates and new science about biosimilars, cancer prevention, celiac disease, endoscopy, the microbiome, hepatology, IBD, nutrition, and care delivery.

As usual, GIHN will feature key presentations from DDW including those from the Presidential Plenary session (Monday morning May 20).

John I. Allen, MD, MBA, AGAF
Editor in Chief

 

The clinical scenario is as follows: A 62-year-old woman comes to see me for a new diagnosis of grade 1 endometrial cancer. She has a normal body mass index of 24 kg/m², a history of four prior full-term pregnancies, no family history of malignancy, and no medical comorbidities. She is otherwise a specimen of good health, and has no clear identifiable risk factors for this malignancy. She then reports that she transitioned through menopause at age 52 years and developed severe hot flashes with sleep and mood disturbance. She did not wish to take conventional hormone replacement therapy (HT) because she had heard it causes cancer. She subsequently researched the Internet and found a provider who has been prescribing compounded bioidentical hormone therapy (CBHT) for her for the past 10 years. She submits saliva for testing of her estrogen levels, and the provider uses this data to compound the appropriate doses of “natural” estrogens and testosterone for her which she applies via vaginal or transdermal creams. She has been prescribed a progesterone suppository, but she doesn’t always take that because she doesn’t notice that it has any effect on how she feels. “Doctor, did my bioidentical hormones give me this uterine cancer?”

Alexander Raths/Fotolia

My answer is, of course, I don’t know. Cancer is a complex disease with a complex array of causative and promoting factors. However, we do know that taking estrogen unopposed with adequate progesterone can cause the development of uterine cancer and its precursor state.¹ If those bioidentical estrogens were effective at controlling her menopausal symptoms, they likely were effective at stimulating her endometrium at the same time.

What are compounded bioidentical hormones?

The term “bioidentical” refers to having the same molecular structure as that which is found in the human body. Examples of bioidentical estrogens include 17-beta-estradiol, estrone, and estriol – which are produced from yams and soy. Micronized progesterone is an example of a bioidentical progesterone. Many of these drugs are approved by the Food and Drug Administration, and prescribed and dispensed by conventional pharmacies.

An alternative, and increasingly popular, version of bioidentical hormones are CBHs. It should be recognized that this is a marketing, and not a scientific, term. These products utilize hormones, in some cases FDA-approved bioidentical hormones, that are broken down and blended by specialized pharmacies and reconstituted (compounded) into different, and sometimes “customized,” dosing and delivery methods (such as capsules, patches, gels, creams, lozenges, suppositories). Frequently used compounded products utilize multiple formulations of estrogens in doublets and triplets as well as progesterone, testosterone, and dehydroepiandrosterone.

How do they differ from synthetic hormones?

Distributors of CBHs state that they differ from conventional HT (synthetic and bioidentical) because of the customization process from which they promise greater efficacy and a sense of personalized medicine. The distributors frequently utilize assays from saliva, blood, vaginal secretions, and urine to measure a woman’s hormone levels, and titrate her compounded formulation based on those results. It should be noted that there is no data to support that titration of hormones to blood, salivary, or urine levels is efficacious or ensures greater safety than titration based on symptom management.

 

Critics of CBHT, which includes the North American Menopause Society² and the American College of Obstetricians and Gynecologists,³ highlight that the main difference between CBHT and HT is lack of FDA regulation over the CBHT industry. Many of these agents are delivered transdermally and therefore are classified as “dietary supplements.” As such, they do not require FDA regulation or proof of safety or efficacy.

Lack of FDA approval allows CBHs to be distributed without package inserts and boxed warnings (such as the standard warnings about MI, venous thromboembolic events, and breast cancer). The absence of FDA approval also allows them to avoid FDA-regulated guarantees about purity, potency, and efficacy. Audits of CBHs have shown high rates of discrepancy between stated and measured potency, including observations of both much lower and much higher than stated strength.⁴

Why would dosing accuracy be important in hormone therapy prescription? If a woman taking estrogen therapy is not receiving adequate cotreatment with progesterone because of either omission or a subtherapeutic product, she increases her risk for endometrial cancer.

What drives patients’ decision to use compounded bioidentical hormones?

After the Womens’ Health Initiative study was published in 2002⁵, all FDA-regulated estrogen preparations were required to carry specific warnings, particularly in relation to the increased risk for MI, venous thromboembolic events, and breast cancer. There was a clear uptake in use of CBHT after this study was reported. By avoiding FDA regulations, distributors of CBHTs may have avoided providing Womens’ Health Initiative information to patients. The absence of an insert with a written warning, in and of itself, makes these preparations seem safer to the patient.

But is it entirely a lack of information that drives demand for CBHTs? Surveys of current or former users suggest the motivations are more complex than that. A survey of 21 past or present CBHT users inquired about reasons for use of CBHT over conventional HT.⁶ Their responses were categorized as either push motivations away from conventional therapy versus pull motivations toward CBHT. About 95% of current and former users cited distrust of the biomedicine and pharmaceutical industry as reasons for use of CBHT. Fear about the safety of conventional HT, particularly with respect to cancer risk, also was strongly cited at 81%. Motivations pulling toward CBHT included its efficacy (76%) and perception that CBHT is “safer” than conventional HT (76%).

Women in this study also appreciated the tailored, individualized approach that often is associated with CBHT, in which providers spend long consultations discussing individual patient needs and concerns. They enjoy the idea of a customized blend that is created, as opposed to a standard dosing regimen, and intuitively trust the reliability of blood and saliva testing as a prescriptive tool.

Are bioidentical hormones safe with respect to cancer risk?

Hormones themselves are not inert substances, including those derived in vivo and those from plants. They have powerful effects in the human body and can promote malignant transformation or proliferation, alter metabolic pathways, stimulate vascular tone, influence coagulation pathways, along with many other effects. A hormone’s potential for deleterious effect can be present regardless of how that hormone is synthesized, procured, or prepared. While there are no data to suggest that CBHT is associated with increased cancer risk, compared with conventional HT, there are by no means any data to suggest it is safer. Unopposed compounded estrogens place women at increased risk for endometrial cancers, and the prolonged use of hormonal therapy, compounded or otherwise, after menopause increases the risk for breast cancer.

 

How should we counsel patients?

Patients who desire compounded bioidentical hormone preparations should be counseled that little is known about the safety of these preparations, compared with conventional hormone preparations. The fact that the components are often plant based rather than synthetic does not inherently alter their potential negative impact on biologic pathways. Patients should be educated regarding the difference between FDA-regulated products and nonregulated products so that they can understand that lack of a boxed warning on a non-FDA regulated product does not mean an absence of risk. Women should be informed of the potential inaccuracies in dosing and strength of the CBH preparations they receive.

We should recognize that our patients strongly desire a relationship with their provider in which they are listened to, understood, and treated as individuals. If conversations regarding hormone use are approached with these principles, we will optimize the likelihood our patients are receptive to the highest quality information and not pulled in the direction of unregulated products.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She reported that she had no conflicts of interest. Email Dr. Rossi at [email protected].

References:

1. Maturitas. 2014 Jan;77(1):4-6.

2. Menopause. 2014 Dec;21(12):1298-300.

3. Fertil Steril. 2012 Aug;98(2):308-12.

4. Report: Limited FDA survey of compounded drug products (Silver Spring, Md.: U.S. Food and Drug Administration, 2009).

5. JAMA. 2002;288(3):321-33.

6. BMC Womens Health. 2017 Oct 2;17(1):97.

 

The clinical scenario is as follows: A 62-year-old woman comes to see me for a new diagnosis of grade 1 endometrial cancer. She has a normal body mass index of 24 kg/m², a history of four prior full-term pregnancies, no family history of malignancy, and no medical comorbidities. She is otherwise a specimen of good health, and has no clear identifiable risk factors for this malignancy. She then reports that she transitioned through menopause at age 52 years and developed severe hot flashes with sleep and mood disturbance. She did not wish to take conventional hormone replacement therapy (HT) because she had heard it causes cancer. She subsequently researched the Internet and found a provider who has been prescribing compounded bioidentical hormone therapy (CBHT) for her for the past 10 years. She submits saliva for testing of her estrogen levels, and the provider uses this data to compound the appropriate doses of “natural” estrogens and testosterone for her which she applies via vaginal or transdermal creams. She has been prescribed a progesterone suppository, but she doesn’t always take that because she doesn’t notice that it has any effect on how she feels. “Doctor, did my bioidentical hormones give me this uterine cancer?”

Alexander Raths/Fotolia

My answer is, of course, I don’t know. Cancer is a complex disease with a complex array of causative and promoting factors. However, we do know that taking estrogen unopposed with adequate progesterone can cause the development of uterine cancer and its precursor state.¹ If those bioidentical estrogens were effective at controlling her menopausal symptoms, they likely were effective at stimulating her endometrium at the same time.

What are compounded bioidentical hormones?

The term “bioidentical” refers to having the same molecular structure as that which is found in the human body. Examples of bioidentical estrogens include 17-beta-estradiol, estrone, and estriol – which are produced from yams and soy. Micronized progesterone is an example of a bioidentical progesterone. Many of these drugs are approved by the Food and Drug Administration, and prescribed and dispensed by conventional pharmacies.

An alternative, and increasingly popular, version of bioidentical hormones are CBHs. It should be recognized that this is a marketing, and not a scientific, term. These products utilize hormones, in some cases FDA-approved bioidentical hormones, that are broken down and blended by specialized pharmacies and reconstituted (compounded) into different, and sometimes “customized,” dosing and delivery methods (such as capsules, patches, gels, creams, lozenges, suppositories). Frequently used compounded products utilize multiple formulations of estrogens in doublets and triplets as well as progesterone, testosterone, and dehydroepiandrosterone.

How do they differ from synthetic hormones?

Distributors of CBHs state that they differ from conventional HT (synthetic and bioidentical) because of the customization process from which they promise greater efficacy and a sense of personalized medicine. The distributors frequently utilize assays from saliva, blood, vaginal secretions, and urine to measure a woman’s hormone levels, and titrate her compounded formulation based on those results. It should be noted that there is no data to support that titration of hormones to blood, salivary, or urine levels is efficacious or ensures greater safety than titration based on symptom management.

 

Critics of CBHT, which includes the North American Menopause Society² and the American College of Obstetricians and Gynecologists,³ highlight that the main difference between CBHT and HT is lack of FDA regulation over the CBHT industry. Many of these agents are delivered transdermally and therefore are classified as “dietary supplements.” As such, they do not require FDA regulation or proof of safety or efficacy.

Lack of FDA approval allows CBHs to be distributed without package inserts and boxed warnings (such as the standard warnings about MI, venous thromboembolic events, and breast cancer). The absence of FDA approval also allows them to avoid FDA-regulated guarantees about purity, potency, and efficacy. Audits of CBHs have shown high rates of discrepancy between stated and measured potency, including observations of both much lower and much higher than stated strength.⁴

Why would dosing accuracy be important in hormone therapy prescription? If a woman taking estrogen therapy is not receiving adequate cotreatment with progesterone because of either omission or a subtherapeutic product, she increases her risk for endometrial cancer.

What drives patients’ decision to use compounded bioidentical hormones?

After the Womens’ Health Initiative study was published in 2002⁵, all FDA-regulated estrogen preparations were required to carry specific warnings, particularly in relation to the increased risk for MI, venous thromboembolic events, and breast cancer. There was a clear uptake in use of CBHT after this study was reported. By avoiding FDA regulations, distributors of CBHTs may have avoided providing Womens’ Health Initiative information to patients. The absence of an insert with a written warning, in and of itself, makes these preparations seem safer to the patient.

But is it entirely a lack of information that drives demand for CBHTs? Surveys of current or former users suggest the motivations are more complex than that. A survey of 21 past or present CBHT users inquired about reasons for use of CBHT over conventional HT.⁶ Their responses were categorized as either push motivations away from conventional therapy versus pull motivations toward CBHT. About 95% of current and former users cited distrust of the biomedicine and pharmaceutical industry as reasons for use of CBHT. Fear about the safety of conventional HT, particularly with respect to cancer risk, also was strongly cited at 81%. Motivations pulling toward CBHT included its efficacy (76%) and perception that CBHT is “safer” than conventional HT (76%).

Women in this study also appreciated the tailored, individualized approach that often is associated with CBHT, in which providers spend long consultations discussing individual patient needs and concerns. They enjoy the idea of a customized blend that is created, as opposed to a standard dosing regimen, and intuitively trust the reliability of blood and saliva testing as a prescriptive tool.

Are bioidentical hormones safe with respect to cancer risk?

Hormones themselves are not inert substances, including those derived in vivo and those from plants. They have powerful effects in the human body and can promote malignant transformation or proliferation, alter metabolic pathways, stimulate vascular tone, influence coagulation pathways, along with many other effects. A hormone’s potential for deleterious effect can be present regardless of how that hormone is synthesized, procured, or prepared. While there are no data to suggest that CBHT is associated with increased cancer risk, compared with conventional HT, there are by no means any data to suggest it is safer. Unopposed compounded estrogens place women at increased risk for endometrial cancers, and the prolonged use of hormonal therapy, compounded or otherwise, after menopause increases the risk for breast cancer.

 

How should we counsel patients?

Patients who desire compounded bioidentical hormone preparations should be counseled that little is known about the safety of these preparations, compared with conventional hormone preparations. The fact that the components are often plant based rather than synthetic does not inherently alter their potential negative impact on biologic pathways. Patients should be educated regarding the difference between FDA-regulated products and nonregulated products so that they can understand that lack of a boxed warning on a non-FDA regulated product does not mean an absence of risk. Women should be informed of the potential inaccuracies in dosing and strength of the CBH preparations they receive.

We should recognize that our patients strongly desire a relationship with their provider in which they are listened to, understood, and treated as individuals. If conversations regarding hormone use are approached with these principles, we will optimize the likelihood our patients are receptive to the highest quality information and not pulled in the direction of unregulated products.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She reported that she had no conflicts of interest. Email Dr. Rossi at [email protected].

References:

1. Maturitas. 2014 Jan;77(1):4-6.

2. Menopause. 2014 Dec;21(12):1298-300.

3. Fertil Steril. 2012 Aug;98(2):308-12.

4. Report: Limited FDA survey of compounded drug products (Silver Spring, Md.: U.S. Food and Drug Administration, 2009).

5. JAMA. 2002;288(3):321-33.

6. BMC Womens Health. 2017 Oct 2;17(1):97.

 

The clinical scenario is as follows: A 62-year-old woman comes to see me for a new diagnosis of grade 1 endometrial cancer. She has a normal body mass index of 24 kg/m², a history of four prior full-term pregnancies, no family history of malignancy, and no medical comorbidities. She is otherwise a specimen of good health, and has no clear identifiable risk factors for this malignancy. She then reports that she transitioned through menopause at age 52 years and developed severe hot flashes with sleep and mood disturbance. She did not wish to take conventional hormone replacement therapy (HT) because she had heard it causes cancer. She subsequently researched the Internet and found a provider who has been prescribing compounded bioidentical hormone therapy (CBHT) for her for the past 10 years. She submits saliva for testing of her estrogen levels, and the provider uses this data to compound the appropriate doses of “natural” estrogens and testosterone for her which she applies via vaginal or transdermal creams. She has been prescribed a progesterone suppository, but she doesn’t always take that because she doesn’t notice that it has any effect on how she feels. “Doctor, did my bioidentical hormones give me this uterine cancer?”

Alexander Raths/Fotolia

My answer is, of course, I don’t know. Cancer is a complex disease with a complex array of causative and promoting factors. However, we do know that taking estrogen unopposed with adequate progesterone can cause the development of uterine cancer and its precursor state.¹ If those bioidentical estrogens were effective at controlling her menopausal symptoms, they likely were effective at stimulating her endometrium at the same time.

What are compounded bioidentical hormones?

The term “bioidentical” refers to having the same molecular structure as that which is found in the human body. Examples of bioidentical estrogens include 17-beta-estradiol, estrone, and estriol – which are produced from yams and soy. Micronized progesterone is an example of a bioidentical progesterone. Many of these drugs are approved by the Food and Drug Administration, and prescribed and dispensed by conventional pharmacies.

An alternative, and increasingly popular, version of bioidentical hormones are CBHs. It should be recognized that this is a marketing, and not a scientific, term. These products utilize hormones, in some cases FDA-approved bioidentical hormones, that are broken down and blended by specialized pharmacies and reconstituted (compounded) into different, and sometimes “customized,” dosing and delivery methods (such as capsules, patches, gels, creams, lozenges, suppositories). Frequently used compounded products utilize multiple formulations of estrogens in doublets and triplets as well as progesterone, testosterone, and dehydroepiandrosterone.

How do they differ from synthetic hormones?

Distributors of CBHs state that they differ from conventional HT (synthetic and bioidentical) because of the customization process from which they promise greater efficacy and a sense of personalized medicine. The distributors frequently utilize assays from saliva, blood, vaginal secretions, and urine to measure a woman’s hormone levels, and titrate her compounded formulation based on those results. It should be noted that there is no data to support that titration of hormones to blood, salivary, or urine levels is efficacious or ensures greater safety than titration based on symptom management.

 

Critics of CBHT, which includes the North American Menopause Society² and the American College of Obstetricians and Gynecologists,³ highlight that the main difference between CBHT and HT is lack of FDA regulation over the CBHT industry. Many of these agents are delivered transdermally and therefore are classified as “dietary supplements.” As such, they do not require FDA regulation or proof of safety or efficacy.

Lack of FDA approval allows CBHs to be distributed without package inserts and boxed warnings (such as the standard warnings about MI, venous thromboembolic events, and breast cancer). The absence of FDA approval also allows them to avoid FDA-regulated guarantees about purity, potency, and efficacy. Audits of CBHs have shown high rates of discrepancy between stated and measured potency, including observations of both much lower and much higher than stated strength.⁴

Why would dosing accuracy be important in hormone therapy prescription? If a woman taking estrogen therapy is not receiving adequate cotreatment with progesterone because of either omission or a subtherapeutic product, she increases her risk for endometrial cancer.

What drives patients’ decision to use compounded bioidentical hormones?

After the Womens’ Health Initiative study was published in 2002⁵, all FDA-regulated estrogen preparations were required to carry specific warnings, particularly in relation to the increased risk for MI, venous thromboembolic events, and breast cancer. There was a clear uptake in use of CBHT after this study was reported. By avoiding FDA regulations, distributors of CBHTs may have avoided providing Womens’ Health Initiative information to patients. The absence of an insert with a written warning, in and of itself, makes these preparations seem safer to the patient.

But is it entirely a lack of information that drives demand for CBHTs? Surveys of current or former users suggest the motivations are more complex than that. A survey of 21 past or present CBHT users inquired about reasons for use of CBHT over conventional HT.⁶ Their responses were categorized as either push motivations away from conventional therapy versus pull motivations toward CBHT. About 95% of current and former users cited distrust of the biomedicine and pharmaceutical industry as reasons for use of CBHT. Fear about the safety of conventional HT, particularly with respect to cancer risk, also was strongly cited at 81%. Motivations pulling toward CBHT included its efficacy (76%) and perception that CBHT is “safer” than conventional HT (76%).

Women in this study also appreciated the tailored, individualized approach that often is associated with CBHT, in which providers spend long consultations discussing individual patient needs and concerns. They enjoy the idea of a customized blend that is created, as opposed to a standard dosing regimen, and intuitively trust the reliability of blood and saliva testing as a prescriptive tool.

Are bioidentical hormones safe with respect to cancer risk?

Hormones themselves are not inert substances, including those derived in vivo and those from plants. They have powerful effects in the human body and can promote malignant transformation or proliferation, alter metabolic pathways, stimulate vascular tone, influence coagulation pathways, along with many other effects. A hormone’s potential for deleterious effect can be present regardless of how that hormone is synthesized, procured, or prepared. While there are no data to suggest that CBHT is associated with increased cancer risk, compared with conventional HT, there are by no means any data to suggest it is safer. Unopposed compounded estrogens place women at increased risk for endometrial cancers, and the prolonged use of hormonal therapy, compounded or otherwise, after menopause increases the risk for breast cancer.

 

How should we counsel patients?

Patients who desire compounded bioidentical hormone preparations should be counseled that little is known about the safety of these preparations, compared with conventional hormone preparations. The fact that the components are often plant based rather than synthetic does not inherently alter their potential negative impact on biologic pathways. Patients should be educated regarding the difference between FDA-regulated products and nonregulated products so that they can understand that lack of a boxed warning on a non-FDA regulated product does not mean an absence of risk. Women should be informed of the potential inaccuracies in dosing and strength of the CBH preparations they receive.

We should recognize that our patients strongly desire a relationship with their provider in which they are listened to, understood, and treated as individuals. If conversations regarding hormone use are approached with these principles, we will optimize the likelihood our patients are receptive to the highest quality information and not pulled in the direction of unregulated products.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She reported that she had no conflicts of interest. Email Dr. Rossi at [email protected].

References:

1. Maturitas. 2014 Jan;77(1):4-6.

2. Menopause. 2014 Dec;21(12):1298-300.

3. Fertil Steril. 2012 Aug;98(2):308-12.

4. Report: Limited FDA survey of compounded drug products (Silver Spring, Md.: U.S. Food and Drug Administration, 2009).

5. JAMA. 2002;288(3):321-33.

6. BMC Womens Health. 2017 Oct 2;17(1):97.