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Doctors sound off about future of medical meetings
As most 2020 medical conferences have, one by one, been canceled or rescheduled as virtual meetings in the time of a pandemic, some physicians and other healthcare professionals are wondering if this is the year that will change the scene forever.
Amid the choruses of resignation (“Unfortunately, it’s the right thing to do.”) and optimism (“See you next year!”), there have been plenty of voices describing another broad sentiment – that all was not well with medical meetings even before the coronavirus.
One dominant criticism is that there are too many meetings.
Indeed, there are many, many meetings. During 2005–2015, there were 30,000-plus medical meetings in the United States, according to a report from the Healthcare Convention and Exhibitors Association.
Most of those are of little value, tweeted Dhruv Khullar, MD, an internist at Weill Cornell Medicine, New York City (@DhruvKhullar): “One possible consequence of cancelling so many meetings due to #COVID19 is that we realize we probably don’t need most of them.”
The tweet was liked 1.9K times, which is high for a medical post. Comments were mostly in agreement, with some skepticism.
Michaela West, MD, PhD, a surgeon at North Memorial Health, Minneapolis, Minnesota, responded (@MichaelaWst): “Agree. COVID-19 may forever change our perspective regarding medical professional meetings.”
Nwando Olayiwola, MD, chair of family medicine, Ohio State University, Columbus, strongly agreed (@DrNwando): “This is the tweet I wish I tweeted.”
However, Kelly Swords, MD, MPH, urologist, University of California, San Diego, in a dissenting opinion, stated the obvious (@k_dagger): “Except there is no substitute for human interaction.”
Worth the Effort?
The cancellation of medical meetings has given those who regularly attend an opportunity to reassess their value and to question the worth of the effort involved in attending in person.
David Steensma, MD, hematologist-oncologist, Harvard Medical School, Boston, (@DavidSteensma) tweeted that he would like to scale back: “The present crisis is an opportunity to reassess what is actually necessary and rebalance [in terms of meetings].”
Travel to meetings is often unpleasant, said others.
Chris Palatucci, life sciences executive recruiter, Coulter Partners, Boston, tweeted (@LifeSciRcruitr): “I will die a happy man if I never get on another plane. Glorified bus travel.” He also believes that once the coronavirus crisis is over, its “silver lining” will be the realization that “40% of all meetings are unnecessary.”
Many professionals have welcomed the announcements that major conferences have been canceled and will be conducted virtually.
The latest change is from the American Society of Clinical Oncology (ASCO), whose annual meeting was to be held in Chicago at the end of May but will now be held online.
Virtual ASCO will be more manageable – and comfy, said Fumiko Ladd Chino, MD, radiation oncologist, Memorial Sloan Kettering Cancer Center, New York City.
She (@fumikochino) explained why in a recent tweet: “1) I will be finally able to see ALL OF THE PRESENTATIONS I wanted to see instead of wandering around feeling overwhelmed. 2) I will be able to FOCUS on the presentations and not searching for a power outlet. 3) PAJAMAS.”
Virtual meetings already beat real meetings, added Adriana Scheliga, MD, hematologist-oncologist, Brazilian National Cancer Institute (@linfopedia): “I’ve been saying this for a while. For me the best ASCO Meetings, for example, are the “virtual meetings!”
However, meetings in place are also very much about professional community and mutual support, reminds Susan E. Sedory, MA, executive director, Society of Interventional Radiology, which canceled its meeting March 6 in a multifaceted process described by Medscape Medical News.
Is This the Time to Evaluate Meetings?
Coming up soon is the first major conference to go virtual after being canceled – the American College of Cardiology (ACC), which has been one of the top 20 largest meetings in the United States by attendance.
This meeting, which was to have taken place in Chicago on March 28–30, will now occur online on those days. The ACC says it will stream all “live” sessions on demand and provide access to additional videos, abstracts, and slides for at least 90 days after the meeting. And it will be free to anyone with an Internet connection.
Medical meetings in distant locales may bounce back, as they have grown into a very big business. ASCO is illustrative.
The group’s first scientific annual meeting was held in 1965 in Philadelphia, with about 70 members and invited guests in attendance. Fast forward 50-plus years to 2019: there were 42,500 attendees, a 4.4% increase from 2018. Notably, the top countries in attendance in 2019 were the United States and China.
Not everyone is happy that canceled meetings are being held online in the middle of a pandemic.
“In a COVID-19 world, the brain cannot focus on nonviral topics,” said commentator John Mandrola, MD, Baptist Health, Louisville, Kentucky, in his regular column for Medscape Cardiology/theheart.org.
The virtual ACC meeting should be canceled or delayed – to mirror what is happening in the world, he argues. “In hospitals, we have postponed the elective to make room for the coming surge. Shouldn’t ACC do the same? After the crisis passes, we can have a virtual meeting with a proper discussion of the science,” he writes.
But #MedTwitter, with its collective constructive criticism of medical meetings, is perhaps proof that the brain can function – and arrive at clarity – when under pandemic duress.
“Am I the only one experiencing a certain relief at the cancellation of multiple trips and meetings, and vowing to let this revelation affect my decision making in the future,” tweeted Steven Joffe, MD, MPH, University of Pennsylvania, Philadelphia (@Steve Joffe).
Louise Perkins King, MD, a bioethicist at Harvard Medical School, responded to Joffe. Hoping not to “belittle” the suffering from the COVID-19 pandemic, she (@louise_p_king) addressed her healthcare colleagues: “...there is potential for us all to learn what is essential travel and burden and what is not from this. I hope it leads to lasting change.”
This article first appeared on Medscape.com.
As most 2020 medical conferences have, one by one, been canceled or rescheduled as virtual meetings in the time of a pandemic, some physicians and other healthcare professionals are wondering if this is the year that will change the scene forever.
Amid the choruses of resignation (“Unfortunately, it’s the right thing to do.”) and optimism (“See you next year!”), there have been plenty of voices describing another broad sentiment – that all was not well with medical meetings even before the coronavirus.
One dominant criticism is that there are too many meetings.
Indeed, there are many, many meetings. During 2005–2015, there were 30,000-plus medical meetings in the United States, according to a report from the Healthcare Convention and Exhibitors Association.
Most of those are of little value, tweeted Dhruv Khullar, MD, an internist at Weill Cornell Medicine, New York City (@DhruvKhullar): “One possible consequence of cancelling so many meetings due to #COVID19 is that we realize we probably don’t need most of them.”
The tweet was liked 1.9K times, which is high for a medical post. Comments were mostly in agreement, with some skepticism.
Michaela West, MD, PhD, a surgeon at North Memorial Health, Minneapolis, Minnesota, responded (@MichaelaWst): “Agree. COVID-19 may forever change our perspective regarding medical professional meetings.”
Nwando Olayiwola, MD, chair of family medicine, Ohio State University, Columbus, strongly agreed (@DrNwando): “This is the tweet I wish I tweeted.”
However, Kelly Swords, MD, MPH, urologist, University of California, San Diego, in a dissenting opinion, stated the obvious (@k_dagger): “Except there is no substitute for human interaction.”
Worth the Effort?
The cancellation of medical meetings has given those who regularly attend an opportunity to reassess their value and to question the worth of the effort involved in attending in person.
David Steensma, MD, hematologist-oncologist, Harvard Medical School, Boston, (@DavidSteensma) tweeted that he would like to scale back: “The present crisis is an opportunity to reassess what is actually necessary and rebalance [in terms of meetings].”
Travel to meetings is often unpleasant, said others.
Chris Palatucci, life sciences executive recruiter, Coulter Partners, Boston, tweeted (@LifeSciRcruitr): “I will die a happy man if I never get on another plane. Glorified bus travel.” He also believes that once the coronavirus crisis is over, its “silver lining” will be the realization that “40% of all meetings are unnecessary.”
Many professionals have welcomed the announcements that major conferences have been canceled and will be conducted virtually.
The latest change is from the American Society of Clinical Oncology (ASCO), whose annual meeting was to be held in Chicago at the end of May but will now be held online.
Virtual ASCO will be more manageable – and comfy, said Fumiko Ladd Chino, MD, radiation oncologist, Memorial Sloan Kettering Cancer Center, New York City.
She (@fumikochino) explained why in a recent tweet: “1) I will be finally able to see ALL OF THE PRESENTATIONS I wanted to see instead of wandering around feeling overwhelmed. 2) I will be able to FOCUS on the presentations and not searching for a power outlet. 3) PAJAMAS.”
Virtual meetings already beat real meetings, added Adriana Scheliga, MD, hematologist-oncologist, Brazilian National Cancer Institute (@linfopedia): “I’ve been saying this for a while. For me the best ASCO Meetings, for example, are the “virtual meetings!”
However, meetings in place are also very much about professional community and mutual support, reminds Susan E. Sedory, MA, executive director, Society of Interventional Radiology, which canceled its meeting March 6 in a multifaceted process described by Medscape Medical News.
Is This the Time to Evaluate Meetings?
Coming up soon is the first major conference to go virtual after being canceled – the American College of Cardiology (ACC), which has been one of the top 20 largest meetings in the United States by attendance.
This meeting, which was to have taken place in Chicago on March 28–30, will now occur online on those days. The ACC says it will stream all “live” sessions on demand and provide access to additional videos, abstracts, and slides for at least 90 days after the meeting. And it will be free to anyone with an Internet connection.
Medical meetings in distant locales may bounce back, as they have grown into a very big business. ASCO is illustrative.
The group’s first scientific annual meeting was held in 1965 in Philadelphia, with about 70 members and invited guests in attendance. Fast forward 50-plus years to 2019: there were 42,500 attendees, a 4.4% increase from 2018. Notably, the top countries in attendance in 2019 were the United States and China.
Not everyone is happy that canceled meetings are being held online in the middle of a pandemic.
“In a COVID-19 world, the brain cannot focus on nonviral topics,” said commentator John Mandrola, MD, Baptist Health, Louisville, Kentucky, in his regular column for Medscape Cardiology/theheart.org.
The virtual ACC meeting should be canceled or delayed – to mirror what is happening in the world, he argues. “In hospitals, we have postponed the elective to make room for the coming surge. Shouldn’t ACC do the same? After the crisis passes, we can have a virtual meeting with a proper discussion of the science,” he writes.
But #MedTwitter, with its collective constructive criticism of medical meetings, is perhaps proof that the brain can function – and arrive at clarity – when under pandemic duress.
“Am I the only one experiencing a certain relief at the cancellation of multiple trips and meetings, and vowing to let this revelation affect my decision making in the future,” tweeted Steven Joffe, MD, MPH, University of Pennsylvania, Philadelphia (@Steve Joffe).
Louise Perkins King, MD, a bioethicist at Harvard Medical School, responded to Joffe. Hoping not to “belittle” the suffering from the COVID-19 pandemic, she (@louise_p_king) addressed her healthcare colleagues: “...there is potential for us all to learn what is essential travel and burden and what is not from this. I hope it leads to lasting change.”
This article first appeared on Medscape.com.
As most 2020 medical conferences have, one by one, been canceled or rescheduled as virtual meetings in the time of a pandemic, some physicians and other healthcare professionals are wondering if this is the year that will change the scene forever.
Amid the choruses of resignation (“Unfortunately, it’s the right thing to do.”) and optimism (“See you next year!”), there have been plenty of voices describing another broad sentiment – that all was not well with medical meetings even before the coronavirus.
One dominant criticism is that there are too many meetings.
Indeed, there are many, many meetings. During 2005–2015, there were 30,000-plus medical meetings in the United States, according to a report from the Healthcare Convention and Exhibitors Association.
Most of those are of little value, tweeted Dhruv Khullar, MD, an internist at Weill Cornell Medicine, New York City (@DhruvKhullar): “One possible consequence of cancelling so many meetings due to #COVID19 is that we realize we probably don’t need most of them.”
The tweet was liked 1.9K times, which is high for a medical post. Comments were mostly in agreement, with some skepticism.
Michaela West, MD, PhD, a surgeon at North Memorial Health, Minneapolis, Minnesota, responded (@MichaelaWst): “Agree. COVID-19 may forever change our perspective regarding medical professional meetings.”
Nwando Olayiwola, MD, chair of family medicine, Ohio State University, Columbus, strongly agreed (@DrNwando): “This is the tweet I wish I tweeted.”
However, Kelly Swords, MD, MPH, urologist, University of California, San Diego, in a dissenting opinion, stated the obvious (@k_dagger): “Except there is no substitute for human interaction.”
Worth the Effort?
The cancellation of medical meetings has given those who regularly attend an opportunity to reassess their value and to question the worth of the effort involved in attending in person.
David Steensma, MD, hematologist-oncologist, Harvard Medical School, Boston, (@DavidSteensma) tweeted that he would like to scale back: “The present crisis is an opportunity to reassess what is actually necessary and rebalance [in terms of meetings].”
Travel to meetings is often unpleasant, said others.
Chris Palatucci, life sciences executive recruiter, Coulter Partners, Boston, tweeted (@LifeSciRcruitr): “I will die a happy man if I never get on another plane. Glorified bus travel.” He also believes that once the coronavirus crisis is over, its “silver lining” will be the realization that “40% of all meetings are unnecessary.”
Many professionals have welcomed the announcements that major conferences have been canceled and will be conducted virtually.
The latest change is from the American Society of Clinical Oncology (ASCO), whose annual meeting was to be held in Chicago at the end of May but will now be held online.
Virtual ASCO will be more manageable – and comfy, said Fumiko Ladd Chino, MD, radiation oncologist, Memorial Sloan Kettering Cancer Center, New York City.
She (@fumikochino) explained why in a recent tweet: “1) I will be finally able to see ALL OF THE PRESENTATIONS I wanted to see instead of wandering around feeling overwhelmed. 2) I will be able to FOCUS on the presentations and not searching for a power outlet. 3) PAJAMAS.”
Virtual meetings already beat real meetings, added Adriana Scheliga, MD, hematologist-oncologist, Brazilian National Cancer Institute (@linfopedia): “I’ve been saying this for a while. For me the best ASCO Meetings, for example, are the “virtual meetings!”
However, meetings in place are also very much about professional community and mutual support, reminds Susan E. Sedory, MA, executive director, Society of Interventional Radiology, which canceled its meeting March 6 in a multifaceted process described by Medscape Medical News.
Is This the Time to Evaluate Meetings?
Coming up soon is the first major conference to go virtual after being canceled – the American College of Cardiology (ACC), which has been one of the top 20 largest meetings in the United States by attendance.
This meeting, which was to have taken place in Chicago on March 28–30, will now occur online on those days. The ACC says it will stream all “live” sessions on demand and provide access to additional videos, abstracts, and slides for at least 90 days after the meeting. And it will be free to anyone with an Internet connection.
Medical meetings in distant locales may bounce back, as they have grown into a very big business. ASCO is illustrative.
The group’s first scientific annual meeting was held in 1965 in Philadelphia, with about 70 members and invited guests in attendance. Fast forward 50-plus years to 2019: there were 42,500 attendees, a 4.4% increase from 2018. Notably, the top countries in attendance in 2019 were the United States and China.
Not everyone is happy that canceled meetings are being held online in the middle of a pandemic.
“In a COVID-19 world, the brain cannot focus on nonviral topics,” said commentator John Mandrola, MD, Baptist Health, Louisville, Kentucky, in his regular column for Medscape Cardiology/theheart.org.
The virtual ACC meeting should be canceled or delayed – to mirror what is happening in the world, he argues. “In hospitals, we have postponed the elective to make room for the coming surge. Shouldn’t ACC do the same? After the crisis passes, we can have a virtual meeting with a proper discussion of the science,” he writes.
But #MedTwitter, with its collective constructive criticism of medical meetings, is perhaps proof that the brain can function – and arrive at clarity – when under pandemic duress.
“Am I the only one experiencing a certain relief at the cancellation of multiple trips and meetings, and vowing to let this revelation affect my decision making in the future,” tweeted Steven Joffe, MD, MPH, University of Pennsylvania, Philadelphia (@Steve Joffe).
Louise Perkins King, MD, a bioethicist at Harvard Medical School, responded to Joffe. Hoping not to “belittle” the suffering from the COVID-19 pandemic, she (@louise_p_king) addressed her healthcare colleagues: “...there is potential for us all to learn what is essential travel and burden and what is not from this. I hope it leads to lasting change.”
This article first appeared on Medscape.com.
The power and promise of person-generated health data (Part II)
In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals.
Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
Identifying a disease early
One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.
In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.1
A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
Leading to better health outcomes
The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.2
This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.
Presenting new challenges
While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.3
The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.
This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.
Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.4 With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events. Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.5 This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.
Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.
Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.
References
1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.
2. The Heartline Study. https://www.heartline.com.
3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.
4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.
5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.
In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals.
Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
Identifying a disease early
One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.
In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.1
A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
Leading to better health outcomes
The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.2
This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.
Presenting new challenges
While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.3
The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.
This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.
Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.4 With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events. Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.5 This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.
Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.
Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.
References
1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.
2. The Heartline Study. https://www.heartline.com.
3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.
4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.
5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.
In Part I of our discussion we introduced the concept of person-generated health data (PGHD), defined as wellness and/or health-related data created, recorded, or gathered by individuals.
Such rich, longitudinal information is now being used in combination with traditional clinical information to predict, diagnose, and formulate treatment plans for diseases, as well as understand the safety and effectiveness of medical interventions.
Identifying a disease early
One novel example of digital technologies being used for early identification of disease was a promising 2019 study by Eli Lilly (in collaboration with Apple and Evidation Health) called the Lilly Exploratory Digital Assessment Study.
In this study, the feasibility of using PGHD for identifying physiological and behavioral signatures of cognitive impairment was examined for the purpose of seeking new methods to detect mild cognitive impairment (MCI) in a timely and cost-effective manner. The study enrolled 31 study participants with cognitive impairment and 82 without cognitive impairment. It used consumer-grade sensor technologies (the iPhone, Apple Watch, iPad, and Beddit sleep monitor) to continuously and unobtrusively collect data. Among the information the researchers collected were interaction with the phone keyboard, accelerometer data from the Apple Watch, volume of messages sent/received, and sleep cycles.1
A total of 16 terabytes of data were collected over the course of 12 weeks. Data were organized into a behaviorgram (See Figure 1) that gives a holistic picture of a day in a patient’s life. A machine learning model was used to distinguish between behaviorgrams of symptomatic versus healthy controls, identifying typing speed, circadian rhythm shifts, and reliance on helper apps, among other things, as differentiating cognitively impaired from healthy controls. These behaviorgrams may someday serve as “fingerprints” of different diseases, with specific diseases displaying predictable patterns. In the near future, digital measures like the ones investigated in this study are likely to be used to help clinicians predict and diagnose disease, as well as to better understand disease progression and treatment response.
Leading to better health outcomes
The potential of PGHD to detect diseases early and lead to better health outcomes is being investigated in the Heartline study, a collaboration between Johnson & Johnson and Apple, which is supported by Evidation.2
This study aims to enroll 150,000 adults age 65 years and over to analyze the impact of Apple Watch–based early detection of irregular heart rhythms consistent with atrial fibrillation (AFib). The researchers’ hypothesis is that jointly detecting atrial fibrillation early and providing cardiovascular health programs to new AFib patients, will lead to patients being treated by a medical provider for AFib that otherwise would not have been detected. This, in turn, would lead to these AFib patients decreasing their risks of stroke and other serious cardiovascular events, including death, the study authors speculated.
Presenting new challenges
While PGHD has the potential to help people, it also presents new challenges. It is highly sensitive and personal – it can be as identifying as DNA.3
The vast amount of data that PGHD can collect from interaction with consumer wearable devices poses serious privacy risks if done improperly. To address those risks, companies like Evidation have built in protections. Evidation has an app, Achievement, that has enlisted a connected population of more than 3.5 million members who earn rewards for performing health-related actions, as tracked by wearables devices and apps. Through the Achievement app (See Figure 2.), members are provided opportunities to join research studies. As part of these studies, data collected from sensors and apps is used by permission of the member so that it is clear how their data are contributing to specific research questions or use cases.
This is a collaborative model of data collection built upon trust and permission and is substantially different than the collection of data from electronic health records (EHRs) – which is typically aggregated, deidentified, and commercialized, often without the patients’ knowledge or consent. Stringent protections, explicit permission, and transparency are absolutely imperative until privacy frameworks for data outside of HIPAA regulation catches up and protects patients from discrimination and unintended uses of their data.
Large connected cohorts can help advance our understanding of public health. In one study run on Achievement during the 2017-2018 flu season, a survey was sent to the Achievement population every week asking about symptoms of influenza-like illness and requesting permission to access historical data from their wearable around the influenza-like illness event.4 With the data, it was possible to analyze patterns of activity, sleep, and resting heart rate change around flu events. Resting heart rate, in particular, is shown to increase during fever and at the population level. In fact, through the use of PGHD, it is possible to use the fraction of people with resting heart rate above their usual baseline as a proxy to quantify the number of infected people in a region.5 This resting heart rate–informed flu surveillance method, if refined to increased accuracy, can work in near real time. This means it may be able detect influenza outbreaks days earlier than current epidemiological methods.
Health data generated by connected populations are in the early stages of development. It is clear that it will yield novel insights into health and disease. Only time will tell if it will be able to help clinicians and patients better predict, diagnose, and formulate treatment plans for disease.
Neil Skolnik, M.D. is a professor of family and community medicine at Sidney Kimmel Medical College, Thomas Jefferson University, and associate director of the Family Medicine Residency Program at Abington Jefferson Health. Luca Foschini PhD, is co-founder & chief data scientist at Evidation Health. Bray Patrick-Lake, MFS, is a patient thought leader and director of strategic partnerships at Evidation Health.
References
1. Chen R et al. Developing measures of cognitive impairment in the real world from consumer-grade multimodal sensor streams. KDD ’19. August 4–8, 2019 Aug 4-8.
2. The Heartline Study. https://www.heartline.com.
3. Foschini L. Privacy of Wearable and Sensors Data (or, the Lack Thereof?). Data Driven Investor, Medium. 2019.
4. Bradshaw B et al. Influenza surveillance using wearable mobile health devices. Online J Public Health Inform. 2019;11(1):e249.
5. Radin JM et al. Harnessing wearable device data to improve state-level real-time surveillance of influenza-like illness in the USA: a population-based study. Lancet Digital Health. 2020. doi: 10.1016/S2589-7500(19)30222-5.
EULAR cancels June congress, will hold virtual meeting instead
The European League Against Rheumatism has canceled its annual congress scheduled for June 3-6, 2020, in Frankfurt, Germany, and will instead hold a virtual meeting around the same time frame, according to a message from the organization’s president, Iain McInnes, MD, PhD.
“As a scientific medical society, it is our duty to ensure that our medical and health professional participants are available at the forefront of patient care. We are also concerned that bringing our RMD [rheumatic and musculoskeletal disease] patient delegates into a large meeting venue would be extremely unwise at this time,” Dr. McInnes wrote.
While the details of the virtual congress experience have yet to be worked out, Dr. McInnes said that its offerings “will be accessible on demand over a timeframe of several months,” and they “will also publish abstracts/posters online and provide registered delegates with the 1-year access to our journal, the Annals of Rheumatic Diseases.”
The EULAR president also asked for patience as the details of the virtual congress are determined. “We ask you to be patient for a little while longer to give us the time to develop clear answers to all your questions. Our volunteers and staff in the EULAR Office are currently working hard to develop the best possible solutions for this new scenario.”
The European League Against Rheumatism has canceled its annual congress scheduled for June 3-6, 2020, in Frankfurt, Germany, and will instead hold a virtual meeting around the same time frame, according to a message from the organization’s president, Iain McInnes, MD, PhD.
“As a scientific medical society, it is our duty to ensure that our medical and health professional participants are available at the forefront of patient care. We are also concerned that bringing our RMD [rheumatic and musculoskeletal disease] patient delegates into a large meeting venue would be extremely unwise at this time,” Dr. McInnes wrote.
While the details of the virtual congress experience have yet to be worked out, Dr. McInnes said that its offerings “will be accessible on demand over a timeframe of several months,” and they “will also publish abstracts/posters online and provide registered delegates with the 1-year access to our journal, the Annals of Rheumatic Diseases.”
The EULAR president also asked for patience as the details of the virtual congress are determined. “We ask you to be patient for a little while longer to give us the time to develop clear answers to all your questions. Our volunteers and staff in the EULAR Office are currently working hard to develop the best possible solutions for this new scenario.”
The European League Against Rheumatism has canceled its annual congress scheduled for June 3-6, 2020, in Frankfurt, Germany, and will instead hold a virtual meeting around the same time frame, according to a message from the organization’s president, Iain McInnes, MD, PhD.
“As a scientific medical society, it is our duty to ensure that our medical and health professional participants are available at the forefront of patient care. We are also concerned that bringing our RMD [rheumatic and musculoskeletal disease] patient delegates into a large meeting venue would be extremely unwise at this time,” Dr. McInnes wrote.
While the details of the virtual congress experience have yet to be worked out, Dr. McInnes said that its offerings “will be accessible on demand over a timeframe of several months,” and they “will also publish abstracts/posters online and provide registered delegates with the 1-year access to our journal, the Annals of Rheumatic Diseases.”
The EULAR president also asked for patience as the details of the virtual congress are determined. “We ask you to be patient for a little while longer to give us the time to develop clear answers to all your questions. Our volunteers and staff in the EULAR Office are currently working hard to develop the best possible solutions for this new scenario.”
Novel drugs approved in 2019
In 2019, the Food and Drug Administration approved 42 drugs, 6 of which will not be discussed here because of space limitations: recarbrio, a three-drug combination, containing imipenem, cilastatin, and relebactam; polatuzumab (Polivy) combined with bendamustine and a rituximab product; pretomanid combined with bedaquiline and linezolid; romosozumab (Evenity) for postmenopausal women; and alpelisib (Piqray) for postmenopausal women. In addition, darolutamide (Nubeqa) will not be included because it is indicated for the treatment of patients with prostate cancer. The remaining 36 agents are listed alphabetically below with the trade names in parentheses.
The molecular weights (if available), rounded to the nearest whole number, are shown in parentheses.
Air polymer-type a intrauterine foam (ExEm Foam), an ultrasound contrast agent, is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. Animal studies have not been conducted, and the agent is contraindicated in pregnancy.
Afamelanotide implant (Scenesse) (1,647) is a melanocortin 1 receptor agonist that is indicated to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. The drug caused no embryofetal toxicity in two species of rats. The molecular weight suggests that it will not cross the placenta, at least early in pregnancy.
Alpelisib (Piqray) (441) is a kinase inhibitor that is combined with fulvestrant for the treatment of advanced breast cancer in women and men. The molecular weight suggests that it can cross the human placenta. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Bremelanotide (Vyleesi) (1,025) is indicated for the treatment of premenopausal women with hypoactive sexual disorder. The drug caused fetal harm in dogs and mice. If a pregnant woman is exposed to the drug, health care providers are encouraged to call the VYLEESI Pregnancy Exposure Registry at 877-411-2510.
Brolucizumab (Beovu) (26,000) is a human vascular endothelial growth factor that is indicated for the treatment of neovascular age-related macular degeneration. In animals, it caused malformations, embryofetal resorption, and decreased fetal weight. Other adverse effects were follicular development, corpus luteum function, and fertility.
Caplacizumab (Cablivi) (28,000) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenia purpura, in combination with plasma exchange and immunosuppressive therapy. If used in pregnancy, there is a risk of hemorrhage in the mother and fetus. In guinea pigs given intramuscular doses of the drug, there was no evidence of adverse developmental outcomes.
Cefiderocol (Fetroja) (3,044) is an IV cephalosporin antibiotic indicated for the treatment of urinary tract infections, including pyelonephritis. The manufacturer states that it should be used in patients 18 years of age or older who have limited or no alternative treatment options. Consistent with other cephalosporins, no developmental adverse effects were observed in rats and mice.
Cenobamate (Xcopri) (268) is indicated for the treatment of partial-onset seizures in adults. In pregnant animals given the drug, there was increased embryo-fetal mortality, decreased fetal and offspring body weight, and neurobehavioral and reproductive impairment in offspring. If a pregnant woman receives this drug, encourage her to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll-free number 1-888-233-2334.
Crizanlizumab (Adakveo) (146,000) is indicated to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. In monkeys given doses slightly higher than those given to humans, there was increased fetal loss (abortions/stillbirths).
Entrectinib (Rozlytrek) (561) is a kinase inhibitor indicated for the treatment of cancer. The drug was teratogenic in rats. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Erdafitinib (Balversa) (447), a kinase inhibitor, is indicated for the treatment of locally advanced or metastatic urothelial carcinoma. In rats given doses during organogenesis with maternal exposures less than human exposures, the drug was teratogenic and caused embryofetal death. The manufacturer states that women of reproductive potential should use effective contraception during treatment and for 1 month after the last dose. The same advice was provided for male patients with female partners of reproductive potential. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Fedratinib (Inrebic) (616), a kinase inhibitor, is indicated for patients with intermediate-2 or high-risk primary or secondary myelofibrosis. The drug was teratogenic in rats when doses that were about 0.1 times the human exposure based on AUC (area under the curve) at the recommended daily dose during organogenesis. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Fluorodopa f18 (214) is a radioactive diagnostic agent. It is indicated for use in positron emission tomography to visualize dopaminergic nerve terminals in the striatum for evaluation of adult patients with suspected parkinsonian syndromes. The potential for adverse pregnant outcomes is based on the radiation dose and the gestational timing of exposure.
Givosiran sodium (Givlaari) (17,2460) is an aminolevulinate synthase 1-directed small interfering RNA given subcutaneously. It is indicated for the treatment of adults with acute hepatic porphyria. Doses less than 10 times the human dose in rats and rabbits produced maternal toxicity. In rats there was increased postimplantation loss, and in rats there was skeletal variation (incomplete ossification of pubes).
Golodirsen (Vyondys 53) (8,647) is indicated for the treatment of Duchenne muscular dystrophy given intravenously. There are no human or animal data available to assess the use of this drug during pregnancy.
Istradefylline (Nourianz) (384) is an adenosine receptor antagonist given orally. It is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. In pregnant rats and rabbits, the drug was related to teratogenicity, embryo-fetal and offspring mortality, and growth deficits at clinically relevant exposures.
Lasmiditan (Reyvow) (436), a serotonin receptor agonist, is indicated for acute treatment of migraine with or without aura. In animals, the drug caused increased incidences of fetal defects, increased embryo-fetal and offspring mortality, and decreased fetal body weight at maternal exposures less than (rabbits) or greater than (rat) those observed clinically.
Lefamulin (Xenleta) (568) is an antibacterial agent available for oral and IV administration. They are indicated for the treatment of community-acquired bacterial pneumonia. The drug was teratogenic in rats at systemic exposures lower than those in humans, an increased incidence of post-implantation fetal loss and stillbirths, and decreased fetal body weights and ossification. There was also an apparent delay in sexual maturation in rats.
Luspatercept (Reblozyl) (76,000) is given subcutaneously for the treatment of anemia in patients with beta thalassemia who require regular red blood cell transfusions. In rats and rabbits, the drug cause increased embryo-fetal mortality, alteration to growth, and structural defects at exposures (based on AUC) that were about 13 times (rats) and 18 times (rabbits) the maximum recommended human dose.
Pexidartinib (Turalio) (454) is an oral kinase inhibitor that is indicated for the treatment of symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable with surgery. In rats and rabbits, the drug caused malformations, increased post-implantation loss, and abortion at exposures nearly equal to the human exposure. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Pitolisant HCl (Wakix) (296) is an histamine-3 receptor antagonist/inverse agonist indicated for the treatment of excessive daytime sleepiness in patients with narcolepsy. The drug has caused maternal and embryofetal toxicity in rats and rabbits at doses greater than and equal to 13 times and greater than 4 times the maximum human dose, respectively. The manufacturer has a pregnancy exposure registry that patients can contact at 1-800-833-7460.
Prabotulinum toxin A (Jeuveau) (900,000) is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity. The drug caused no adverse embryo-fetal in rats with doses up to 12 times the human dose.
Risankizumab-rzaa (Skyrizi) (molecular weight unknown), an interleukin-23 antagonist, is used for the treatment of moderate-to-severe plaque psoriasis. In pregnant monkeys, doses that were 20 times the maximum human dose increased fetal/infant loss.
Selinexor (Xpovio) (443) is an oral nuclear export inhibitor given in combination with dexamethasone for the treatment of relapsed or refractory myeloma. At doses lower than those used clinically, the drug caused structural abnormalities and alterations to growth in fetal rats.
Siponimod (Mayzent) (1,149) is an oral sphingosine 1-phosphate receptor modulator. It is indicated for the treatment of relapsing forms of multiple sclerosis. At low doses, the drug caused embryotoxicity and fetotoxicity in rats and rabbits including embryofetal deaths and abortions. The drug was teratogenic in both species.
Solriamfetol (Sunosi) (231) is an oral dopamine and norepinephrine reuptake inhibitor that is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. The drug caused maternal and fetal toxicities in rats and rabbits and was teratogenic. The manufacturer has a pregnancy exposure registry to monitor pregnancy outcomes. Health care providers or patients can enroll in the program by calling 1-877-283-6220 or contacting the company.
Tafamidis meglumine (Vyndaqel) (503) and tafamidis (Vyndamax) (308) are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis to reduce cardiovascular mortality and cardiovascular-related hospitalization. In rabbits and rats, use of the drugs during pregnancy caused birth defects, embryo-fetal mortality, and fetal body weight reduction. Limited available data with Vyndaqel use in human pregnancy at a dose of 20 mg/day have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see package insert).
Tenapanor (Ibsrela) (1,218) is indicated for the treatment of irritable bowel syndrome with constipation. The drug is minimally absorbed systemically, with plasma concentrations below the limit of quantification. No adverse maternal or fetal outcomes in rats or rabbits were observed. As reported by the manufacturer, in a small number of pregnant women, no drug-induced adverse maternal or fetal outcomes were identified.
Triclabendazole (Egaten) (360), an oral anthelmintic, is indicated for the treatment of fascioliasis. The drug was not teratogenic in mice and rabbits.
Trifarotene (Aklief) (460) cream is a retinoid that is indicated for the topical treatment of acne vulgaris. Animal data was related to oral retinoids and it not applicable to this agent. The manufacturer reported that available data from the use of the cream in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Upadacitinib (Rinvoq) (389) is an oral Janus inhibitor. It is indicated for the treatment of moderate to severe active rheumatoid arthritis in patients who have had an inadequate response or intolerance to methotrexate. The drug caused increases in fetal malformations when given to rats and rabbits during organogenesis.
Voxelotor (Oxbryta) (337) is an oral hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease. In rats and rabbits, there was no evidence of adverse developmental outcomes.
Zanubrutinib (Brukinsa) (472), an oral kinase inhibitor, is indicated for the treatment of mantle cell lymphoma. The drug caused embryofetal toxicity in pregnant rats, including malformations. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Breastfeeding
Brexanolone (Zulresso) (319) is indicated for the treatment of postpartum depression. It is given as a continuous IV infusion over 60 hours. The drug, at exposures close to those seen in humans, did not cause structural defects in rabbits and rats, but did cause fetal toxicity. Because patients are at risk of excessive sedation or sudden loss of consciousness when receiving the drug, it is only available through a restricted program called the ZULRESSO REMS. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 844-405-6185. To obtain a list of health care facilities enrolled in the program call 844-472-4379.
Nearly all of the above drugs will cross into a woman’s colostrum during the first 48 hours post partum. These amounts should be very small, but not breastfeeding is the best choice.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
In 2019, the Food and Drug Administration approved 42 drugs, 6 of which will not be discussed here because of space limitations: recarbrio, a three-drug combination, containing imipenem, cilastatin, and relebactam; polatuzumab (Polivy) combined with bendamustine and a rituximab product; pretomanid combined with bedaquiline and linezolid; romosozumab (Evenity) for postmenopausal women; and alpelisib (Piqray) for postmenopausal women. In addition, darolutamide (Nubeqa) will not be included because it is indicated for the treatment of patients with prostate cancer. The remaining 36 agents are listed alphabetically below with the trade names in parentheses.
The molecular weights (if available), rounded to the nearest whole number, are shown in parentheses.
Air polymer-type a intrauterine foam (ExEm Foam), an ultrasound contrast agent, is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. Animal studies have not been conducted, and the agent is contraindicated in pregnancy.
Afamelanotide implant (Scenesse) (1,647) is a melanocortin 1 receptor agonist that is indicated to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. The drug caused no embryofetal toxicity in two species of rats. The molecular weight suggests that it will not cross the placenta, at least early in pregnancy.
Alpelisib (Piqray) (441) is a kinase inhibitor that is combined with fulvestrant for the treatment of advanced breast cancer in women and men. The molecular weight suggests that it can cross the human placenta. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Bremelanotide (Vyleesi) (1,025) is indicated for the treatment of premenopausal women with hypoactive sexual disorder. The drug caused fetal harm in dogs and mice. If a pregnant woman is exposed to the drug, health care providers are encouraged to call the VYLEESI Pregnancy Exposure Registry at 877-411-2510.
Brolucizumab (Beovu) (26,000) is a human vascular endothelial growth factor that is indicated for the treatment of neovascular age-related macular degeneration. In animals, it caused malformations, embryofetal resorption, and decreased fetal weight. Other adverse effects were follicular development, corpus luteum function, and fertility.
Caplacizumab (Cablivi) (28,000) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenia purpura, in combination with plasma exchange and immunosuppressive therapy. If used in pregnancy, there is a risk of hemorrhage in the mother and fetus. In guinea pigs given intramuscular doses of the drug, there was no evidence of adverse developmental outcomes.
Cefiderocol (Fetroja) (3,044) is an IV cephalosporin antibiotic indicated for the treatment of urinary tract infections, including pyelonephritis. The manufacturer states that it should be used in patients 18 years of age or older who have limited or no alternative treatment options. Consistent with other cephalosporins, no developmental adverse effects were observed in rats and mice.
Cenobamate (Xcopri) (268) is indicated for the treatment of partial-onset seizures in adults. In pregnant animals given the drug, there was increased embryo-fetal mortality, decreased fetal and offspring body weight, and neurobehavioral and reproductive impairment in offspring. If a pregnant woman receives this drug, encourage her to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll-free number 1-888-233-2334.
Crizanlizumab (Adakveo) (146,000) is indicated to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. In monkeys given doses slightly higher than those given to humans, there was increased fetal loss (abortions/stillbirths).
Entrectinib (Rozlytrek) (561) is a kinase inhibitor indicated for the treatment of cancer. The drug was teratogenic in rats. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Erdafitinib (Balversa) (447), a kinase inhibitor, is indicated for the treatment of locally advanced or metastatic urothelial carcinoma. In rats given doses during organogenesis with maternal exposures less than human exposures, the drug was teratogenic and caused embryofetal death. The manufacturer states that women of reproductive potential should use effective contraception during treatment and for 1 month after the last dose. The same advice was provided for male patients with female partners of reproductive potential. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Fedratinib (Inrebic) (616), a kinase inhibitor, is indicated for patients with intermediate-2 or high-risk primary or secondary myelofibrosis. The drug was teratogenic in rats when doses that were about 0.1 times the human exposure based on AUC (area under the curve) at the recommended daily dose during organogenesis. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Fluorodopa f18 (214) is a radioactive diagnostic agent. It is indicated for use in positron emission tomography to visualize dopaminergic nerve terminals in the striatum for evaluation of adult patients with suspected parkinsonian syndromes. The potential for adverse pregnant outcomes is based on the radiation dose and the gestational timing of exposure.
Givosiran sodium (Givlaari) (17,2460) is an aminolevulinate synthase 1-directed small interfering RNA given subcutaneously. It is indicated for the treatment of adults with acute hepatic porphyria. Doses less than 10 times the human dose in rats and rabbits produced maternal toxicity. In rats there was increased postimplantation loss, and in rats there was skeletal variation (incomplete ossification of pubes).
Golodirsen (Vyondys 53) (8,647) is indicated for the treatment of Duchenne muscular dystrophy given intravenously. There are no human or animal data available to assess the use of this drug during pregnancy.
Istradefylline (Nourianz) (384) is an adenosine receptor antagonist given orally. It is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. In pregnant rats and rabbits, the drug was related to teratogenicity, embryo-fetal and offspring mortality, and growth deficits at clinically relevant exposures.
Lasmiditan (Reyvow) (436), a serotonin receptor agonist, is indicated for acute treatment of migraine with or without aura. In animals, the drug caused increased incidences of fetal defects, increased embryo-fetal and offspring mortality, and decreased fetal body weight at maternal exposures less than (rabbits) or greater than (rat) those observed clinically.
Lefamulin (Xenleta) (568) is an antibacterial agent available for oral and IV administration. They are indicated for the treatment of community-acquired bacterial pneumonia. The drug was teratogenic in rats at systemic exposures lower than those in humans, an increased incidence of post-implantation fetal loss and stillbirths, and decreased fetal body weights and ossification. There was also an apparent delay in sexual maturation in rats.
Luspatercept (Reblozyl) (76,000) is given subcutaneously for the treatment of anemia in patients with beta thalassemia who require regular red blood cell transfusions. In rats and rabbits, the drug cause increased embryo-fetal mortality, alteration to growth, and structural defects at exposures (based on AUC) that were about 13 times (rats) and 18 times (rabbits) the maximum recommended human dose.
Pexidartinib (Turalio) (454) is an oral kinase inhibitor that is indicated for the treatment of symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable with surgery. In rats and rabbits, the drug caused malformations, increased post-implantation loss, and abortion at exposures nearly equal to the human exposure. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Pitolisant HCl (Wakix) (296) is an histamine-3 receptor antagonist/inverse agonist indicated for the treatment of excessive daytime sleepiness in patients with narcolepsy. The drug has caused maternal and embryofetal toxicity in rats and rabbits at doses greater than and equal to 13 times and greater than 4 times the maximum human dose, respectively. The manufacturer has a pregnancy exposure registry that patients can contact at 1-800-833-7460.
Prabotulinum toxin A (Jeuveau) (900,000) is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity. The drug caused no adverse embryo-fetal in rats with doses up to 12 times the human dose.
Risankizumab-rzaa (Skyrizi) (molecular weight unknown), an interleukin-23 antagonist, is used for the treatment of moderate-to-severe plaque psoriasis. In pregnant monkeys, doses that were 20 times the maximum human dose increased fetal/infant loss.
Selinexor (Xpovio) (443) is an oral nuclear export inhibitor given in combination with dexamethasone for the treatment of relapsed or refractory myeloma. At doses lower than those used clinically, the drug caused structural abnormalities and alterations to growth in fetal rats.
Siponimod (Mayzent) (1,149) is an oral sphingosine 1-phosphate receptor modulator. It is indicated for the treatment of relapsing forms of multiple sclerosis. At low doses, the drug caused embryotoxicity and fetotoxicity in rats and rabbits including embryofetal deaths and abortions. The drug was teratogenic in both species.
Solriamfetol (Sunosi) (231) is an oral dopamine and norepinephrine reuptake inhibitor that is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. The drug caused maternal and fetal toxicities in rats and rabbits and was teratogenic. The manufacturer has a pregnancy exposure registry to monitor pregnancy outcomes. Health care providers or patients can enroll in the program by calling 1-877-283-6220 or contacting the company.
Tafamidis meglumine (Vyndaqel) (503) and tafamidis (Vyndamax) (308) are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis to reduce cardiovascular mortality and cardiovascular-related hospitalization. In rabbits and rats, use of the drugs during pregnancy caused birth defects, embryo-fetal mortality, and fetal body weight reduction. Limited available data with Vyndaqel use in human pregnancy at a dose of 20 mg/day have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see package insert).
Tenapanor (Ibsrela) (1,218) is indicated for the treatment of irritable bowel syndrome with constipation. The drug is minimally absorbed systemically, with plasma concentrations below the limit of quantification. No adverse maternal or fetal outcomes in rats or rabbits were observed. As reported by the manufacturer, in a small number of pregnant women, no drug-induced adverse maternal or fetal outcomes were identified.
Triclabendazole (Egaten) (360), an oral anthelmintic, is indicated for the treatment of fascioliasis. The drug was not teratogenic in mice and rabbits.
Trifarotene (Aklief) (460) cream is a retinoid that is indicated for the topical treatment of acne vulgaris. Animal data was related to oral retinoids and it not applicable to this agent. The manufacturer reported that available data from the use of the cream in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Upadacitinib (Rinvoq) (389) is an oral Janus inhibitor. It is indicated for the treatment of moderate to severe active rheumatoid arthritis in patients who have had an inadequate response or intolerance to methotrexate. The drug caused increases in fetal malformations when given to rats and rabbits during organogenesis.
Voxelotor (Oxbryta) (337) is an oral hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease. In rats and rabbits, there was no evidence of adverse developmental outcomes.
Zanubrutinib (Brukinsa) (472), an oral kinase inhibitor, is indicated for the treatment of mantle cell lymphoma. The drug caused embryofetal toxicity in pregnant rats, including malformations. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Breastfeeding
Brexanolone (Zulresso) (319) is indicated for the treatment of postpartum depression. It is given as a continuous IV infusion over 60 hours. The drug, at exposures close to those seen in humans, did not cause structural defects in rabbits and rats, but did cause fetal toxicity. Because patients are at risk of excessive sedation or sudden loss of consciousness when receiving the drug, it is only available through a restricted program called the ZULRESSO REMS. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 844-405-6185. To obtain a list of health care facilities enrolled in the program call 844-472-4379.
Nearly all of the above drugs will cross into a woman’s colostrum during the first 48 hours post partum. These amounts should be very small, but not breastfeeding is the best choice.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
In 2019, the Food and Drug Administration approved 42 drugs, 6 of which will not be discussed here because of space limitations: recarbrio, a three-drug combination, containing imipenem, cilastatin, and relebactam; polatuzumab (Polivy) combined with bendamustine and a rituximab product; pretomanid combined with bedaquiline and linezolid; romosozumab (Evenity) for postmenopausal women; and alpelisib (Piqray) for postmenopausal women. In addition, darolutamide (Nubeqa) will not be included because it is indicated for the treatment of patients with prostate cancer. The remaining 36 agents are listed alphabetically below with the trade names in parentheses.
The molecular weights (if available), rounded to the nearest whole number, are shown in parentheses.
Air polymer-type a intrauterine foam (ExEm Foam), an ultrasound contrast agent, is indicated for sonohysterosalpingography to assess fallopian tube patency in women with known or suspected infertility. Animal studies have not been conducted, and the agent is contraindicated in pregnancy.
Afamelanotide implant (Scenesse) (1,647) is a melanocortin 1 receptor agonist that is indicated to increase pain-free light exposure in adult patients with a history of phototoxic reactions from erythropoietic protoporphyria. The drug caused no embryofetal toxicity in two species of rats. The molecular weight suggests that it will not cross the placenta, at least early in pregnancy.
Alpelisib (Piqray) (441) is a kinase inhibitor that is combined with fulvestrant for the treatment of advanced breast cancer in women and men. The molecular weight suggests that it can cross the human placenta. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Bremelanotide (Vyleesi) (1,025) is indicated for the treatment of premenopausal women with hypoactive sexual disorder. The drug caused fetal harm in dogs and mice. If a pregnant woman is exposed to the drug, health care providers are encouraged to call the VYLEESI Pregnancy Exposure Registry at 877-411-2510.
Brolucizumab (Beovu) (26,000) is a human vascular endothelial growth factor that is indicated for the treatment of neovascular age-related macular degeneration. In animals, it caused malformations, embryofetal resorption, and decreased fetal weight. Other adverse effects were follicular development, corpus luteum function, and fertility.
Caplacizumab (Cablivi) (28,000) is indicated for the treatment of adult patients with acquired thrombotic thrombocytopenia purpura, in combination with plasma exchange and immunosuppressive therapy. If used in pregnancy, there is a risk of hemorrhage in the mother and fetus. In guinea pigs given intramuscular doses of the drug, there was no evidence of adverse developmental outcomes.
Cefiderocol (Fetroja) (3,044) is an IV cephalosporin antibiotic indicated for the treatment of urinary tract infections, including pyelonephritis. The manufacturer states that it should be used in patients 18 years of age or older who have limited or no alternative treatment options. Consistent with other cephalosporins, no developmental adverse effects were observed in rats and mice.
Cenobamate (Xcopri) (268) is indicated for the treatment of partial-onset seizures in adults. In pregnant animals given the drug, there was increased embryo-fetal mortality, decreased fetal and offspring body weight, and neurobehavioral and reproductive impairment in offspring. If a pregnant woman receives this drug, encourage her to enroll in the North American Antiepileptic Drug Pregnancy Registry by calling the toll-free number 1-888-233-2334.
Crizanlizumab (Adakveo) (146,000) is indicated to reduce the frequency of vaso-occlusive crises in patients with sickle cell disease. In monkeys given doses slightly higher than those given to humans, there was increased fetal loss (abortions/stillbirths).
Entrectinib (Rozlytrek) (561) is a kinase inhibitor indicated for the treatment of cancer. The drug was teratogenic in rats. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Erdafitinib (Balversa) (447), a kinase inhibitor, is indicated for the treatment of locally advanced or metastatic urothelial carcinoma. In rats given doses during organogenesis with maternal exposures less than human exposures, the drug was teratogenic and caused embryofetal death. The manufacturer states that women of reproductive potential should use effective contraception during treatment and for 1 month after the last dose. The same advice was provided for male patients with female partners of reproductive potential. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Fedratinib (Inrebic) (616), a kinase inhibitor, is indicated for patients with intermediate-2 or high-risk primary or secondary myelofibrosis. The drug was teratogenic in rats when doses that were about 0.1 times the human exposure based on AUC (area under the curve) at the recommended daily dose during organogenesis. It is contraindicated in pregnancy because it can cause embryofetal toxicity.
Fluorodopa f18 (214) is a radioactive diagnostic agent. It is indicated for use in positron emission tomography to visualize dopaminergic nerve terminals in the striatum for evaluation of adult patients with suspected parkinsonian syndromes. The potential for adverse pregnant outcomes is based on the radiation dose and the gestational timing of exposure.
Givosiran sodium (Givlaari) (17,2460) is an aminolevulinate synthase 1-directed small interfering RNA given subcutaneously. It is indicated for the treatment of adults with acute hepatic porphyria. Doses less than 10 times the human dose in rats and rabbits produced maternal toxicity. In rats there was increased postimplantation loss, and in rats there was skeletal variation (incomplete ossification of pubes).
Golodirsen (Vyondys 53) (8,647) is indicated for the treatment of Duchenne muscular dystrophy given intravenously. There are no human or animal data available to assess the use of this drug during pregnancy.
Istradefylline (Nourianz) (384) is an adenosine receptor antagonist given orally. It is indicated as adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease experiencing “off” episodes. In pregnant rats and rabbits, the drug was related to teratogenicity, embryo-fetal and offspring mortality, and growth deficits at clinically relevant exposures.
Lasmiditan (Reyvow) (436), a serotonin receptor agonist, is indicated for acute treatment of migraine with or without aura. In animals, the drug caused increased incidences of fetal defects, increased embryo-fetal and offspring mortality, and decreased fetal body weight at maternal exposures less than (rabbits) or greater than (rat) those observed clinically.
Lefamulin (Xenleta) (568) is an antibacterial agent available for oral and IV administration. They are indicated for the treatment of community-acquired bacterial pneumonia. The drug was teratogenic in rats at systemic exposures lower than those in humans, an increased incidence of post-implantation fetal loss and stillbirths, and decreased fetal body weights and ossification. There was also an apparent delay in sexual maturation in rats.
Luspatercept (Reblozyl) (76,000) is given subcutaneously for the treatment of anemia in patients with beta thalassemia who require regular red blood cell transfusions. In rats and rabbits, the drug cause increased embryo-fetal mortality, alteration to growth, and structural defects at exposures (based on AUC) that were about 13 times (rats) and 18 times (rabbits) the maximum recommended human dose.
Pexidartinib (Turalio) (454) is an oral kinase inhibitor that is indicated for the treatment of symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable with surgery. In rats and rabbits, the drug caused malformations, increased post-implantation loss, and abortion at exposures nearly equal to the human exposure. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Pitolisant HCl (Wakix) (296) is an histamine-3 receptor antagonist/inverse agonist indicated for the treatment of excessive daytime sleepiness in patients with narcolepsy. The drug has caused maternal and embryofetal toxicity in rats and rabbits at doses greater than and equal to 13 times and greater than 4 times the maximum human dose, respectively. The manufacturer has a pregnancy exposure registry that patients can contact at 1-800-833-7460.
Prabotulinum toxin A (Jeuveau) (900,000) is an acetylcholine release inhibitor and a neuromuscular blocking agent indicated for the temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity. The drug caused no adverse embryo-fetal in rats with doses up to 12 times the human dose.
Risankizumab-rzaa (Skyrizi) (molecular weight unknown), an interleukin-23 antagonist, is used for the treatment of moderate-to-severe plaque psoriasis. In pregnant monkeys, doses that were 20 times the maximum human dose increased fetal/infant loss.
Selinexor (Xpovio) (443) is an oral nuclear export inhibitor given in combination with dexamethasone for the treatment of relapsed or refractory myeloma. At doses lower than those used clinically, the drug caused structural abnormalities and alterations to growth in fetal rats.
Siponimod (Mayzent) (1,149) is an oral sphingosine 1-phosphate receptor modulator. It is indicated for the treatment of relapsing forms of multiple sclerosis. At low doses, the drug caused embryotoxicity and fetotoxicity in rats and rabbits including embryofetal deaths and abortions. The drug was teratogenic in both species.
Solriamfetol (Sunosi) (231) is an oral dopamine and norepinephrine reuptake inhibitor that is indicated to improve wakefulness in adult patients with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. The drug caused maternal and fetal toxicities in rats and rabbits and was teratogenic. The manufacturer has a pregnancy exposure registry to monitor pregnancy outcomes. Health care providers or patients can enroll in the program by calling 1-877-283-6220 or contacting the company.
Tafamidis meglumine (Vyndaqel) (503) and tafamidis (Vyndamax) (308) are indicated for the treatment of the cardiomyopathy of wild type or hereditary transthyretin-mediated amyloidosis to reduce cardiovascular mortality and cardiovascular-related hospitalization. In rabbits and rats, use of the drugs during pregnancy caused birth defects, embryo-fetal mortality, and fetal body weight reduction. Limited available data with Vyndaqel use in human pregnancy at a dose of 20 mg/day have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal or fetal outcomes (see package insert).
Tenapanor (Ibsrela) (1,218) is indicated for the treatment of irritable bowel syndrome with constipation. The drug is minimally absorbed systemically, with plasma concentrations below the limit of quantification. No adverse maternal or fetal outcomes in rats or rabbits were observed. As reported by the manufacturer, in a small number of pregnant women, no drug-induced adverse maternal or fetal outcomes were identified.
Triclabendazole (Egaten) (360), an oral anthelmintic, is indicated for the treatment of fascioliasis. The drug was not teratogenic in mice and rabbits.
Trifarotene (Aklief) (460) cream is a retinoid that is indicated for the topical treatment of acne vulgaris. Animal data was related to oral retinoids and it not applicable to this agent. The manufacturer reported that available data from the use of the cream in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.
Upadacitinib (Rinvoq) (389) is an oral Janus inhibitor. It is indicated for the treatment of moderate to severe active rheumatoid arthritis in patients who have had an inadequate response or intolerance to methotrexate. The drug caused increases in fetal malformations when given to rats and rabbits during organogenesis.
Voxelotor (Oxbryta) (337) is an oral hemoglobin S polymerization inhibitor indicated for the treatment of sickle cell disease. In rats and rabbits, there was no evidence of adverse developmental outcomes.
Zanubrutinib (Brukinsa) (472), an oral kinase inhibitor, is indicated for the treatment of mantle cell lymphoma. The drug caused embryofetal toxicity in pregnant rats, including malformations. It is contraindicated in pregnancy because it can cause embryo-fetal toxicity.
Breastfeeding
Brexanolone (Zulresso) (319) is indicated for the treatment of postpartum depression. It is given as a continuous IV infusion over 60 hours. The drug, at exposures close to those seen in humans, did not cause structural defects in rabbits and rats, but did cause fetal toxicity. Because patients are at risk of excessive sedation or sudden loss of consciousness when receiving the drug, it is only available through a restricted program called the ZULRESSO REMS. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 844-405-6185. To obtain a list of health care facilities enrolled in the program call 844-472-4379.
Nearly all of the above drugs will cross into a woman’s colostrum during the first 48 hours post partum. These amounts should be very small, but not breastfeeding is the best choice.
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.
Hormone therapy boosts body image in transgender youth
based on data from 148 individuals.
“Understanding the impact of gender-affirming hormone therapy on the mental health of transgender youth is critical given the health disparities documented in this population,” wrote Laura E. Kuper, PhD, of Children’s Health Systems of Texas, Dallas, and colleagues.
In a study published in Pediatrics, the researchers reviewed data from 148 youth aged 9-18 years who underwent gender-affirming hormone therapy in a multidisciplinary program. The average age of the patients was 15 years; 25 were receiving puberty suppression hormones only, 93 were receiving just feminizing or masculinizing hormones, and 30 were receiving both treatments.
At baseline and at approximately 1 year follow-up, all patients completed the Body Image Scale, Quick Inventory of Depressive Symptoms, and Screen for Child Anxiety Related Emotional Disorders. In addition, clinicians collected information on patients’ suicidal ideation, suicide attempts, and nonsuicidal self-injury.
Overall, the average scores on the Body Image Scale on body dissatisfaction decreased from 70 to 52, and average scores on the Quick Inventory of Depressive Symptoms decreased from 9 to 7; both were statistically significant (P less than .001), as were changes from baseline on the anxiety subscale of the Screen for Child Anxiety Related Emotional Disorders, which decreased from 32 to 29 (P less than .01). No change occurred in the average overall clinician-reported depressive symptoms.
During the follow-up period, the rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury were 38%, 5%, and 17%, respectively. Of patients who reported these experiences, the lifetime histories of suicidal ideation, suicide attempts, and nonsuicidal self-injury were 81%, 15%, and 52%, respectively.
The findings were limited by several factors including some missing data and the relatively small sample size, the researchers noted.
Nonetheless, the results suggest “that youth receiving gender-affirming hormone therapy experience meaningful short-term improvements in body dissatisfaction, and no participants discontinued feminizing or masculinizing hormone therapy.” These results support the use of such therapy, Dr. Kuper and associates wrote.
The study is important because of the need for evidence that hormones actually improve patient outcomes, said Shauna M. Lawlis, MD, of the University of Oklahoma Medical Center, Oklahoma City.
“Especially given the rash of legislation across the country aimed at blocking care for transgender youth, it is helpful to show that these treatments really do decrease patients’ anxiety and depressive symptoms,” she said in an interview. “In addition, previous research has been focused on those who have undergone puberty suppression followed by gender-affirming hormone therapy, but many patients are too far along in puberty for puberty suppression to be effective and providers often go straight to gender-affirming hormones in those cases.”
Dr. Lawlis said she was not at all surprised by the study findings. “In my own practice, I have seen patients improve greatly on gender-affirming hormones with overall improvement in anxiety and depression. As a patient’s outward appearance more closely matches their gender identity, they feel more comfortable in their own bodies and their interactions with the world around them, thus improving these symptoms.”
Dr. Lawlis added that the message for pediatricians who treat transgender youth is simple: Gender-affirming hormones improve patient outcomes. “They are essential for the mental health of this vulnerable population.”
She noted that long-term follow-up studies would be useful. “There is still a lot of concern about regret and detransitioning among health care providers and the general population – showing that patients maintain satisfaction in the long-term would be helpful.
“In addition, long-term studies about other health outcomes (cardiovascular disease, cancer risk, etc.) would also be helpful,” said Dr. Lawlis, who was asked to comment on this study, with which she had no involvement.
The study was supported in part by Children’s Health. The researchers had no financial conflicts to disclose. Dr. Lawlis had no relevant financial disclosures.
SOURCE: Kuper LE et al. Pediatrics. 2020 Mar 27. doi: 10.1542/peds.2019-3006.
based on data from 148 individuals.
“Understanding the impact of gender-affirming hormone therapy on the mental health of transgender youth is critical given the health disparities documented in this population,” wrote Laura E. Kuper, PhD, of Children’s Health Systems of Texas, Dallas, and colleagues.
In a study published in Pediatrics, the researchers reviewed data from 148 youth aged 9-18 years who underwent gender-affirming hormone therapy in a multidisciplinary program. The average age of the patients was 15 years; 25 were receiving puberty suppression hormones only, 93 were receiving just feminizing or masculinizing hormones, and 30 were receiving both treatments.
At baseline and at approximately 1 year follow-up, all patients completed the Body Image Scale, Quick Inventory of Depressive Symptoms, and Screen for Child Anxiety Related Emotional Disorders. In addition, clinicians collected information on patients’ suicidal ideation, suicide attempts, and nonsuicidal self-injury.
Overall, the average scores on the Body Image Scale on body dissatisfaction decreased from 70 to 52, and average scores on the Quick Inventory of Depressive Symptoms decreased from 9 to 7; both were statistically significant (P less than .001), as were changes from baseline on the anxiety subscale of the Screen for Child Anxiety Related Emotional Disorders, which decreased from 32 to 29 (P less than .01). No change occurred in the average overall clinician-reported depressive symptoms.
During the follow-up period, the rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury were 38%, 5%, and 17%, respectively. Of patients who reported these experiences, the lifetime histories of suicidal ideation, suicide attempts, and nonsuicidal self-injury were 81%, 15%, and 52%, respectively.
The findings were limited by several factors including some missing data and the relatively small sample size, the researchers noted.
Nonetheless, the results suggest “that youth receiving gender-affirming hormone therapy experience meaningful short-term improvements in body dissatisfaction, and no participants discontinued feminizing or masculinizing hormone therapy.” These results support the use of such therapy, Dr. Kuper and associates wrote.
The study is important because of the need for evidence that hormones actually improve patient outcomes, said Shauna M. Lawlis, MD, of the University of Oklahoma Medical Center, Oklahoma City.
“Especially given the rash of legislation across the country aimed at blocking care for transgender youth, it is helpful to show that these treatments really do decrease patients’ anxiety and depressive symptoms,” she said in an interview. “In addition, previous research has been focused on those who have undergone puberty suppression followed by gender-affirming hormone therapy, but many patients are too far along in puberty for puberty suppression to be effective and providers often go straight to gender-affirming hormones in those cases.”
Dr. Lawlis said she was not at all surprised by the study findings. “In my own practice, I have seen patients improve greatly on gender-affirming hormones with overall improvement in anxiety and depression. As a patient’s outward appearance more closely matches their gender identity, they feel more comfortable in their own bodies and their interactions with the world around them, thus improving these symptoms.”
Dr. Lawlis added that the message for pediatricians who treat transgender youth is simple: Gender-affirming hormones improve patient outcomes. “They are essential for the mental health of this vulnerable population.”
She noted that long-term follow-up studies would be useful. “There is still a lot of concern about regret and detransitioning among health care providers and the general population – showing that patients maintain satisfaction in the long-term would be helpful.
“In addition, long-term studies about other health outcomes (cardiovascular disease, cancer risk, etc.) would also be helpful,” said Dr. Lawlis, who was asked to comment on this study, with which she had no involvement.
The study was supported in part by Children’s Health. The researchers had no financial conflicts to disclose. Dr. Lawlis had no relevant financial disclosures.
SOURCE: Kuper LE et al. Pediatrics. 2020 Mar 27. doi: 10.1542/peds.2019-3006.
based on data from 148 individuals.
“Understanding the impact of gender-affirming hormone therapy on the mental health of transgender youth is critical given the health disparities documented in this population,” wrote Laura E. Kuper, PhD, of Children’s Health Systems of Texas, Dallas, and colleagues.
In a study published in Pediatrics, the researchers reviewed data from 148 youth aged 9-18 years who underwent gender-affirming hormone therapy in a multidisciplinary program. The average age of the patients was 15 years; 25 were receiving puberty suppression hormones only, 93 were receiving just feminizing or masculinizing hormones, and 30 were receiving both treatments.
At baseline and at approximately 1 year follow-up, all patients completed the Body Image Scale, Quick Inventory of Depressive Symptoms, and Screen for Child Anxiety Related Emotional Disorders. In addition, clinicians collected information on patients’ suicidal ideation, suicide attempts, and nonsuicidal self-injury.
Overall, the average scores on the Body Image Scale on body dissatisfaction decreased from 70 to 52, and average scores on the Quick Inventory of Depressive Symptoms decreased from 9 to 7; both were statistically significant (P less than .001), as were changes from baseline on the anxiety subscale of the Screen for Child Anxiety Related Emotional Disorders, which decreased from 32 to 29 (P less than .01). No change occurred in the average overall clinician-reported depressive symptoms.
During the follow-up period, the rates of suicidal ideation, suicide attempts, and nonsuicidal self-injury were 38%, 5%, and 17%, respectively. Of patients who reported these experiences, the lifetime histories of suicidal ideation, suicide attempts, and nonsuicidal self-injury were 81%, 15%, and 52%, respectively.
The findings were limited by several factors including some missing data and the relatively small sample size, the researchers noted.
Nonetheless, the results suggest “that youth receiving gender-affirming hormone therapy experience meaningful short-term improvements in body dissatisfaction, and no participants discontinued feminizing or masculinizing hormone therapy.” These results support the use of such therapy, Dr. Kuper and associates wrote.
The study is important because of the need for evidence that hormones actually improve patient outcomes, said Shauna M. Lawlis, MD, of the University of Oklahoma Medical Center, Oklahoma City.
“Especially given the rash of legislation across the country aimed at blocking care for transgender youth, it is helpful to show that these treatments really do decrease patients’ anxiety and depressive symptoms,” she said in an interview. “In addition, previous research has been focused on those who have undergone puberty suppression followed by gender-affirming hormone therapy, but many patients are too far along in puberty for puberty suppression to be effective and providers often go straight to gender-affirming hormones in those cases.”
Dr. Lawlis said she was not at all surprised by the study findings. “In my own practice, I have seen patients improve greatly on gender-affirming hormones with overall improvement in anxiety and depression. As a patient’s outward appearance more closely matches their gender identity, they feel more comfortable in their own bodies and their interactions with the world around them, thus improving these symptoms.”
Dr. Lawlis added that the message for pediatricians who treat transgender youth is simple: Gender-affirming hormones improve patient outcomes. “They are essential for the mental health of this vulnerable population.”
She noted that long-term follow-up studies would be useful. “There is still a lot of concern about regret and detransitioning among health care providers and the general population – showing that patients maintain satisfaction in the long-term would be helpful.
“In addition, long-term studies about other health outcomes (cardiovascular disease, cancer risk, etc.) would also be helpful,” said Dr. Lawlis, who was asked to comment on this study, with which she had no involvement.
The study was supported in part by Children’s Health. The researchers had no financial conflicts to disclose. Dr. Lawlis had no relevant financial disclosures.
SOURCE: Kuper LE et al. Pediatrics. 2020 Mar 27. doi: 10.1542/peds.2019-3006.
FROM PEDIATRICS
Study challenges role of birth canal exposure in newborn microbiome establishment
During parturient transmission of gut bacteria from mothers to infants, the dominant maternal source of bacteria is rectal, according to investigators.
This challenges the hypothesis that exposure to the birth canal explains major differences in gut bacteria between infants born vaginally and those born via C-section, reported Moran Yassour, PhD, of Hebrew University in Jerusalem.
“It’s not how and if you entered the birth canal, but rather how you exited it,” Dr. Yassour said during a presentation at the annual Gut Microbiota for Health World Summit.
According to Dr. Yassour, a number of investigators have evaluated vertical transmission of gut bacteria from mothers to newborns, but most began collecting data a week or more after birth, potentially missing critical information.
“We wanted to generate large-scale, paired, longitudinal data, which means that we had [samples from] both mothers and children, and we wanted to start at birth,” Dr. Yassour said at the meeting, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.
Dr. Yassour explained that newborns delivered vaginally often exhibit Bacteroides in their gut, whereas babies born via C-section do not exhibit these bacteria until 6-18 months of age; however, the vaginal microbiome typically lacks Bacteroides, making the birth canal an unlikely source. This disconnect served as the impetus for the present investigation, Dr. Yassour said.
The study, which is available as a preprint, involved 73 mothers and their infants. To determine the impact of birth canal exposure, the investigators compared gut bacteria of infants born vaginally with those born via pre-labor C-section (no exposure to the birth canal), and those born via post-labor C-section (exposure to the birth canal).
Initial results were surprising, Dr. Yassour said, as 54% of babies delivered via C-section had Bacteroides in their stool during the first week. But in the second week, 94% of the C-section group lacked Bacteroides, which aligns with characteristic findings and suggests failure of colonization, rather than complete lack of exposure.
Out of the 24 infants with persistent Bacteroides colonization, 22 (92%) were born vaginally, compared with 2 (8%) born via pre-labor C-section, and none born via post-labor C-section. This pattern was maintained in a multivariate analysis that accounted for antibiotic use and exposure to formula, both of which are more common among mothers that give birth via C-section.
The investigators also conducted a strain-level analysis of mothers and infants using metagenomic sequencing. Across all time points, 90% of matched maternal-infant strains were detected in babies delivered vaginally.
“[W]e found evidence for mother-to-child transmission of rectal rather than vaginal strains,” the investigators wrote. “These results challenge birth canal exposure as the dominant factor in infant gut microbiome establishment and implicate colonization efficiency rather than exposure as a dictating factor of the newborn gut microbiome composition.”
Dr. Yassour said that these findings may have an immediate effect on clinical practice.
“People have reported the practice of smearing babies that were born by C-section with vaginal fluids in the sense of trying to recapitulate the microbial signature that we find in kids born vaginally,” Dr. Yassour said. “But it’s probably not the vaginal fluid that we need to smear; it’s probably the proximity to the rectum and the bowel movements that happen during delivery ... and that is what’s causing this initial seeding from mother to child.”
Dr. Yassour disclosed no conflicts of interest.
SOURCE: Yassour M et al. GMFH 2020.
During parturient transmission of gut bacteria from mothers to infants, the dominant maternal source of bacteria is rectal, according to investigators.
This challenges the hypothesis that exposure to the birth canal explains major differences in gut bacteria between infants born vaginally and those born via C-section, reported Moran Yassour, PhD, of Hebrew University in Jerusalem.
“It’s not how and if you entered the birth canal, but rather how you exited it,” Dr. Yassour said during a presentation at the annual Gut Microbiota for Health World Summit.
According to Dr. Yassour, a number of investigators have evaluated vertical transmission of gut bacteria from mothers to newborns, but most began collecting data a week or more after birth, potentially missing critical information.
“We wanted to generate large-scale, paired, longitudinal data, which means that we had [samples from] both mothers and children, and we wanted to start at birth,” Dr. Yassour said at the meeting, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.
Dr. Yassour explained that newborns delivered vaginally often exhibit Bacteroides in their gut, whereas babies born via C-section do not exhibit these bacteria until 6-18 months of age; however, the vaginal microbiome typically lacks Bacteroides, making the birth canal an unlikely source. This disconnect served as the impetus for the present investigation, Dr. Yassour said.
The study, which is available as a preprint, involved 73 mothers and their infants. To determine the impact of birth canal exposure, the investigators compared gut bacteria of infants born vaginally with those born via pre-labor C-section (no exposure to the birth canal), and those born via post-labor C-section (exposure to the birth canal).
Initial results were surprising, Dr. Yassour said, as 54% of babies delivered via C-section had Bacteroides in their stool during the first week. But in the second week, 94% of the C-section group lacked Bacteroides, which aligns with characteristic findings and suggests failure of colonization, rather than complete lack of exposure.
Out of the 24 infants with persistent Bacteroides colonization, 22 (92%) were born vaginally, compared with 2 (8%) born via pre-labor C-section, and none born via post-labor C-section. This pattern was maintained in a multivariate analysis that accounted for antibiotic use and exposure to formula, both of which are more common among mothers that give birth via C-section.
The investigators also conducted a strain-level analysis of mothers and infants using metagenomic sequencing. Across all time points, 90% of matched maternal-infant strains were detected in babies delivered vaginally.
“[W]e found evidence for mother-to-child transmission of rectal rather than vaginal strains,” the investigators wrote. “These results challenge birth canal exposure as the dominant factor in infant gut microbiome establishment and implicate colonization efficiency rather than exposure as a dictating factor of the newborn gut microbiome composition.”
Dr. Yassour said that these findings may have an immediate effect on clinical practice.
“People have reported the practice of smearing babies that were born by C-section with vaginal fluids in the sense of trying to recapitulate the microbial signature that we find in kids born vaginally,” Dr. Yassour said. “But it’s probably not the vaginal fluid that we need to smear; it’s probably the proximity to the rectum and the bowel movements that happen during delivery ... and that is what’s causing this initial seeding from mother to child.”
Dr. Yassour disclosed no conflicts of interest.
SOURCE: Yassour M et al. GMFH 2020.
During parturient transmission of gut bacteria from mothers to infants, the dominant maternal source of bacteria is rectal, according to investigators.
This challenges the hypothesis that exposure to the birth canal explains major differences in gut bacteria between infants born vaginally and those born via C-section, reported Moran Yassour, PhD, of Hebrew University in Jerusalem.
“It’s not how and if you entered the birth canal, but rather how you exited it,” Dr. Yassour said during a presentation at the annual Gut Microbiota for Health World Summit.
According to Dr. Yassour, a number of investigators have evaluated vertical transmission of gut bacteria from mothers to newborns, but most began collecting data a week or more after birth, potentially missing critical information.
“We wanted to generate large-scale, paired, longitudinal data, which means that we had [samples from] both mothers and children, and we wanted to start at birth,” Dr. Yassour said at the meeting, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.
Dr. Yassour explained that newborns delivered vaginally often exhibit Bacteroides in their gut, whereas babies born via C-section do not exhibit these bacteria until 6-18 months of age; however, the vaginal microbiome typically lacks Bacteroides, making the birth canal an unlikely source. This disconnect served as the impetus for the present investigation, Dr. Yassour said.
The study, which is available as a preprint, involved 73 mothers and their infants. To determine the impact of birth canal exposure, the investigators compared gut bacteria of infants born vaginally with those born via pre-labor C-section (no exposure to the birth canal), and those born via post-labor C-section (exposure to the birth canal).
Initial results were surprising, Dr. Yassour said, as 54% of babies delivered via C-section had Bacteroides in their stool during the first week. But in the second week, 94% of the C-section group lacked Bacteroides, which aligns with characteristic findings and suggests failure of colonization, rather than complete lack of exposure.
Out of the 24 infants with persistent Bacteroides colonization, 22 (92%) were born vaginally, compared with 2 (8%) born via pre-labor C-section, and none born via post-labor C-section. This pattern was maintained in a multivariate analysis that accounted for antibiotic use and exposure to formula, both of which are more common among mothers that give birth via C-section.
The investigators also conducted a strain-level analysis of mothers and infants using metagenomic sequencing. Across all time points, 90% of matched maternal-infant strains were detected in babies delivered vaginally.
“[W]e found evidence for mother-to-child transmission of rectal rather than vaginal strains,” the investigators wrote. “These results challenge birth canal exposure as the dominant factor in infant gut microbiome establishment and implicate colonization efficiency rather than exposure as a dictating factor of the newborn gut microbiome composition.”
Dr. Yassour said that these findings may have an immediate effect on clinical practice.
“People have reported the practice of smearing babies that were born by C-section with vaginal fluids in the sense of trying to recapitulate the microbial signature that we find in kids born vaginally,” Dr. Yassour said. “But it’s probably not the vaginal fluid that we need to smear; it’s probably the proximity to the rectum and the bowel movements that happen during delivery ... and that is what’s causing this initial seeding from mother to child.”
Dr. Yassour disclosed no conflicts of interest.
SOURCE: Yassour M et al. GMFH 2020.
FROM GMFH 2020
Two decades of leadership
In recognition of Dr. Larry Wellikson’s contributions to SHM
It’s already been a few years since I exited the Society of Hospital Medicine’s Board of Directors (2 years, or maybe 3 – I’ve already lost count), and sitting in my proverbial rocking chair in the Old Hospitalists’ Home, I heard, as many of you did, that Larry Wellikson, MD, MHM, the first and only CEO in the Society’s history, is stepping down soon.
With all the idle time that I find myself with these days, I have had the opportunity to ruminate on what Larry has brought to SHM in his 2 decades of leadership. And among the many answers, two stand out for me.
The first is Larry’s deep appreciation of the value of relationships that he has developed and nurtured, an attribute which he has imprinted on many of us who have worked with him over the years. Although Larry speaks of the camaraderie of the first years of SHM and the bonds that he, Bob Wachter, Win Whitcomb, and John Nelson established, he also has kept in touch with a vast network of hospitalists over the last 20-plus years.
Go to lunch with Larry, and be amazed at how much he knows about the goings-on of many of our colleagues. The fondness that Larry has for the people in his life is without parallel. These aren’t just professional colleagues who have impacted him in some way – for Larry, every one of these is a true lifetime friendship, and he continues to establish new ones every year. He makes each of his friends feel truly special to him.
The second is the critical value of and need for change and disruption. The specialty of hospital medicine was, from its beginning, disruptive, and from his career as a physician executive, Larry understood and has brought to SHM an understanding of the necessity of disruption to encourage growth and fresh thinking. If one steps back and looks at, for example, the composition of the Board over the years, or the Journal of Hospital Medicine’s editorial staff, or of our committees, one sees a pattern – a commitment to continuously bringing on young leaders who are still on the early and ascending part of their career paths.
Other organizations identify Board candidates at the peak of their careers, but at SHM, many of us were elected when we had just enough experience to contribute but then continued to grow in our careers after finishing our terms. I joined the Board in 2012 (I think) and while I would probably be a more seasoned and stately Board member if I joined at this point in my life, I would also have less new and novel to offer – and therefore be less effective for what the Society needs. While SHM respects its past leaders, it does not revere them. Our past is important, but our present and future are more important. Larry brought that mentality to SHM.
Ironically, the one position within SHM which has not, until this year, been subject to that same kind of transition is the CEO position itself. And this year, that domino will fall as well. While transitions are hard, change is good – and I am confident that our Society’s commitment to seeking out new, talented leaders, and making transitions at all levels – Board, committees, chapters, speakers – with the intent of bringing new perspectives and creativity, is firmly entrenched in our culture. And Larry can join me in the rocking chair as we relive our common SHM experiences together – and create new memories as well.
Congratulations Larry, and thank you.
Dr. Harte is a past president of SHM, and president of Cleveland Clinic Akron (Ohio) General and the Southern Region. He formerly served as president of Cleveland Clinic Hillcrest Hospital and Cleveland Clinic South Pointe Hospital.
In recognition of Dr. Larry Wellikson’s contributions to SHM
In recognition of Dr. Larry Wellikson’s contributions to SHM
It’s already been a few years since I exited the Society of Hospital Medicine’s Board of Directors (2 years, or maybe 3 – I’ve already lost count), and sitting in my proverbial rocking chair in the Old Hospitalists’ Home, I heard, as many of you did, that Larry Wellikson, MD, MHM, the first and only CEO in the Society’s history, is stepping down soon.
With all the idle time that I find myself with these days, I have had the opportunity to ruminate on what Larry has brought to SHM in his 2 decades of leadership. And among the many answers, two stand out for me.
The first is Larry’s deep appreciation of the value of relationships that he has developed and nurtured, an attribute which he has imprinted on many of us who have worked with him over the years. Although Larry speaks of the camaraderie of the first years of SHM and the bonds that he, Bob Wachter, Win Whitcomb, and John Nelson established, he also has kept in touch with a vast network of hospitalists over the last 20-plus years.
Go to lunch with Larry, and be amazed at how much he knows about the goings-on of many of our colleagues. The fondness that Larry has for the people in his life is without parallel. These aren’t just professional colleagues who have impacted him in some way – for Larry, every one of these is a true lifetime friendship, and he continues to establish new ones every year. He makes each of his friends feel truly special to him.
The second is the critical value of and need for change and disruption. The specialty of hospital medicine was, from its beginning, disruptive, and from his career as a physician executive, Larry understood and has brought to SHM an understanding of the necessity of disruption to encourage growth and fresh thinking. If one steps back and looks at, for example, the composition of the Board over the years, or the Journal of Hospital Medicine’s editorial staff, or of our committees, one sees a pattern – a commitment to continuously bringing on young leaders who are still on the early and ascending part of their career paths.
Other organizations identify Board candidates at the peak of their careers, but at SHM, many of us were elected when we had just enough experience to contribute but then continued to grow in our careers after finishing our terms. I joined the Board in 2012 (I think) and while I would probably be a more seasoned and stately Board member if I joined at this point in my life, I would also have less new and novel to offer – and therefore be less effective for what the Society needs. While SHM respects its past leaders, it does not revere them. Our past is important, but our present and future are more important. Larry brought that mentality to SHM.
Ironically, the one position within SHM which has not, until this year, been subject to that same kind of transition is the CEO position itself. And this year, that domino will fall as well. While transitions are hard, change is good – and I am confident that our Society’s commitment to seeking out new, talented leaders, and making transitions at all levels – Board, committees, chapters, speakers – with the intent of bringing new perspectives and creativity, is firmly entrenched in our culture. And Larry can join me in the rocking chair as we relive our common SHM experiences together – and create new memories as well.
Congratulations Larry, and thank you.
Dr. Harte is a past president of SHM, and president of Cleveland Clinic Akron (Ohio) General and the Southern Region. He formerly served as president of Cleveland Clinic Hillcrest Hospital and Cleveland Clinic South Pointe Hospital.
It’s already been a few years since I exited the Society of Hospital Medicine’s Board of Directors (2 years, or maybe 3 – I’ve already lost count), and sitting in my proverbial rocking chair in the Old Hospitalists’ Home, I heard, as many of you did, that Larry Wellikson, MD, MHM, the first and only CEO in the Society’s history, is stepping down soon.
With all the idle time that I find myself with these days, I have had the opportunity to ruminate on what Larry has brought to SHM in his 2 decades of leadership. And among the many answers, two stand out for me.
The first is Larry’s deep appreciation of the value of relationships that he has developed and nurtured, an attribute which he has imprinted on many of us who have worked with him over the years. Although Larry speaks of the camaraderie of the first years of SHM and the bonds that he, Bob Wachter, Win Whitcomb, and John Nelson established, he also has kept in touch with a vast network of hospitalists over the last 20-plus years.
Go to lunch with Larry, and be amazed at how much he knows about the goings-on of many of our colleagues. The fondness that Larry has for the people in his life is without parallel. These aren’t just professional colleagues who have impacted him in some way – for Larry, every one of these is a true lifetime friendship, and he continues to establish new ones every year. He makes each of his friends feel truly special to him.
The second is the critical value of and need for change and disruption. The specialty of hospital medicine was, from its beginning, disruptive, and from his career as a physician executive, Larry understood and has brought to SHM an understanding of the necessity of disruption to encourage growth and fresh thinking. If one steps back and looks at, for example, the composition of the Board over the years, or the Journal of Hospital Medicine’s editorial staff, or of our committees, one sees a pattern – a commitment to continuously bringing on young leaders who are still on the early and ascending part of their career paths.
Other organizations identify Board candidates at the peak of their careers, but at SHM, many of us were elected when we had just enough experience to contribute but then continued to grow in our careers after finishing our terms. I joined the Board in 2012 (I think) and while I would probably be a more seasoned and stately Board member if I joined at this point in my life, I would also have less new and novel to offer – and therefore be less effective for what the Society needs. While SHM respects its past leaders, it does not revere them. Our past is important, but our present and future are more important. Larry brought that mentality to SHM.
Ironically, the one position within SHM which has not, until this year, been subject to that same kind of transition is the CEO position itself. And this year, that domino will fall as well. While transitions are hard, change is good – and I am confident that our Society’s commitment to seeking out new, talented leaders, and making transitions at all levels – Board, committees, chapters, speakers – with the intent of bringing new perspectives and creativity, is firmly entrenched in our culture. And Larry can join me in the rocking chair as we relive our common SHM experiences together – and create new memories as well.
Congratulations Larry, and thank you.
Dr. Harte is a past president of SHM, and president of Cleveland Clinic Akron (Ohio) General and the Southern Region. He formerly served as president of Cleveland Clinic Hillcrest Hospital and Cleveland Clinic South Pointe Hospital.
Targeting gut bacteria may improve levodopa uptake
Differences in metabolism of levodopa between patients with Parkinson’s disease may be caused by variations in gut bacteria, according to investigators.
Specifically, patients with a higher abundance of Enterococcus faecalis may be converting levodopa into dopamine via decarboxylation before it can cross the blood-brain barrier, reported Emily P. Balskus, PhD, of Harvard University in Cambridge, Mass.
Although existing decarboxylase inhibitors, such as carbidopa, can reduce metabolism of levodopa by host enzymes, these drugs are unable to inhibit the enzymatic activity of E. faecalis in the gut, Dr. Balskus said at the annual Gut Microbiota for Health World Summit, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.
“[Carbidopa] is actually completely ineffective at inhibiting decarboxylation in human fecal suspension,” Dr. Balskus said, referring to research led by PhD student Vayu Maini Rekdal. “We think that this could indicate that patients who are taking carbidopa are not inhibiting any bacterial metabolism that they may have.”
While previous research showed that E. faecalis could decarboxylate levodopa, Dr. Balskus and colleagues linked this process with the tyrosine decarboxylase gene (TyrDC), and showed that the of abundance E. faecalis and TyrDC correlate with levodopa metabolism.
Unlike the human enzyme responsible for decarboxylation of levodopa, the E. faecalis enzyme preferentially binds with L-tyrosine. This could explain why existing decarboxylase inhibitors have little impact on decarboxylation in the gut, Dr. Balskus said.
She also noted that this unique characteristic may open doors to new therapeutics. In the lab, Dr. Balskus and colleagues tested a decarboxylase inhibitor that resembled L-tyrosine, (S)-alpha-fluoromethyltyrosine (AFMT). Indeed, AFMT completely inhibited of decarboxylation of levodopa in both E. faecalis cells and complex human microbiome samples.
“We think this is pretty exciting,” Dr. Balskus said.
Early animal studies support this enthusiasm, as germ-free mice colonized with E. faecalis maintain higher serum levels of levodopa with concurrent administration of AFMT.
“We think that this could indicate that a promising way to improve levodopa therapy for Parkinson’s patients would be to develop compounds that inhibit bacterial drug metabolism activity,” Dr. Balskus said.
Concluding her presentation, Dr. Balskus emphasized the importance of a biochemical approach to microbiome research. “Studying enzymes opens up new, exciting opportunities for microbiome manipulation. We can design or develop inhibitors of enzymes, use those inhibitors as tools to study the roles of individual metabolic activities, and potentially use them as therapeutics. We are very excited about the possibility of treating or preventing human disease not just by manipulating processes in our own cells, but by targeting activities in the microbiota.”
Dr. Balskus reported funding from HHMI, the Bill and Melinda Gates Foundation, the David and Lucile Packard Foundation, and Merck.
Differences in metabolism of levodopa between patients with Parkinson’s disease may be caused by variations in gut bacteria, according to investigators.
Specifically, patients with a higher abundance of Enterococcus faecalis may be converting levodopa into dopamine via decarboxylation before it can cross the blood-brain barrier, reported Emily P. Balskus, PhD, of Harvard University in Cambridge, Mass.
Although existing decarboxylase inhibitors, such as carbidopa, can reduce metabolism of levodopa by host enzymes, these drugs are unable to inhibit the enzymatic activity of E. faecalis in the gut, Dr. Balskus said at the annual Gut Microbiota for Health World Summit, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.
“[Carbidopa] is actually completely ineffective at inhibiting decarboxylation in human fecal suspension,” Dr. Balskus said, referring to research led by PhD student Vayu Maini Rekdal. “We think that this could indicate that patients who are taking carbidopa are not inhibiting any bacterial metabolism that they may have.”
While previous research showed that E. faecalis could decarboxylate levodopa, Dr. Balskus and colleagues linked this process with the tyrosine decarboxylase gene (TyrDC), and showed that the of abundance E. faecalis and TyrDC correlate with levodopa metabolism.
Unlike the human enzyme responsible for decarboxylation of levodopa, the E. faecalis enzyme preferentially binds with L-tyrosine. This could explain why existing decarboxylase inhibitors have little impact on decarboxylation in the gut, Dr. Balskus said.
She also noted that this unique characteristic may open doors to new therapeutics. In the lab, Dr. Balskus and colleagues tested a decarboxylase inhibitor that resembled L-tyrosine, (S)-alpha-fluoromethyltyrosine (AFMT). Indeed, AFMT completely inhibited of decarboxylation of levodopa in both E. faecalis cells and complex human microbiome samples.
“We think this is pretty exciting,” Dr. Balskus said.
Early animal studies support this enthusiasm, as germ-free mice colonized with E. faecalis maintain higher serum levels of levodopa with concurrent administration of AFMT.
“We think that this could indicate that a promising way to improve levodopa therapy for Parkinson’s patients would be to develop compounds that inhibit bacterial drug metabolism activity,” Dr. Balskus said.
Concluding her presentation, Dr. Balskus emphasized the importance of a biochemical approach to microbiome research. “Studying enzymes opens up new, exciting opportunities for microbiome manipulation. We can design or develop inhibitors of enzymes, use those inhibitors as tools to study the roles of individual metabolic activities, and potentially use them as therapeutics. We are very excited about the possibility of treating or preventing human disease not just by manipulating processes in our own cells, but by targeting activities in the microbiota.”
Dr. Balskus reported funding from HHMI, the Bill and Melinda Gates Foundation, the David and Lucile Packard Foundation, and Merck.
Differences in metabolism of levodopa between patients with Parkinson’s disease may be caused by variations in gut bacteria, according to investigators.
Specifically, patients with a higher abundance of Enterococcus faecalis may be converting levodopa into dopamine via decarboxylation before it can cross the blood-brain barrier, reported Emily P. Balskus, PhD, of Harvard University in Cambridge, Mass.
Although existing decarboxylase inhibitors, such as carbidopa, can reduce metabolism of levodopa by host enzymes, these drugs are unable to inhibit the enzymatic activity of E. faecalis in the gut, Dr. Balskus said at the annual Gut Microbiota for Health World Summit, sponsored by the American Gastroenterological Association and the European Society for Neurogastroenterology and Motility.
“[Carbidopa] is actually completely ineffective at inhibiting decarboxylation in human fecal suspension,” Dr. Balskus said, referring to research led by PhD student Vayu Maini Rekdal. “We think that this could indicate that patients who are taking carbidopa are not inhibiting any bacterial metabolism that they may have.”
While previous research showed that E. faecalis could decarboxylate levodopa, Dr. Balskus and colleagues linked this process with the tyrosine decarboxylase gene (TyrDC), and showed that the of abundance E. faecalis and TyrDC correlate with levodopa metabolism.
Unlike the human enzyme responsible for decarboxylation of levodopa, the E. faecalis enzyme preferentially binds with L-tyrosine. This could explain why existing decarboxylase inhibitors have little impact on decarboxylation in the gut, Dr. Balskus said.
She also noted that this unique characteristic may open doors to new therapeutics. In the lab, Dr. Balskus and colleagues tested a decarboxylase inhibitor that resembled L-tyrosine, (S)-alpha-fluoromethyltyrosine (AFMT). Indeed, AFMT completely inhibited of decarboxylation of levodopa in both E. faecalis cells and complex human microbiome samples.
“We think this is pretty exciting,” Dr. Balskus said.
Early animal studies support this enthusiasm, as germ-free mice colonized with E. faecalis maintain higher serum levels of levodopa with concurrent administration of AFMT.
“We think that this could indicate that a promising way to improve levodopa therapy for Parkinson’s patients would be to develop compounds that inhibit bacterial drug metabolism activity,” Dr. Balskus said.
Concluding her presentation, Dr. Balskus emphasized the importance of a biochemical approach to microbiome research. “Studying enzymes opens up new, exciting opportunities for microbiome manipulation. We can design or develop inhibitors of enzymes, use those inhibitors as tools to study the roles of individual metabolic activities, and potentially use them as therapeutics. We are very excited about the possibility of treating or preventing human disease not just by manipulating processes in our own cells, but by targeting activities in the microbiota.”
Dr. Balskus reported funding from HHMI, the Bill and Melinda Gates Foundation, the David and Lucile Packard Foundation, and Merck.
FROM GMFH 2020
Despite strict controls, some infants born to mothers with COVID-19 appear infected
Despite implementation of strict infection control and prevention procedures in a hospital in Wuhan, China, according to Lingkong Zeng, MD, of the department of neonatology at Wuhan Children’s Hospital, and associates.
Thirty-three neonates born to mothers with COVID-19 were included in the study, published as a research letter in JAMA Pediatrics. Of this group, three neonates (9%) were confirmed to be infected with the novel coronavirus 2019 at 2 and 4 days of life through nasopharyngeal and anal swabs.
Of the three infected neonates, two were born at 40 weeks’ gestation and the third was born at 31 weeks. The two full-term infants had mild symptoms such as lethargy and fever and were negative for the virus at 6 days of life. The preterm infant had somewhat worse symptoms, but the investigators acknowledged that “the most seriously ill neonate may have been symptomatic from prematurity, asphyxia, and sepsis, rather than [the novel coronavirus 2019] infection.” They added that outcomes for all three neonates were favorable, consistent with past research.
“Because strict infection control and prevention procedures were implemented during the delivery, it is likely that the sources of [novel coronavirus 2019] in the neonates’ upper respiratory tracts or anuses were maternal in origin,” Dr. Zeng and associates surmised.
While previous studies have shown no evidence of COVID-19 transmission between mothers and neonates, and all samples, including amniotic fluid, cord blood, and breast milk, were negative for the novel coronavirus 2019, “vertical maternal-fetal transmission cannot be ruled out in the current cohort. Therefore, it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19,” the investigators concluded.
The study authors reported that they had no conflicts of interest.
SOURCE: Zeng L et al. JAMA Pediatrics. 2020 Mar 26. doi: 10.1001/jamapediatrics.2020.0878.
Despite implementation of strict infection control and prevention procedures in a hospital in Wuhan, China, according to Lingkong Zeng, MD, of the department of neonatology at Wuhan Children’s Hospital, and associates.
Thirty-three neonates born to mothers with COVID-19 were included in the study, published as a research letter in JAMA Pediatrics. Of this group, three neonates (9%) were confirmed to be infected with the novel coronavirus 2019 at 2 and 4 days of life through nasopharyngeal and anal swabs.
Of the three infected neonates, two were born at 40 weeks’ gestation and the third was born at 31 weeks. The two full-term infants had mild symptoms such as lethargy and fever and were negative for the virus at 6 days of life. The preterm infant had somewhat worse symptoms, but the investigators acknowledged that “the most seriously ill neonate may have been symptomatic from prematurity, asphyxia, and sepsis, rather than [the novel coronavirus 2019] infection.” They added that outcomes for all three neonates were favorable, consistent with past research.
“Because strict infection control and prevention procedures were implemented during the delivery, it is likely that the sources of [novel coronavirus 2019] in the neonates’ upper respiratory tracts or anuses were maternal in origin,” Dr. Zeng and associates surmised.
While previous studies have shown no evidence of COVID-19 transmission between mothers and neonates, and all samples, including amniotic fluid, cord blood, and breast milk, were negative for the novel coronavirus 2019, “vertical maternal-fetal transmission cannot be ruled out in the current cohort. Therefore, it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19,” the investigators concluded.
The study authors reported that they had no conflicts of interest.
SOURCE: Zeng L et al. JAMA Pediatrics. 2020 Mar 26. doi: 10.1001/jamapediatrics.2020.0878.
Despite implementation of strict infection control and prevention procedures in a hospital in Wuhan, China, according to Lingkong Zeng, MD, of the department of neonatology at Wuhan Children’s Hospital, and associates.
Thirty-three neonates born to mothers with COVID-19 were included in the study, published as a research letter in JAMA Pediatrics. Of this group, three neonates (9%) were confirmed to be infected with the novel coronavirus 2019 at 2 and 4 days of life through nasopharyngeal and anal swabs.
Of the three infected neonates, two were born at 40 weeks’ gestation and the third was born at 31 weeks. The two full-term infants had mild symptoms such as lethargy and fever and were negative for the virus at 6 days of life. The preterm infant had somewhat worse symptoms, but the investigators acknowledged that “the most seriously ill neonate may have been symptomatic from prematurity, asphyxia, and sepsis, rather than [the novel coronavirus 2019] infection.” They added that outcomes for all three neonates were favorable, consistent with past research.
“Because strict infection control and prevention procedures were implemented during the delivery, it is likely that the sources of [novel coronavirus 2019] in the neonates’ upper respiratory tracts or anuses were maternal in origin,” Dr. Zeng and associates surmised.
While previous studies have shown no evidence of COVID-19 transmission between mothers and neonates, and all samples, including amniotic fluid, cord blood, and breast milk, were negative for the novel coronavirus 2019, “vertical maternal-fetal transmission cannot be ruled out in the current cohort. Therefore, it is crucial to screen pregnant women and implement strict infection control measures, quarantine of infected mothers, and close monitoring of neonates at risk of COVID-19,” the investigators concluded.
The study authors reported that they had no conflicts of interest.
SOURCE: Zeng L et al. JAMA Pediatrics. 2020 Mar 26. doi: 10.1001/jamapediatrics.2020.0878.
FROM JAMA PEDIATRICS
