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Near-Death Experiences During CPR: An Impetus for Better Care
If someone has been in cardiac arrest for 10 minutes, the brain is permanently damaged and there’s nothing to do, right?
Not so according to emerging evidence that suggests that the brain shows signs of electrical recovery for as long as an hour into ongoing cardiopulmonary resuscitation (CPR). This time between cardiac arrest and awakening can be a period of vivid experiences for the dying patient before they return to life — a phenomenon known as “recalled death.”
This should be an impetus to increase the use of devices that measure the quality of CPR and to find new treatments to restart the heart or prevent brain injury, experts advised. Cardiologists and critical care clinicians are among those who will need to manage patients in the aftermath.
said Jasmeet Soar, MD, consultant in Anesthetics & Intensive Care Medicine, North Bristol NHS Trust, Bristol, England, and an editor of the journal Resuscitation.
“We know that because if chest compressions are stopped, the person becomes unconscious again,” he said. “This CPR-induced consciousness has become more common when professionals do the CPR because resuscitation guidelines now place a much bigger focus on high-quality CPR — ‘push hard, push fast.’ ”
“People are giving up too soon on trying to revive individuals, and they should be trying more modern strategies, such as extracorporeal membrane oxygenation,” said Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, New York City.
Brain Activity, Heightened Experiences
Two types of brain activity may occur when CPR works. The first, called CPR-induced consciousness, is when an individual recovers consciousness while in cardiac arrest. Signs of consciousness include combativeness, groaning, and eye-opening, Soar explained.
The second type is a perception of lucidity with recall of events, he said. “Patients who experience this may form memories that they can recall. We’re not sure whether that happens during CPR or while the patient is waking up during intensive care, or how the brain creates these memories, or if they’re real memories or coincidental, but it’s clear the brain does form them during the dying and recovery process.”
This latter phenomenon was explored in detail in a recent study led by Dr. Parnia.
In that study of 567 in-hospital patients with cardiac arrest from 25 centers in the United States and United Kingdom, 53 survived, 28 of those survivors were interviewed, and 11 reported memories or perceptions suggestive of consciousness.
Four types of experiences occurred:
- Recalled experiences of death: “I thought I heard my grandma [who had passed] saying ‘you need to go back.’”
- Emergence from coma during CPR/CPR-induced consciousness: “I remember when I came back and they were putting those two electrodes to my chest, and I remember the shock.”
- Emergence from coma in the post-resuscitation period: “I heard my partner saying [patient’s name] and my son saying ‘mom.’”
- Dreams and dream-like experiences: “[I] felt as though someone was holding my hand. It was very black; I couldn’t see anything.”
In a complementary cross-sectional study, 126 community cardiac arrest survivors reported similar experiences plus a fifth type, “delusions,” or “misattribution of medical events,” for example, “I heard my name, over and over again. All around me were things like demons and monsters. It felt like they were trying to tear off my body parts.”
“Many people label recalled experiences of death as ‘near-death’ experiences, but they’re not,” Dr. Parnia said. “Medically speaking, being near to death means your heart is about to stop. But the whole point is that these people are not near death. They actually died and came back from it.”
One of the big implications of the study, he said, is that “a lot of physicians are taught that somehow after, say, 3-5 minutes of oxygen deprivation, the brain dies. Our study showed this is not true. It showed that the brain may not be functioning, which is why they flatline. But if you’re able to resuscitate them appropriately, you can restore activity up to an hour later.”
Because some clinicians questioned or dismissed previous work in this area by Dr. Parnia and others, the latest study used EEG monitoring in a subset of 53 patients. Among those with evaluable EEG data, brain activity returned to normal or near-normal after flatlining in about 40% of images; spikes were seen in the delta (22%), theta (12%), alpha (6%), and beta (1%) waves associated with higher mental function.
“The team recorded what was happening in the brain during real-time CPR using various tests of consciousness, including EEG measurements and tests of visual and auditory awareness using a tablet with a special app and a Bluetooth headphone.”
“Incredibly, we found that even though the brain flatlines, which is what we expect when the heart stops, with professionally given CPR even up to about an hour after this, the brainwaves changed into normal to near-normal patterns,” Dr. Parnia said. “We were able to identify these brain waves in patients while they were being resuscitated, which confirms the fact that people can have lucid consciousness even though they appear to be unconscious.”
Asked what implications, if any, his work has for current definitions of brain death and cardiac death, Dr. Parnia said that the problem is that these are based on the concept of “a permanent irreversible loss of function,” but “that’s only relative to what medical treatments are developed at a given time.”
Potential Mechanism
Dr. Parnia and his team proposed a potential mechanism for recalled experiences of death. Essentially, when the brain flatlines, the dying brain removes natural inhibitory (braking) systems that are needed to support daily functioning. This disinhibition may open access to “new dimensions of reality, including lucid recall of stored memories from early childhood to death,” he said.
From a clinical perspective, he noted, “although the brain stops working when it flatlines, it does not die within 5 or 10 minutes of oxygen deprivation.”
This is contrary to what many doctors believe, and because of that, he said, “nobody has tried to find treatments or new ways to restart the heart or prevent brain injury. They think it’s futile. So, with this work, we’ve opened up the window to developing cocktails of drugs that could be given to patients who have technically gone through death to bring them back to life again.”
Probe Patients or Leave Well Enough Alone?
The findings have ramifications for clinicians who may be caring for patients who survive cardiac arrest, said Lance B. Becker, MD, professor and chair, Department of Emergency Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, and chair, Department of Emergency Medicine at North Shore University Hospital, Manhasset, and Long Island Jewish Medical Center, Queens, New York.
“I’ve talked with a lot of patients who have had some kind of recalled experience around cardiac arrest and some who have had zero recall, as well, like in the paper,” he told this news organization. “The ones who do have an experience are sometimes mystified by it and have questions. And very often, clinicians don’t want to listen, don’t think it’s important, and downplay it.”
“I think it is important, and when people have important things happen to them, it’s really imperative that doctors listen, learn, and respond,” he said. “When I started in this field a long time ago, there were so few survivors that there wasn’t even a concept of survivorship,” he said.
Dr. Becker noted that it’s not uncommon for cardiac arrest survivors to have depression, problems with executive function, or a small brain injury they need to recover from. “Now survivorship organizations are springing up that these people can turn to, but clinicians still need to become more aware and sensitive to this.”
Not all are. “I had a number of patients who said I was the only doctor who ever asked them about what they experienced,” he recalled. “I was a young doctor at the time and didn’t exactly know what to say to them, but they were just happy to have a doctor who would listen to them and not be afraid to hear what they had to say.”
Recognizing that support is an issue, the American Heart Association released a scientific statement in 2020 on sudden cardiac arrest survivorship, which “expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac survivorship.”
Soar has a more nuanced view of survivorship support, however. “I suspect some people are very glad to be alive, and that trying to dig deep and bring things out may actually be harmful,” he said. “It’s not as clear cut as everybody thinks.”
He noted that follow-up and rehabilitation should be an option for people who specifically need it who would need to be identified. “But human beings are resilient, and while some people will require help, not everybody will,” he said.
Better CPR, New Treatments
Experts in emergency and intensive care medicine studying survival after cardiac arrest hope to find ways to save patients before too much damage is done to the brain and other organs from loss of oxygen, Dr. Parnia said. He is the lead author in a recent multidisciplinary consensus statement on guidelines and standards for the study of death and recalled experiences of death.
“One of my bugbears is that our survival outcomes from cardiac arrest resuscitation have not changed very much for 60 years because we haven’t developed new treatments and innovative methods,” he said. “Unlike the rest of medicine, we’re living in the past.”
Currently, his team is developing cocktails of treatments. These include hypothermic circulatory arrest — cooling the body to stop blood circulation and brain function for up to 40 minutes — and giving magnesium, a brain-protective treatment, to people whose hearts stop.
Dr. Becker would like to see optimal care of patients with cardiac arrest. “The first step is to increase blood flow with good CPR and then measure whether CPR is working,” he said. Adding that despite the availability of devices that provide feedback on the quality of CPR, they’re rarely used. He cited ultrasound devices that measure the blood flow generated during CPR, compression meter devices that go between the patient’s chest and the rescuer’s hands that gauge the rate and depth of compression, and invasive devices that measure blood pressure during CPR.
His group is trying to design even better devices, he said. “An example would be a little probe that you could pop on the neck that would study blood flow to the brain with ultrasound, so that while you were pumping on the person, you could see if you’re making them better or not.”
“We also have some preliminary data showing that the American Heart Association recommended position on the chest for doing CPR is not the perfect place for everybody,” he said. The 2020 AHA guidelines recommended the center of the lower half of the sternum. At the 2023 American College of Emergency Physicians meeting, Dr. Becker›s team at Hofstra/Northwell presented data on 175 video-recorded adult cardiac arrests in their emergency department over more than 2 years, 22 of which involved at least one change of compression location (for a total of 29 location changes). They found that 41% of compression location changes were associated with return of spontaneous circulation.
For about a third of people, the hands need to be repositioned slightly. “This is not anything that is taught to the public because you can only figure it out if you have some kind of sensor that will let you know how you’re doing. That’s very achievable. We could have that in the future on every ambulance and even in people’s homes.”
When the person arrives at the hospital, he said, “we can make it easier and more likely that they can be put on extracorporeal membrane oxygenation (ECMO). We do that on selected patients in our hospital, even though it’s very difficult to do, because we know that when it’s done properly, it can change survival rates dramatically, from maybe 10%-50%.”
Dr. Dr. Becker, like Dr. Parnia, also favors the development of drug cocktails, and his team has been experimenting with various combinations in animal models. “We think those two things together — ECMO and a drug cocktail — would be a very powerful one to two knock out for cardiac arrest,” he said. “We have a long way to go — 10 or 20 years. But most people around the world working in this area believe that will be the future.”
Dr. Parnia’s study on recalled death was supported by The John Templeton Foundation, Resuscitation Council (UK), and New York University Grossman School of Medicine, with research support staff provided by the UK’s National Institutes for Health Research. Soar is the editor of the journal Resuscitation and receives payment from the publisher Elsevier. Dr. Becker’s institute has received grants from Philips Medical Systems, NIH, Zoll Medical Corp, Nihon Kohden, PCORI, BrainCool, and United Therapeutics. He has received advisory/consultancy honoraria from NIH, Nihon Kohden, HP, and Philips, and he holds several patents in hypothermia induction and reperfusion therapies and several pending patents involving the use of medical slurries as human coolant devices to create reperfusion cocktails and measurement of respiratory quotient.
A version of this article appeared on Medscape.com.
If someone has been in cardiac arrest for 10 minutes, the brain is permanently damaged and there’s nothing to do, right?
Not so according to emerging evidence that suggests that the brain shows signs of electrical recovery for as long as an hour into ongoing cardiopulmonary resuscitation (CPR). This time between cardiac arrest and awakening can be a period of vivid experiences for the dying patient before they return to life — a phenomenon known as “recalled death.”
This should be an impetus to increase the use of devices that measure the quality of CPR and to find new treatments to restart the heart or prevent brain injury, experts advised. Cardiologists and critical care clinicians are among those who will need to manage patients in the aftermath.
said Jasmeet Soar, MD, consultant in Anesthetics & Intensive Care Medicine, North Bristol NHS Trust, Bristol, England, and an editor of the journal Resuscitation.
“We know that because if chest compressions are stopped, the person becomes unconscious again,” he said. “This CPR-induced consciousness has become more common when professionals do the CPR because resuscitation guidelines now place a much bigger focus on high-quality CPR — ‘push hard, push fast.’ ”
“People are giving up too soon on trying to revive individuals, and they should be trying more modern strategies, such as extracorporeal membrane oxygenation,” said Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, New York City.
Brain Activity, Heightened Experiences
Two types of brain activity may occur when CPR works. The first, called CPR-induced consciousness, is when an individual recovers consciousness while in cardiac arrest. Signs of consciousness include combativeness, groaning, and eye-opening, Soar explained.
The second type is a perception of lucidity with recall of events, he said. “Patients who experience this may form memories that they can recall. We’re not sure whether that happens during CPR or while the patient is waking up during intensive care, or how the brain creates these memories, or if they’re real memories or coincidental, but it’s clear the brain does form them during the dying and recovery process.”
This latter phenomenon was explored in detail in a recent study led by Dr. Parnia.
In that study of 567 in-hospital patients with cardiac arrest from 25 centers in the United States and United Kingdom, 53 survived, 28 of those survivors were interviewed, and 11 reported memories or perceptions suggestive of consciousness.
Four types of experiences occurred:
- Recalled experiences of death: “I thought I heard my grandma [who had passed] saying ‘you need to go back.’”
- Emergence from coma during CPR/CPR-induced consciousness: “I remember when I came back and they were putting those two electrodes to my chest, and I remember the shock.”
- Emergence from coma in the post-resuscitation period: “I heard my partner saying [patient’s name] and my son saying ‘mom.’”
- Dreams and dream-like experiences: “[I] felt as though someone was holding my hand. It was very black; I couldn’t see anything.”
In a complementary cross-sectional study, 126 community cardiac arrest survivors reported similar experiences plus a fifth type, “delusions,” or “misattribution of medical events,” for example, “I heard my name, over and over again. All around me were things like demons and monsters. It felt like they were trying to tear off my body parts.”
“Many people label recalled experiences of death as ‘near-death’ experiences, but they’re not,” Dr. Parnia said. “Medically speaking, being near to death means your heart is about to stop. But the whole point is that these people are not near death. They actually died and came back from it.”
One of the big implications of the study, he said, is that “a lot of physicians are taught that somehow after, say, 3-5 minutes of oxygen deprivation, the brain dies. Our study showed this is not true. It showed that the brain may not be functioning, which is why they flatline. But if you’re able to resuscitate them appropriately, you can restore activity up to an hour later.”
Because some clinicians questioned or dismissed previous work in this area by Dr. Parnia and others, the latest study used EEG monitoring in a subset of 53 patients. Among those with evaluable EEG data, brain activity returned to normal or near-normal after flatlining in about 40% of images; spikes were seen in the delta (22%), theta (12%), alpha (6%), and beta (1%) waves associated with higher mental function.
“The team recorded what was happening in the brain during real-time CPR using various tests of consciousness, including EEG measurements and tests of visual and auditory awareness using a tablet with a special app and a Bluetooth headphone.”
“Incredibly, we found that even though the brain flatlines, which is what we expect when the heart stops, with professionally given CPR even up to about an hour after this, the brainwaves changed into normal to near-normal patterns,” Dr. Parnia said. “We were able to identify these brain waves in patients while they were being resuscitated, which confirms the fact that people can have lucid consciousness even though they appear to be unconscious.”
Asked what implications, if any, his work has for current definitions of brain death and cardiac death, Dr. Parnia said that the problem is that these are based on the concept of “a permanent irreversible loss of function,” but “that’s only relative to what medical treatments are developed at a given time.”
Potential Mechanism
Dr. Parnia and his team proposed a potential mechanism for recalled experiences of death. Essentially, when the brain flatlines, the dying brain removes natural inhibitory (braking) systems that are needed to support daily functioning. This disinhibition may open access to “new dimensions of reality, including lucid recall of stored memories from early childhood to death,” he said.
From a clinical perspective, he noted, “although the brain stops working when it flatlines, it does not die within 5 or 10 minutes of oxygen deprivation.”
This is contrary to what many doctors believe, and because of that, he said, “nobody has tried to find treatments or new ways to restart the heart or prevent brain injury. They think it’s futile. So, with this work, we’ve opened up the window to developing cocktails of drugs that could be given to patients who have technically gone through death to bring them back to life again.”
Probe Patients or Leave Well Enough Alone?
The findings have ramifications for clinicians who may be caring for patients who survive cardiac arrest, said Lance B. Becker, MD, professor and chair, Department of Emergency Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, and chair, Department of Emergency Medicine at North Shore University Hospital, Manhasset, and Long Island Jewish Medical Center, Queens, New York.
“I’ve talked with a lot of patients who have had some kind of recalled experience around cardiac arrest and some who have had zero recall, as well, like in the paper,” he told this news organization. “The ones who do have an experience are sometimes mystified by it and have questions. And very often, clinicians don’t want to listen, don’t think it’s important, and downplay it.”
“I think it is important, and when people have important things happen to them, it’s really imperative that doctors listen, learn, and respond,” he said. “When I started in this field a long time ago, there were so few survivors that there wasn’t even a concept of survivorship,” he said.
Dr. Becker noted that it’s not uncommon for cardiac arrest survivors to have depression, problems with executive function, or a small brain injury they need to recover from. “Now survivorship organizations are springing up that these people can turn to, but clinicians still need to become more aware and sensitive to this.”
Not all are. “I had a number of patients who said I was the only doctor who ever asked them about what they experienced,” he recalled. “I was a young doctor at the time and didn’t exactly know what to say to them, but they were just happy to have a doctor who would listen to them and not be afraid to hear what they had to say.”
Recognizing that support is an issue, the American Heart Association released a scientific statement in 2020 on sudden cardiac arrest survivorship, which “expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac survivorship.”
Soar has a more nuanced view of survivorship support, however. “I suspect some people are very glad to be alive, and that trying to dig deep and bring things out may actually be harmful,” he said. “It’s not as clear cut as everybody thinks.”
He noted that follow-up and rehabilitation should be an option for people who specifically need it who would need to be identified. “But human beings are resilient, and while some people will require help, not everybody will,” he said.
Better CPR, New Treatments
Experts in emergency and intensive care medicine studying survival after cardiac arrest hope to find ways to save patients before too much damage is done to the brain and other organs from loss of oxygen, Dr. Parnia said. He is the lead author in a recent multidisciplinary consensus statement on guidelines and standards for the study of death and recalled experiences of death.
“One of my bugbears is that our survival outcomes from cardiac arrest resuscitation have not changed very much for 60 years because we haven’t developed new treatments and innovative methods,” he said. “Unlike the rest of medicine, we’re living in the past.”
Currently, his team is developing cocktails of treatments. These include hypothermic circulatory arrest — cooling the body to stop blood circulation and brain function for up to 40 minutes — and giving magnesium, a brain-protective treatment, to people whose hearts stop.
Dr. Becker would like to see optimal care of patients with cardiac arrest. “The first step is to increase blood flow with good CPR and then measure whether CPR is working,” he said. Adding that despite the availability of devices that provide feedback on the quality of CPR, they’re rarely used. He cited ultrasound devices that measure the blood flow generated during CPR, compression meter devices that go between the patient’s chest and the rescuer’s hands that gauge the rate and depth of compression, and invasive devices that measure blood pressure during CPR.
His group is trying to design even better devices, he said. “An example would be a little probe that you could pop on the neck that would study blood flow to the brain with ultrasound, so that while you were pumping on the person, you could see if you’re making them better or not.”
“We also have some preliminary data showing that the American Heart Association recommended position on the chest for doing CPR is not the perfect place for everybody,” he said. The 2020 AHA guidelines recommended the center of the lower half of the sternum. At the 2023 American College of Emergency Physicians meeting, Dr. Becker›s team at Hofstra/Northwell presented data on 175 video-recorded adult cardiac arrests in their emergency department over more than 2 years, 22 of which involved at least one change of compression location (for a total of 29 location changes). They found that 41% of compression location changes were associated with return of spontaneous circulation.
For about a third of people, the hands need to be repositioned slightly. “This is not anything that is taught to the public because you can only figure it out if you have some kind of sensor that will let you know how you’re doing. That’s very achievable. We could have that in the future on every ambulance and even in people’s homes.”
When the person arrives at the hospital, he said, “we can make it easier and more likely that they can be put on extracorporeal membrane oxygenation (ECMO). We do that on selected patients in our hospital, even though it’s very difficult to do, because we know that when it’s done properly, it can change survival rates dramatically, from maybe 10%-50%.”
Dr. Dr. Becker, like Dr. Parnia, also favors the development of drug cocktails, and his team has been experimenting with various combinations in animal models. “We think those two things together — ECMO and a drug cocktail — would be a very powerful one to two knock out for cardiac arrest,” he said. “We have a long way to go — 10 or 20 years. But most people around the world working in this area believe that will be the future.”
Dr. Parnia’s study on recalled death was supported by The John Templeton Foundation, Resuscitation Council (UK), and New York University Grossman School of Medicine, with research support staff provided by the UK’s National Institutes for Health Research. Soar is the editor of the journal Resuscitation and receives payment from the publisher Elsevier. Dr. Becker’s institute has received grants from Philips Medical Systems, NIH, Zoll Medical Corp, Nihon Kohden, PCORI, BrainCool, and United Therapeutics. He has received advisory/consultancy honoraria from NIH, Nihon Kohden, HP, and Philips, and he holds several patents in hypothermia induction and reperfusion therapies and several pending patents involving the use of medical slurries as human coolant devices to create reperfusion cocktails and measurement of respiratory quotient.
A version of this article appeared on Medscape.com.
If someone has been in cardiac arrest for 10 minutes, the brain is permanently damaged and there’s nothing to do, right?
Not so according to emerging evidence that suggests that the brain shows signs of electrical recovery for as long as an hour into ongoing cardiopulmonary resuscitation (CPR). This time between cardiac arrest and awakening can be a period of vivid experiences for the dying patient before they return to life — a phenomenon known as “recalled death.”
This should be an impetus to increase the use of devices that measure the quality of CPR and to find new treatments to restart the heart or prevent brain injury, experts advised. Cardiologists and critical care clinicians are among those who will need to manage patients in the aftermath.
said Jasmeet Soar, MD, consultant in Anesthetics & Intensive Care Medicine, North Bristol NHS Trust, Bristol, England, and an editor of the journal Resuscitation.
“We know that because if chest compressions are stopped, the person becomes unconscious again,” he said. “This CPR-induced consciousness has become more common when professionals do the CPR because resuscitation guidelines now place a much bigger focus on high-quality CPR — ‘push hard, push fast.’ ”
“People are giving up too soon on trying to revive individuals, and they should be trying more modern strategies, such as extracorporeal membrane oxygenation,” said Sam Parnia, MD, PhD, associate professor in the Department of Medicine at NYU Langone Health and director of critical care and resuscitation research at NYU Langone, New York City.
Brain Activity, Heightened Experiences
Two types of brain activity may occur when CPR works. The first, called CPR-induced consciousness, is when an individual recovers consciousness while in cardiac arrest. Signs of consciousness include combativeness, groaning, and eye-opening, Soar explained.
The second type is a perception of lucidity with recall of events, he said. “Patients who experience this may form memories that they can recall. We’re not sure whether that happens during CPR or while the patient is waking up during intensive care, or how the brain creates these memories, or if they’re real memories or coincidental, but it’s clear the brain does form them during the dying and recovery process.”
This latter phenomenon was explored in detail in a recent study led by Dr. Parnia.
In that study of 567 in-hospital patients with cardiac arrest from 25 centers in the United States and United Kingdom, 53 survived, 28 of those survivors were interviewed, and 11 reported memories or perceptions suggestive of consciousness.
Four types of experiences occurred:
- Recalled experiences of death: “I thought I heard my grandma [who had passed] saying ‘you need to go back.’”
- Emergence from coma during CPR/CPR-induced consciousness: “I remember when I came back and they were putting those two electrodes to my chest, and I remember the shock.”
- Emergence from coma in the post-resuscitation period: “I heard my partner saying [patient’s name] and my son saying ‘mom.’”
- Dreams and dream-like experiences: “[I] felt as though someone was holding my hand. It was very black; I couldn’t see anything.”
In a complementary cross-sectional study, 126 community cardiac arrest survivors reported similar experiences plus a fifth type, “delusions,” or “misattribution of medical events,” for example, “I heard my name, over and over again. All around me were things like demons and monsters. It felt like they were trying to tear off my body parts.”
“Many people label recalled experiences of death as ‘near-death’ experiences, but they’re not,” Dr. Parnia said. “Medically speaking, being near to death means your heart is about to stop. But the whole point is that these people are not near death. They actually died and came back from it.”
One of the big implications of the study, he said, is that “a lot of physicians are taught that somehow after, say, 3-5 minutes of oxygen deprivation, the brain dies. Our study showed this is not true. It showed that the brain may not be functioning, which is why they flatline. But if you’re able to resuscitate them appropriately, you can restore activity up to an hour later.”
Because some clinicians questioned or dismissed previous work in this area by Dr. Parnia and others, the latest study used EEG monitoring in a subset of 53 patients. Among those with evaluable EEG data, brain activity returned to normal or near-normal after flatlining in about 40% of images; spikes were seen in the delta (22%), theta (12%), alpha (6%), and beta (1%) waves associated with higher mental function.
“The team recorded what was happening in the brain during real-time CPR using various tests of consciousness, including EEG measurements and tests of visual and auditory awareness using a tablet with a special app and a Bluetooth headphone.”
“Incredibly, we found that even though the brain flatlines, which is what we expect when the heart stops, with professionally given CPR even up to about an hour after this, the brainwaves changed into normal to near-normal patterns,” Dr. Parnia said. “We were able to identify these brain waves in patients while they were being resuscitated, which confirms the fact that people can have lucid consciousness even though they appear to be unconscious.”
Asked what implications, if any, his work has for current definitions of brain death and cardiac death, Dr. Parnia said that the problem is that these are based on the concept of “a permanent irreversible loss of function,” but “that’s only relative to what medical treatments are developed at a given time.”
Potential Mechanism
Dr. Parnia and his team proposed a potential mechanism for recalled experiences of death. Essentially, when the brain flatlines, the dying brain removes natural inhibitory (braking) systems that are needed to support daily functioning. This disinhibition may open access to “new dimensions of reality, including lucid recall of stored memories from early childhood to death,” he said.
From a clinical perspective, he noted, “although the brain stops working when it flatlines, it does not die within 5 or 10 minutes of oxygen deprivation.”
This is contrary to what many doctors believe, and because of that, he said, “nobody has tried to find treatments or new ways to restart the heart or prevent brain injury. They think it’s futile. So, with this work, we’ve opened up the window to developing cocktails of drugs that could be given to patients who have technically gone through death to bring them back to life again.”
Probe Patients or Leave Well Enough Alone?
The findings have ramifications for clinicians who may be caring for patients who survive cardiac arrest, said Lance B. Becker, MD, professor and chair, Department of Emergency Medicine, Donald & Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, New York, and chair, Department of Emergency Medicine at North Shore University Hospital, Manhasset, and Long Island Jewish Medical Center, Queens, New York.
“I’ve talked with a lot of patients who have had some kind of recalled experience around cardiac arrest and some who have had zero recall, as well, like in the paper,” he told this news organization. “The ones who do have an experience are sometimes mystified by it and have questions. And very often, clinicians don’t want to listen, don’t think it’s important, and downplay it.”
“I think it is important, and when people have important things happen to them, it’s really imperative that doctors listen, learn, and respond,” he said. “When I started in this field a long time ago, there were so few survivors that there wasn’t even a concept of survivorship,” he said.
Dr. Becker noted that it’s not uncommon for cardiac arrest survivors to have depression, problems with executive function, or a small brain injury they need to recover from. “Now survivorship organizations are springing up that these people can turn to, but clinicians still need to become more aware and sensitive to this.”
Not all are. “I had a number of patients who said I was the only doctor who ever asked them about what they experienced,” he recalled. “I was a young doctor at the time and didn’t exactly know what to say to them, but they were just happy to have a doctor who would listen to them and not be afraid to hear what they had to say.”
Recognizing that support is an issue, the American Heart Association released a scientific statement in 2020 on sudden cardiac arrest survivorship, which “expands the cardiac arrest resuscitation system of care to include patients, caregivers, and rehabilitative healthcare partnerships, which are central to cardiac survivorship.”
Soar has a more nuanced view of survivorship support, however. “I suspect some people are very glad to be alive, and that trying to dig deep and bring things out may actually be harmful,” he said. “It’s not as clear cut as everybody thinks.”
He noted that follow-up and rehabilitation should be an option for people who specifically need it who would need to be identified. “But human beings are resilient, and while some people will require help, not everybody will,” he said.
Better CPR, New Treatments
Experts in emergency and intensive care medicine studying survival after cardiac arrest hope to find ways to save patients before too much damage is done to the brain and other organs from loss of oxygen, Dr. Parnia said. He is the lead author in a recent multidisciplinary consensus statement on guidelines and standards for the study of death and recalled experiences of death.
“One of my bugbears is that our survival outcomes from cardiac arrest resuscitation have not changed very much for 60 years because we haven’t developed new treatments and innovative methods,” he said. “Unlike the rest of medicine, we’re living in the past.”
Currently, his team is developing cocktails of treatments. These include hypothermic circulatory arrest — cooling the body to stop blood circulation and brain function for up to 40 minutes — and giving magnesium, a brain-protective treatment, to people whose hearts stop.
Dr. Becker would like to see optimal care of patients with cardiac arrest. “The first step is to increase blood flow with good CPR and then measure whether CPR is working,” he said. Adding that despite the availability of devices that provide feedback on the quality of CPR, they’re rarely used. He cited ultrasound devices that measure the blood flow generated during CPR, compression meter devices that go between the patient’s chest and the rescuer’s hands that gauge the rate and depth of compression, and invasive devices that measure blood pressure during CPR.
His group is trying to design even better devices, he said. “An example would be a little probe that you could pop on the neck that would study blood flow to the brain with ultrasound, so that while you were pumping on the person, you could see if you’re making them better or not.”
“We also have some preliminary data showing that the American Heart Association recommended position on the chest for doing CPR is not the perfect place for everybody,” he said. The 2020 AHA guidelines recommended the center of the lower half of the sternum. At the 2023 American College of Emergency Physicians meeting, Dr. Becker›s team at Hofstra/Northwell presented data on 175 video-recorded adult cardiac arrests in their emergency department over more than 2 years, 22 of which involved at least one change of compression location (for a total of 29 location changes). They found that 41% of compression location changes were associated with return of spontaneous circulation.
For about a third of people, the hands need to be repositioned slightly. “This is not anything that is taught to the public because you can only figure it out if you have some kind of sensor that will let you know how you’re doing. That’s very achievable. We could have that in the future on every ambulance and even in people’s homes.”
When the person arrives at the hospital, he said, “we can make it easier and more likely that they can be put on extracorporeal membrane oxygenation (ECMO). We do that on selected patients in our hospital, even though it’s very difficult to do, because we know that when it’s done properly, it can change survival rates dramatically, from maybe 10%-50%.”
Dr. Dr. Becker, like Dr. Parnia, also favors the development of drug cocktails, and his team has been experimenting with various combinations in animal models. “We think those two things together — ECMO and a drug cocktail — would be a very powerful one to two knock out for cardiac arrest,” he said. “We have a long way to go — 10 or 20 years. But most people around the world working in this area believe that will be the future.”
Dr. Parnia’s study on recalled death was supported by The John Templeton Foundation, Resuscitation Council (UK), and New York University Grossman School of Medicine, with research support staff provided by the UK’s National Institutes for Health Research. Soar is the editor of the journal Resuscitation and receives payment from the publisher Elsevier. Dr. Becker’s institute has received grants from Philips Medical Systems, NIH, Zoll Medical Corp, Nihon Kohden, PCORI, BrainCool, and United Therapeutics. He has received advisory/consultancy honoraria from NIH, Nihon Kohden, HP, and Philips, and he holds several patents in hypothermia induction and reperfusion therapies and several pending patents involving the use of medical slurries as human coolant devices to create reperfusion cocktails and measurement of respiratory quotient.
A version of this article appeared on Medscape.com.
How Do Anogenital Injuries Relate to Rape Accusations?
Violence against women by partners is a serious human rights violation and a significant global public health issue. Overall, an estimated 27% of women aged 15-49 years who have been in a relationship have experienced physical or sexual violence (SV) at the hands of a partner. According to 2019 data from the US Department of Justice, SV in the United States occurs every 73 seconds, with child victims every 9 minutes. Lifetime rates of SV are around 17%-18% for women and 3% for men.
The emergency department remains the most common place where patients who have experienced SV seek comprehensive care, including emergency contraception, prophylaxis against sexually transmitted infections, forensic evidence collection for rape cases, and treatment for injuries.
Physical injuries from SV are not always detectable. Studies report variable percentages, ranging from 30%-80% of patients with traumatic SV injuries. Evidence regarding their severity is conflicting.
The presence or absence of anogenital injuries following SV is a factor that can influence both victims’ willingness to report a crime and the judicial decision-making process regarding accusations and convictions.
Rape Myths
The mythology of rape has been under discussion for more than 50 years, encompassing concerns that rape myths reinforce ideas about what does and does not constitute SV and who is a credible victim.
Rape myths, classically defined in the 1980s, are “prejudiced, stereotyped, and false beliefs about rape, rape victims, and rapists,” designed to “deny or minimize perceived harm or blame victims for their victimization.” The concept remains relevant to contemporary societal beliefs and concerns.
A systematic review analyzed elements of rape myths related to victim characteristics and their impact on credibility and blame attribution in the investigative process. Victims who knew the (male) perpetrator and were deemed provocative based on attire were assigned greater blame. In addition, detail and consistency in victims› statements and the presence of physical evidence and injuries increased credibility. However, in certain situations, rape myths may lead to blaming victims who do not fit the “real victim” stereotype, thus resulting in secondary victimization or revictimization.
Anogenital Injuries
Anogenital injuries can occur in relation to consensual sexual activity (CSA), and SV may not be associated with injuries. Therefore, the presence of anogenital injuries does not “prove” SV nor does their absence exclude rape.
This statement is supported by a systematic review and meta-analysis investigating the prevalence of anogenital injuries in women following SV and CSA, using consistent examination techniques for better forensic evidence evaluation in criminal proceedings.
The following two groups were defined for comparison: SV, indicating any nonconsensual sexual contact with the survivor’s anogenital area, and CSA, representing the same type of sexual contact with participants’ consent.
The outcome measure was the presence of anogenital injury (defined as any genital, anal, or perineal injury detected using described techniques in each study). With no universal definition of genital trauma, the result assessment was dichotomous: The presence or absence of injury.
The systematic search yielded 1401 results, and 10 cohort studies published from 1997 to 2022 met the inclusion criteria. The study participants were 3165 women, with 59% (1874/3165) surviving SV.
Anogenital injuries were found in 48% of women who experienced SV (901/1874) and in 31% of those with CSA (394/1291). Anogenital injuries were significantly more likely in women who had experienced SV, compared with those with CSA (risk ratio, 1.59; P < .001). However, both groups had cases where anogenital injuries were either detected or not.
Some SV survivors had no identified anogenital injuries, and women examined after CSA had detectable anogenital injuries. Subgroup analysis for high-quality studies showed no significant differences between groups. These data support the hypothesis that the presence of anogenital injuries does not prove SV, and the absence of injuries does not disprove it.
Point for Practice
Numerous myths reinforce cultural attitudes toward reporting SV. One myth suggests that physical violence, and thus injuries, are inevitable accompaniments to rape. If the victim does not react physically, it might be argued that it was not really rape, or without physical trauma, one might be less inclined to believe that a rape occurred.
Physicians and healthcare professionals involved in the care and support of SV survivors must explicitly reassure them that the lack of anogenital injury evidence does not diminish the credibility of their account.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
Violence against women by partners is a serious human rights violation and a significant global public health issue. Overall, an estimated 27% of women aged 15-49 years who have been in a relationship have experienced physical or sexual violence (SV) at the hands of a partner. According to 2019 data from the US Department of Justice, SV in the United States occurs every 73 seconds, with child victims every 9 minutes. Lifetime rates of SV are around 17%-18% for women and 3% for men.
The emergency department remains the most common place where patients who have experienced SV seek comprehensive care, including emergency contraception, prophylaxis against sexually transmitted infections, forensic evidence collection for rape cases, and treatment for injuries.
Physical injuries from SV are not always detectable. Studies report variable percentages, ranging from 30%-80% of patients with traumatic SV injuries. Evidence regarding their severity is conflicting.
The presence or absence of anogenital injuries following SV is a factor that can influence both victims’ willingness to report a crime and the judicial decision-making process regarding accusations and convictions.
Rape Myths
The mythology of rape has been under discussion for more than 50 years, encompassing concerns that rape myths reinforce ideas about what does and does not constitute SV and who is a credible victim.
Rape myths, classically defined in the 1980s, are “prejudiced, stereotyped, and false beliefs about rape, rape victims, and rapists,” designed to “deny or minimize perceived harm or blame victims for their victimization.” The concept remains relevant to contemporary societal beliefs and concerns.
A systematic review analyzed elements of rape myths related to victim characteristics and their impact on credibility and blame attribution in the investigative process. Victims who knew the (male) perpetrator and were deemed provocative based on attire were assigned greater blame. In addition, detail and consistency in victims› statements and the presence of physical evidence and injuries increased credibility. However, in certain situations, rape myths may lead to blaming victims who do not fit the “real victim” stereotype, thus resulting in secondary victimization or revictimization.
Anogenital Injuries
Anogenital injuries can occur in relation to consensual sexual activity (CSA), and SV may not be associated with injuries. Therefore, the presence of anogenital injuries does not “prove” SV nor does their absence exclude rape.
This statement is supported by a systematic review and meta-analysis investigating the prevalence of anogenital injuries in women following SV and CSA, using consistent examination techniques for better forensic evidence evaluation in criminal proceedings.
The following two groups were defined for comparison: SV, indicating any nonconsensual sexual contact with the survivor’s anogenital area, and CSA, representing the same type of sexual contact with participants’ consent.
The outcome measure was the presence of anogenital injury (defined as any genital, anal, or perineal injury detected using described techniques in each study). With no universal definition of genital trauma, the result assessment was dichotomous: The presence or absence of injury.
The systematic search yielded 1401 results, and 10 cohort studies published from 1997 to 2022 met the inclusion criteria. The study participants were 3165 women, with 59% (1874/3165) surviving SV.
Anogenital injuries were found in 48% of women who experienced SV (901/1874) and in 31% of those with CSA (394/1291). Anogenital injuries were significantly more likely in women who had experienced SV, compared with those with CSA (risk ratio, 1.59; P < .001). However, both groups had cases where anogenital injuries were either detected or not.
Some SV survivors had no identified anogenital injuries, and women examined after CSA had detectable anogenital injuries. Subgroup analysis for high-quality studies showed no significant differences between groups. These data support the hypothesis that the presence of anogenital injuries does not prove SV, and the absence of injuries does not disprove it.
Point for Practice
Numerous myths reinforce cultural attitudes toward reporting SV. One myth suggests that physical violence, and thus injuries, are inevitable accompaniments to rape. If the victim does not react physically, it might be argued that it was not really rape, or without physical trauma, one might be less inclined to believe that a rape occurred.
Physicians and healthcare professionals involved in the care and support of SV survivors must explicitly reassure them that the lack of anogenital injury evidence does not diminish the credibility of their account.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
Violence against women by partners is a serious human rights violation and a significant global public health issue. Overall, an estimated 27% of women aged 15-49 years who have been in a relationship have experienced physical or sexual violence (SV) at the hands of a partner. According to 2019 data from the US Department of Justice, SV in the United States occurs every 73 seconds, with child victims every 9 minutes. Lifetime rates of SV are around 17%-18% for women and 3% for men.
The emergency department remains the most common place where patients who have experienced SV seek comprehensive care, including emergency contraception, prophylaxis against sexually transmitted infections, forensic evidence collection for rape cases, and treatment for injuries.
Physical injuries from SV are not always detectable. Studies report variable percentages, ranging from 30%-80% of patients with traumatic SV injuries. Evidence regarding their severity is conflicting.
The presence or absence of anogenital injuries following SV is a factor that can influence both victims’ willingness to report a crime and the judicial decision-making process regarding accusations and convictions.
Rape Myths
The mythology of rape has been under discussion for more than 50 years, encompassing concerns that rape myths reinforce ideas about what does and does not constitute SV and who is a credible victim.
Rape myths, classically defined in the 1980s, are “prejudiced, stereotyped, and false beliefs about rape, rape victims, and rapists,” designed to “deny or minimize perceived harm or blame victims for their victimization.” The concept remains relevant to contemporary societal beliefs and concerns.
A systematic review analyzed elements of rape myths related to victim characteristics and their impact on credibility and blame attribution in the investigative process. Victims who knew the (male) perpetrator and were deemed provocative based on attire were assigned greater blame. In addition, detail and consistency in victims› statements and the presence of physical evidence and injuries increased credibility. However, in certain situations, rape myths may lead to blaming victims who do not fit the “real victim” stereotype, thus resulting in secondary victimization or revictimization.
Anogenital Injuries
Anogenital injuries can occur in relation to consensual sexual activity (CSA), and SV may not be associated with injuries. Therefore, the presence of anogenital injuries does not “prove” SV nor does their absence exclude rape.
This statement is supported by a systematic review and meta-analysis investigating the prevalence of anogenital injuries in women following SV and CSA, using consistent examination techniques for better forensic evidence evaluation in criminal proceedings.
The following two groups were defined for comparison: SV, indicating any nonconsensual sexual contact with the survivor’s anogenital area, and CSA, representing the same type of sexual contact with participants’ consent.
The outcome measure was the presence of anogenital injury (defined as any genital, anal, or perineal injury detected using described techniques in each study). With no universal definition of genital trauma, the result assessment was dichotomous: The presence or absence of injury.
The systematic search yielded 1401 results, and 10 cohort studies published from 1997 to 2022 met the inclusion criteria. The study participants were 3165 women, with 59% (1874/3165) surviving SV.
Anogenital injuries were found in 48% of women who experienced SV (901/1874) and in 31% of those with CSA (394/1291). Anogenital injuries were significantly more likely in women who had experienced SV, compared with those with CSA (risk ratio, 1.59; P < .001). However, both groups had cases where anogenital injuries were either detected or not.
Some SV survivors had no identified anogenital injuries, and women examined after CSA had detectable anogenital injuries. Subgroup analysis for high-quality studies showed no significant differences between groups. These data support the hypothesis that the presence of anogenital injuries does not prove SV, and the absence of injuries does not disprove it.
Point for Practice
Numerous myths reinforce cultural attitudes toward reporting SV. One myth suggests that physical violence, and thus injuries, are inevitable accompaniments to rape. If the victim does not react physically, it might be argued that it was not really rape, or without physical trauma, one might be less inclined to believe that a rape occurred.
Physicians and healthcare professionals involved in the care and support of SV survivors must explicitly reassure them that the lack of anogenital injury evidence does not diminish the credibility of their account.
This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.
Review Finds No Short-term MACE, VTE risk with JAK Inhibitors For Dermatoses
, at least in the short term, say the authors of a new meta-analysis published in JAMA Dermatology.
Considering data on over 17,000 patients with different dermatoses from 45 placebo-controlled randomized clinical trials with an average follow up of 16 weeks, they found there was no significant increase in the occurrence of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) in people with dermatoses treated with JAK-STAT inhibitors, compared with placebo.
The I² statistic was 0.00% for both MACE and VTE comparing the two arms, indicating that the results were unlikely to be due to chance. There was no increased risk in MACE between those on placebo and those on JAK-STAT inhibitors, with a risk ratio (RR) of 0.47; or for VTE risk, with an RR of 0.46.
Similar findings were obtained when data were analyzed according to the dermatological condition being treated, mechanism of action of the medication, or whether the medication carried a boxed warning.
These data “suggest inconsistency with established sentiments,” that JAK-STAT inhibitors increase the risk for cardiovascular events, Patrick Ireland, MD, of the University of New South Wales, Randwick, Australia, and coauthors wrote in the article. “This may be owing to the limited time frames in which these rare events could be adequately captured, or the ages of enrolled patients being too young to realize the well established heightened risks of developing MACE and VTE,” they suggested.
However, the findings challenge the notion that the cardiovascular complications of these drugs are the same in all patients; dermatological use may not be associated with the same risks as with use for rheumatologic indications.
Class-Wide Boxed Warning
“JAK-STAT [inhibitors] have had some pretty indemnifying data against their use, with the ORAL [Surveillance] study demonstrating increased all-cause mortality, cardiovascular events, venous thromboembolism, and malignancy,” Dr. Ireland said in an interview.
ORAL Surveillance was an open-label, postmarketing trial conducted in patients with rheumatoid arthritis treated with tofacitinib or a tumor necrosis factor (TNF) inhibitor. The results led the US Food and Drug Administration to require information about the risks of serious heart-related events, cancer, blood clots, and death in a boxed warning for JAK-STAT inhibitors in 2022.
“I think it’s important to recognize that these [ORAL Surveillance participants] are very different patients to the typical dermatological patient being treated with a JAK-STAT [inhibitors], with newer studies demonstrating a much safer profile than initially thought,” Dr. Ireland said.
Examining Risk in Dermatological Conditions
The meta-analysis performed by Dr. Ireland and associates focused specifically on the risk for MACE and VTE in patients being treated for dermatological conditions, and included trials published up until June 2023. Only trials that had included a placebo arm were considered; pooled analyses, long-term extension trial data, post hoc analyses, and pediatric-specific trials were excluded.
Most (25) of the trials were phase 2b or phase 3 trials, 18 were phase 2 to 2b, and two were phase 1 trials. The studies included 12,996 participants, mostly with atopic dermatitis or psoriasis, who were treated with JAK-STAT inhibitors, which included baricitinib (2846 patients), tofacitinib (2470), upadacitinib (2218), abrocitinib (1904), and deucravacitinib (1492), among others. There were 4925 patients on placebo.
Overall, MACE — defined as a combined endpoint of acute myocardial infarction, stroke, cardiovascular mortality, heart failure, and unstable angina, as well as arterial embolism — occurred in 13 of the JAK-STAT inhibitor-treated patients and in four of those on placebo. VTE — defined as deep vein thrombosis, pulmonary embolism, and any unusual site thrombosis — was reported in eight JAK-STAT inhibitor-treated patients and in one patient on placebo.
The pooled incidence ratios for MACE and VTE were calculated as 0.20 per 100 person exposure years (PEY) for JAK-STAT inhibitor treatment and 0.13 PEY for placebo. The pooled RRs comparing the two treatment groups were a respective 1.13 for MACE and 2.79 for VTE, but neither RR reached statistical significance.
No difference was seen between the treatment arms in terms of treatment emergent adverse events (RR, 1.05), serious adverse events (RR, 0.92), or study discontinuation because of adverse events (RR, 0.94).
Reassuring Results?
Dr. Ireland and coauthors said the finding should help to reassure clinicians that the short-term use of JAK-STAT inhibitors in patients with dermatological conditions with low cardiovascular risk profiles “appears to be both safe and well tolerated.” They cautioned, however, that “clinicians must remain judicious” when using these medications for longer periods and in high-risk patient populations.
This was a pragmatic meta-analysis that provides useful information for dermatologists, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.
“When there are safety concerns, I think that’s where data like this are so important to not just allay the fears of practitioners, but also to arm the practitioner with information for when they discuss a possible treatment with a patient,” said Dr. Friedman, who was not involved in the study.
“What’s unique here is that they’re looking at any possible use of JAK inhibitors for dermatological disease,” so this represents patients that dermatologists would be seeing, he added.
“The limitation here is time, we only can say so much about the safety of the medication with the data that we have,” Dr. Friedman said. Almost 4 months is “a good amount of time” to know about the cardiovascular risks, he said, but added, what happens then? Will the risk increase and will patients need to be switched to another medication?
“There’s no line in the sand,” with regard to using a JAK-STAT inhibitor. “If you look at the label, they’re not meant to be used incrementally,” but as ongoing treatment, while considering the needs of the patient and the relative risks and benefits, he said.
With that in mind, “the open label extension studies for all these [JAK-STAT inhibitors] are really, really important to get a sense of ‘do new signals emerge down the road.’ ”
The meta-analysis received no commercial funding. One author of the work reported personal fees from several pharmaceutical companies which were done outside of analysis. Dr. Friedman has received research funding from or acted as a consultant for several pharmaceutical companies including, Incyte, Pfizer, Eli Lily, and AbbVie.
, at least in the short term, say the authors of a new meta-analysis published in JAMA Dermatology.
Considering data on over 17,000 patients with different dermatoses from 45 placebo-controlled randomized clinical trials with an average follow up of 16 weeks, they found there was no significant increase in the occurrence of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) in people with dermatoses treated with JAK-STAT inhibitors, compared with placebo.
The I² statistic was 0.00% for both MACE and VTE comparing the two arms, indicating that the results were unlikely to be due to chance. There was no increased risk in MACE between those on placebo and those on JAK-STAT inhibitors, with a risk ratio (RR) of 0.47; or for VTE risk, with an RR of 0.46.
Similar findings were obtained when data were analyzed according to the dermatological condition being treated, mechanism of action of the medication, or whether the medication carried a boxed warning.
These data “suggest inconsistency with established sentiments,” that JAK-STAT inhibitors increase the risk for cardiovascular events, Patrick Ireland, MD, of the University of New South Wales, Randwick, Australia, and coauthors wrote in the article. “This may be owing to the limited time frames in which these rare events could be adequately captured, or the ages of enrolled patients being too young to realize the well established heightened risks of developing MACE and VTE,” they suggested.
However, the findings challenge the notion that the cardiovascular complications of these drugs are the same in all patients; dermatological use may not be associated with the same risks as with use for rheumatologic indications.
Class-Wide Boxed Warning
“JAK-STAT [inhibitors] have had some pretty indemnifying data against their use, with the ORAL [Surveillance] study demonstrating increased all-cause mortality, cardiovascular events, venous thromboembolism, and malignancy,” Dr. Ireland said in an interview.
ORAL Surveillance was an open-label, postmarketing trial conducted in patients with rheumatoid arthritis treated with tofacitinib or a tumor necrosis factor (TNF) inhibitor. The results led the US Food and Drug Administration to require information about the risks of serious heart-related events, cancer, blood clots, and death in a boxed warning for JAK-STAT inhibitors in 2022.
“I think it’s important to recognize that these [ORAL Surveillance participants] are very different patients to the typical dermatological patient being treated with a JAK-STAT [inhibitors], with newer studies demonstrating a much safer profile than initially thought,” Dr. Ireland said.
Examining Risk in Dermatological Conditions
The meta-analysis performed by Dr. Ireland and associates focused specifically on the risk for MACE and VTE in patients being treated for dermatological conditions, and included trials published up until June 2023. Only trials that had included a placebo arm were considered; pooled analyses, long-term extension trial data, post hoc analyses, and pediatric-specific trials were excluded.
Most (25) of the trials were phase 2b or phase 3 trials, 18 were phase 2 to 2b, and two were phase 1 trials. The studies included 12,996 participants, mostly with atopic dermatitis or psoriasis, who were treated with JAK-STAT inhibitors, which included baricitinib (2846 patients), tofacitinib (2470), upadacitinib (2218), abrocitinib (1904), and deucravacitinib (1492), among others. There were 4925 patients on placebo.
Overall, MACE — defined as a combined endpoint of acute myocardial infarction, stroke, cardiovascular mortality, heart failure, and unstable angina, as well as arterial embolism — occurred in 13 of the JAK-STAT inhibitor-treated patients and in four of those on placebo. VTE — defined as deep vein thrombosis, pulmonary embolism, and any unusual site thrombosis — was reported in eight JAK-STAT inhibitor-treated patients and in one patient on placebo.
The pooled incidence ratios for MACE and VTE were calculated as 0.20 per 100 person exposure years (PEY) for JAK-STAT inhibitor treatment and 0.13 PEY for placebo. The pooled RRs comparing the two treatment groups were a respective 1.13 for MACE and 2.79 for VTE, but neither RR reached statistical significance.
No difference was seen between the treatment arms in terms of treatment emergent adverse events (RR, 1.05), serious adverse events (RR, 0.92), or study discontinuation because of adverse events (RR, 0.94).
Reassuring Results?
Dr. Ireland and coauthors said the finding should help to reassure clinicians that the short-term use of JAK-STAT inhibitors in patients with dermatological conditions with low cardiovascular risk profiles “appears to be both safe and well tolerated.” They cautioned, however, that “clinicians must remain judicious” when using these medications for longer periods and in high-risk patient populations.
This was a pragmatic meta-analysis that provides useful information for dermatologists, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.
“When there are safety concerns, I think that’s where data like this are so important to not just allay the fears of practitioners, but also to arm the practitioner with information for when they discuss a possible treatment with a patient,” said Dr. Friedman, who was not involved in the study.
“What’s unique here is that they’re looking at any possible use of JAK inhibitors for dermatological disease,” so this represents patients that dermatologists would be seeing, he added.
“The limitation here is time, we only can say so much about the safety of the medication with the data that we have,” Dr. Friedman said. Almost 4 months is “a good amount of time” to know about the cardiovascular risks, he said, but added, what happens then? Will the risk increase and will patients need to be switched to another medication?
“There’s no line in the sand,” with regard to using a JAK-STAT inhibitor. “If you look at the label, they’re not meant to be used incrementally,” but as ongoing treatment, while considering the needs of the patient and the relative risks and benefits, he said.
With that in mind, “the open label extension studies for all these [JAK-STAT inhibitors] are really, really important to get a sense of ‘do new signals emerge down the road.’ ”
The meta-analysis received no commercial funding. One author of the work reported personal fees from several pharmaceutical companies which were done outside of analysis. Dr. Friedman has received research funding from or acted as a consultant for several pharmaceutical companies including, Incyte, Pfizer, Eli Lily, and AbbVie.
, at least in the short term, say the authors of a new meta-analysis published in JAMA Dermatology.
Considering data on over 17,000 patients with different dermatoses from 45 placebo-controlled randomized clinical trials with an average follow up of 16 weeks, they found there was no significant increase in the occurrence of major adverse cardiovascular events (MACE) or venous thromboembolism (VTE) in people with dermatoses treated with JAK-STAT inhibitors, compared with placebo.
The I² statistic was 0.00% for both MACE and VTE comparing the two arms, indicating that the results were unlikely to be due to chance. There was no increased risk in MACE between those on placebo and those on JAK-STAT inhibitors, with a risk ratio (RR) of 0.47; or for VTE risk, with an RR of 0.46.
Similar findings were obtained when data were analyzed according to the dermatological condition being treated, mechanism of action of the medication, or whether the medication carried a boxed warning.
These data “suggest inconsistency with established sentiments,” that JAK-STAT inhibitors increase the risk for cardiovascular events, Patrick Ireland, MD, of the University of New South Wales, Randwick, Australia, and coauthors wrote in the article. “This may be owing to the limited time frames in which these rare events could be adequately captured, or the ages of enrolled patients being too young to realize the well established heightened risks of developing MACE and VTE,” they suggested.
However, the findings challenge the notion that the cardiovascular complications of these drugs are the same in all patients; dermatological use may not be associated with the same risks as with use for rheumatologic indications.
Class-Wide Boxed Warning
“JAK-STAT [inhibitors] have had some pretty indemnifying data against their use, with the ORAL [Surveillance] study demonstrating increased all-cause mortality, cardiovascular events, venous thromboembolism, and malignancy,” Dr. Ireland said in an interview.
ORAL Surveillance was an open-label, postmarketing trial conducted in patients with rheumatoid arthritis treated with tofacitinib or a tumor necrosis factor (TNF) inhibitor. The results led the US Food and Drug Administration to require information about the risks of serious heart-related events, cancer, blood clots, and death in a boxed warning for JAK-STAT inhibitors in 2022.
“I think it’s important to recognize that these [ORAL Surveillance participants] are very different patients to the typical dermatological patient being treated with a JAK-STAT [inhibitors], with newer studies demonstrating a much safer profile than initially thought,” Dr. Ireland said.
Examining Risk in Dermatological Conditions
The meta-analysis performed by Dr. Ireland and associates focused specifically on the risk for MACE and VTE in patients being treated for dermatological conditions, and included trials published up until June 2023. Only trials that had included a placebo arm were considered; pooled analyses, long-term extension trial data, post hoc analyses, and pediatric-specific trials were excluded.
Most (25) of the trials were phase 2b or phase 3 trials, 18 were phase 2 to 2b, and two were phase 1 trials. The studies included 12,996 participants, mostly with atopic dermatitis or psoriasis, who were treated with JAK-STAT inhibitors, which included baricitinib (2846 patients), tofacitinib (2470), upadacitinib (2218), abrocitinib (1904), and deucravacitinib (1492), among others. There were 4925 patients on placebo.
Overall, MACE — defined as a combined endpoint of acute myocardial infarction, stroke, cardiovascular mortality, heart failure, and unstable angina, as well as arterial embolism — occurred in 13 of the JAK-STAT inhibitor-treated patients and in four of those on placebo. VTE — defined as deep vein thrombosis, pulmonary embolism, and any unusual site thrombosis — was reported in eight JAK-STAT inhibitor-treated patients and in one patient on placebo.
The pooled incidence ratios for MACE and VTE were calculated as 0.20 per 100 person exposure years (PEY) for JAK-STAT inhibitor treatment and 0.13 PEY for placebo. The pooled RRs comparing the two treatment groups were a respective 1.13 for MACE and 2.79 for VTE, but neither RR reached statistical significance.
No difference was seen between the treatment arms in terms of treatment emergent adverse events (RR, 1.05), serious adverse events (RR, 0.92), or study discontinuation because of adverse events (RR, 0.94).
Reassuring Results?
Dr. Ireland and coauthors said the finding should help to reassure clinicians that the short-term use of JAK-STAT inhibitors in patients with dermatological conditions with low cardiovascular risk profiles “appears to be both safe and well tolerated.” They cautioned, however, that “clinicians must remain judicious” when using these medications for longer periods and in high-risk patient populations.
This was a pragmatic meta-analysis that provides useful information for dermatologists, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, said in an interview.
“When there are safety concerns, I think that’s where data like this are so important to not just allay the fears of practitioners, but also to arm the practitioner with information for when they discuss a possible treatment with a patient,” said Dr. Friedman, who was not involved in the study.
“What’s unique here is that they’re looking at any possible use of JAK inhibitors for dermatological disease,” so this represents patients that dermatologists would be seeing, he added.
“The limitation here is time, we only can say so much about the safety of the medication with the data that we have,” Dr. Friedman said. Almost 4 months is “a good amount of time” to know about the cardiovascular risks, he said, but added, what happens then? Will the risk increase and will patients need to be switched to another medication?
“There’s no line in the sand,” with regard to using a JAK-STAT inhibitor. “If you look at the label, they’re not meant to be used incrementally,” but as ongoing treatment, while considering the needs of the patient and the relative risks and benefits, he said.
With that in mind, “the open label extension studies for all these [JAK-STAT inhibitors] are really, really important to get a sense of ‘do new signals emerge down the road.’ ”
The meta-analysis received no commercial funding. One author of the work reported personal fees from several pharmaceutical companies which were done outside of analysis. Dr. Friedman has received research funding from or acted as a consultant for several pharmaceutical companies including, Incyte, Pfizer, Eli Lily, and AbbVie.
FROM JAMA DERMATOLOGY
Top US Oncology Regulator Seeks Changes in Drug Studies
Richard Pazdur, MD, who leads the cancer division at the US Food and Drug Administration (FDA), said there’s a need to simplify the paperwork involved in clinical trials. Before joining the FDA in 1999, Dr. Pazdur participated in and published cancer research. He says the informed consent forms used for studies have grown too elaborate over the years, such that they can intimidate even experts.
“When I read informed consents now in clinical trials, folks, it gives me a headache. Okay, I can’t follow them,” Dr. Pazdur said.
Dr. Pazdur said informed consent forms can be “mind-boggling” these days.
“They’re so damn complicated with so many damn questions being answered,” he said. “So our point is what’s the essential question that you need answered and what’s the quickest way of answering that question with the least amount of data that can be collected?”
Dr. Pazdur made these comments during a joint meeting of the FDA and the European Medicines Agency (EMA).
The meeting was a broad discussion about how to build on the successes seen in treatment of blood cancers in the past two decades. No formal recommendations were introduced or considered at the meeting. Instead, the meeting served as a chance for oncologists and patients to discuss ways to more quickly and efficiently address the key questions in drug research: Do medicines deliver a significant benefit to patients?
Dr. Pazdur also said at the meeting that there needs to be a way to attract more people to enroll in clinical trials.
“When I started in oncology, it was about 5%. When I’m sitting here now, 40 years later, it’s 5%. Basically it hasn’t moved,” he said at the discussion, held on February 1.
Ellin Berman, MD, of Memorial Sloan Kettering Cancer Center in New York, spoke at the meeting about the changes she has witnessed in her career in oncology. Until 2001, there were limited drug options, and physicians tried to get patients to transplant teams as possible. Then the FDA in 2001 approved imatinib to treat patients with chronic myelogenous leukemia (CML) that has the Philadelphia chromosome. That set the stage, Dr. Berman said, for a sea change in treatment of CML.
“The fellows now have no idea what it is like to talk to a CML patient about transplant and the question is which among the treasures we have of drugs do we start people on? And that’s always a conversation,” Dr. Berman said.
She noted that advances in treatment have also let some female patients get pregnant and have children.
“We have at least half a dozen women who bring their kids to clinic. And boy, if that doesn’t bring tears to our eyes, our collective eyes, I don’t know what does,” she said.
Dr. Pazdur also recalled his experience treating patients in the 1970s and 1980s for cancers for which “you had nothing so to speak” in terms of effective treatment.
“So then ask yourself the question, what would their stories be now?” with the many options available, Dr. Pazdur said.
Seeking clinician feedback
To try to improve the development and testing of cancer drugs, the FDA is seeking to get more feedback from clinicians about which questions trials should address, Dr. Pazdur said.
The agency is considering a way to poll clinicians on what their most crucial questions are about the medicines, he said. Better design of trial questions might serve to improve enrollment in studies.
“What we’re thinking of doing is taking the common disease areas and asking clinicians what are the five basic questions that you want answered in the next 5 years,” he said.
He cited PD-1 drugs as a possible example of a class where regulators could consider new approaches. There could be a discussion about the safety data collection for this class of drugs, which has been used by millions of patients.
Dr. Pazdur said he has been discussing these kinds of themes with his European and Japanese counterparts, who also are interested in simplifying clinical trials.
The goal is to have trials better represent real-world experiences rather than “artificial” ones created when patients must meet extensive eligibility requirements. Improved use of emerging technologies could aid in the needed streamlining, Dr. Pazdur said.
“As an oncology community, we have made our lives somewhat too complicated and need to draw back and ask the basic questions,” Dr. Pazdur said.
Richard Pazdur, MD, who leads the cancer division at the US Food and Drug Administration (FDA), said there’s a need to simplify the paperwork involved in clinical trials. Before joining the FDA in 1999, Dr. Pazdur participated in and published cancer research. He says the informed consent forms used for studies have grown too elaborate over the years, such that they can intimidate even experts.
“When I read informed consents now in clinical trials, folks, it gives me a headache. Okay, I can’t follow them,” Dr. Pazdur said.
Dr. Pazdur said informed consent forms can be “mind-boggling” these days.
“They’re so damn complicated with so many damn questions being answered,” he said. “So our point is what’s the essential question that you need answered and what’s the quickest way of answering that question with the least amount of data that can be collected?”
Dr. Pazdur made these comments during a joint meeting of the FDA and the European Medicines Agency (EMA).
The meeting was a broad discussion about how to build on the successes seen in treatment of blood cancers in the past two decades. No formal recommendations were introduced or considered at the meeting. Instead, the meeting served as a chance for oncologists and patients to discuss ways to more quickly and efficiently address the key questions in drug research: Do medicines deliver a significant benefit to patients?
Dr. Pazdur also said at the meeting that there needs to be a way to attract more people to enroll in clinical trials.
“When I started in oncology, it was about 5%. When I’m sitting here now, 40 years later, it’s 5%. Basically it hasn’t moved,” he said at the discussion, held on February 1.
Ellin Berman, MD, of Memorial Sloan Kettering Cancer Center in New York, spoke at the meeting about the changes she has witnessed in her career in oncology. Until 2001, there were limited drug options, and physicians tried to get patients to transplant teams as possible. Then the FDA in 2001 approved imatinib to treat patients with chronic myelogenous leukemia (CML) that has the Philadelphia chromosome. That set the stage, Dr. Berman said, for a sea change in treatment of CML.
“The fellows now have no idea what it is like to talk to a CML patient about transplant and the question is which among the treasures we have of drugs do we start people on? And that’s always a conversation,” Dr. Berman said.
She noted that advances in treatment have also let some female patients get pregnant and have children.
“We have at least half a dozen women who bring their kids to clinic. And boy, if that doesn’t bring tears to our eyes, our collective eyes, I don’t know what does,” she said.
Dr. Pazdur also recalled his experience treating patients in the 1970s and 1980s for cancers for which “you had nothing so to speak” in terms of effective treatment.
“So then ask yourself the question, what would their stories be now?” with the many options available, Dr. Pazdur said.
Seeking clinician feedback
To try to improve the development and testing of cancer drugs, the FDA is seeking to get more feedback from clinicians about which questions trials should address, Dr. Pazdur said.
The agency is considering a way to poll clinicians on what their most crucial questions are about the medicines, he said. Better design of trial questions might serve to improve enrollment in studies.
“What we’re thinking of doing is taking the common disease areas and asking clinicians what are the five basic questions that you want answered in the next 5 years,” he said.
He cited PD-1 drugs as a possible example of a class where regulators could consider new approaches. There could be a discussion about the safety data collection for this class of drugs, which has been used by millions of patients.
Dr. Pazdur said he has been discussing these kinds of themes with his European and Japanese counterparts, who also are interested in simplifying clinical trials.
The goal is to have trials better represent real-world experiences rather than “artificial” ones created when patients must meet extensive eligibility requirements. Improved use of emerging technologies could aid in the needed streamlining, Dr. Pazdur said.
“As an oncology community, we have made our lives somewhat too complicated and need to draw back and ask the basic questions,” Dr. Pazdur said.
Richard Pazdur, MD, who leads the cancer division at the US Food and Drug Administration (FDA), said there’s a need to simplify the paperwork involved in clinical trials. Before joining the FDA in 1999, Dr. Pazdur participated in and published cancer research. He says the informed consent forms used for studies have grown too elaborate over the years, such that they can intimidate even experts.
“When I read informed consents now in clinical trials, folks, it gives me a headache. Okay, I can’t follow them,” Dr. Pazdur said.
Dr. Pazdur said informed consent forms can be “mind-boggling” these days.
“They’re so damn complicated with so many damn questions being answered,” he said. “So our point is what’s the essential question that you need answered and what’s the quickest way of answering that question with the least amount of data that can be collected?”
Dr. Pazdur made these comments during a joint meeting of the FDA and the European Medicines Agency (EMA).
The meeting was a broad discussion about how to build on the successes seen in treatment of blood cancers in the past two decades. No formal recommendations were introduced or considered at the meeting. Instead, the meeting served as a chance for oncologists and patients to discuss ways to more quickly and efficiently address the key questions in drug research: Do medicines deliver a significant benefit to patients?
Dr. Pazdur also said at the meeting that there needs to be a way to attract more people to enroll in clinical trials.
“When I started in oncology, it was about 5%. When I’m sitting here now, 40 years later, it’s 5%. Basically it hasn’t moved,” he said at the discussion, held on February 1.
Ellin Berman, MD, of Memorial Sloan Kettering Cancer Center in New York, spoke at the meeting about the changes she has witnessed in her career in oncology. Until 2001, there were limited drug options, and physicians tried to get patients to transplant teams as possible. Then the FDA in 2001 approved imatinib to treat patients with chronic myelogenous leukemia (CML) that has the Philadelphia chromosome. That set the stage, Dr. Berman said, for a sea change in treatment of CML.
“The fellows now have no idea what it is like to talk to a CML patient about transplant and the question is which among the treasures we have of drugs do we start people on? And that’s always a conversation,” Dr. Berman said.
She noted that advances in treatment have also let some female patients get pregnant and have children.
“We have at least half a dozen women who bring their kids to clinic. And boy, if that doesn’t bring tears to our eyes, our collective eyes, I don’t know what does,” she said.
Dr. Pazdur also recalled his experience treating patients in the 1970s and 1980s for cancers for which “you had nothing so to speak” in terms of effective treatment.
“So then ask yourself the question, what would their stories be now?” with the many options available, Dr. Pazdur said.
Seeking clinician feedback
To try to improve the development and testing of cancer drugs, the FDA is seeking to get more feedback from clinicians about which questions trials should address, Dr. Pazdur said.
The agency is considering a way to poll clinicians on what their most crucial questions are about the medicines, he said. Better design of trial questions might serve to improve enrollment in studies.
“What we’re thinking of doing is taking the common disease areas and asking clinicians what are the five basic questions that you want answered in the next 5 years,” he said.
He cited PD-1 drugs as a possible example of a class where regulators could consider new approaches. There could be a discussion about the safety data collection for this class of drugs, which has been used by millions of patients.
Dr. Pazdur said he has been discussing these kinds of themes with his European and Japanese counterparts, who also are interested in simplifying clinical trials.
The goal is to have trials better represent real-world experiences rather than “artificial” ones created when patients must meet extensive eligibility requirements. Improved use of emerging technologies could aid in the needed streamlining, Dr. Pazdur said.
“As an oncology community, we have made our lives somewhat too complicated and need to draw back and ask the basic questions,” Dr. Pazdur said.
Success with Sirolimus in Treating Skin Sarcoidosis Could Spur Studies in Other Organs
Sirolimus may be an effective treatment for patients with persistent cutaneous sarcoidosis.
In a small clinical trial, 7 of 10 patients treated with sirolimus via oral solution had improvements in skin lesions after 4 months, which was sustained for up to 2 years after the study concluded.
The results suggested that mechanistic target of rapamycin (mTOR) inhibition is a potential therapeutic avenue for sarcoidosis, which the authors said should be explored in larger clinical trials.
In the past decade, there has been a growing amount of evidence suggesting mTOR’s role in sarcoidosis. In 2017, researchers showed that activation of mTOR in macrophages could cause progressive sarcoidosis in mice. In additional studies, high levels of mTOR activity were detected in human sarcoidosis granulomas in various organs, including the skin, lung, and heart.
Three case reports also documented using the mTOR inhibitor sirolimus to effectively treat systemic sarcoidosis.
“Although all reports observed improvement of the disease following the treatment, no clinical trial investigating the efficacy and safety of sirolimus in patients with sarcoidosis had been published” prior to this study, wrote senior author Georg Stary, MD, of the Medical University of Vienna and the Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria, and colleagues.
The findings were published in the The Lancet Rheumatology.
For the study, researchers recruited 16 individuals with persistent and glucocorticoid-refractory cutaneous sarcoidosis between September 2019 and June 2021. A total of 14 participants were randomly assigned to the topical phase of the study, whereas two immediately received systemic treatment. All treatment was conducted at Vienna General Hospital.
In the placebo-controlled, double-blinded topical treatment arm, patients received either 0.1% topical sirolimus in Vaseline or Vaseline alone (placebo) twice daily for 2 months. After a 1-month washout period, participants were switched to the alternate treatment arm for an additional 2 months.
Following this topical phase and an additional 1-month washout period, all remaining participants received systemic sirolimus via a 1-mg/mL solution, starting with a 6-mg loading dose and continuing with 2 mg once daily for 4 months. The primary outcome was change in Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) from baseline, with decrease of more than five points representing a response to treatment.
A total of 10 patients completed the trial.
There was no change in CSAMI in either topical treatment groups. In the systemic group, 70% of patients had clinical improvement in skin lesions, with three responders in this group having complete resolution of skin lesions. The median change in CSAMI was −7.0 points (P = .018).
This improvement persisted for 2 months following study conclusion, with more pronounced improvement from baseline after 2 years of drug-free follow-up (−11.5 points).
There were no serious adverse events reported during the study, but 42% of patients treated with systemic sirolimus reported mild skin reactions, such as acne and eczema. Other related adverse events were hypertriglyceridemia (17%), hyperglycemia (17%), and proteinuria (8%).
Compared with clinical outcomes with tofacitinib and tumor necrosis factor (TNF) inhibitors, “the strength of our study lies in the sustained treatment effect after drug withdrawal among all responders. This prolonged effect has not yet been explored with tofacitinib, whereas with TNF inhibitors disease relapse was seen in more than 50% of patients at 3-8 months,” the authors wrote.
The researchers also analyzed participants’ skin biopsies to gain a better understanding of how mTOR inhibition affected granuloma structures. They found that, at baseline, mTOR activity was significantly lower in the fibroblasts of treatment nonresponders than in responders. They speculated that lower expression of mTOR could make these granuloma-associated cells resistant to systemic sirolimus.
These promising findings combine “clinical response with a molecular analysis,” Avrom Caplan, MD, co-director of the Sarcoidosis Program at NYU Langone in New York City, told this news organization. He was not involved with the research. Adding molecular information to clinical outcome data “helps solidify that [the mTOR] pathway has relevance in the sarcoid granuloma formation.”
The study had a limited sample size — a challenge for many clinical trials of rare diseases, Dr. Caplan said. Larger clinical trials are necessary to explore mTOR inhibition in sarcoidosis, both he and the authors agreed. A larger trial could also include greater heterogeneity of patients, including varied sarcoid presentation and demographics, Dr. Caplan noted. In this study, all but one participants were White individuals, and 63% of participants were female.
Larger studies could also address important questions on ideal length of therapy, dosing, and where this therapy “would fall within the therapeutic step ladder,” Dr. Caplan continued.
Whether mTOR inhibition could be effective at treating individuals with sarcoidosis in other organs beyond the skin is also unknown.
“If the pathogenesis of sarcoid granuloma formation does include mTOR upregulation, which they are showing here…then you could hypothesize that, yes, using this therapy could benefit other organs,” he said. “But that has to be investigated in larger trials.”
The study was funded in part by a Vienna Science and Technology Fund project. Several authors report receiving grants from the Austrian Science Fund and one from the Ann Theodore Foundation Breakthrough Sarcoidosis Initiative. Dr. Caplan reported no relevant financial relationships.
A version of this article appeared on Medscape.com .
Sirolimus may be an effective treatment for patients with persistent cutaneous sarcoidosis.
In a small clinical trial, 7 of 10 patients treated with sirolimus via oral solution had improvements in skin lesions after 4 months, which was sustained for up to 2 years after the study concluded.
The results suggested that mechanistic target of rapamycin (mTOR) inhibition is a potential therapeutic avenue for sarcoidosis, which the authors said should be explored in larger clinical trials.
In the past decade, there has been a growing amount of evidence suggesting mTOR’s role in sarcoidosis. In 2017, researchers showed that activation of mTOR in macrophages could cause progressive sarcoidosis in mice. In additional studies, high levels of mTOR activity were detected in human sarcoidosis granulomas in various organs, including the skin, lung, and heart.
Three case reports also documented using the mTOR inhibitor sirolimus to effectively treat systemic sarcoidosis.
“Although all reports observed improvement of the disease following the treatment, no clinical trial investigating the efficacy and safety of sirolimus in patients with sarcoidosis had been published” prior to this study, wrote senior author Georg Stary, MD, of the Medical University of Vienna and the Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria, and colleagues.
The findings were published in the The Lancet Rheumatology.
For the study, researchers recruited 16 individuals with persistent and glucocorticoid-refractory cutaneous sarcoidosis between September 2019 and June 2021. A total of 14 participants were randomly assigned to the topical phase of the study, whereas two immediately received systemic treatment. All treatment was conducted at Vienna General Hospital.
In the placebo-controlled, double-blinded topical treatment arm, patients received either 0.1% topical sirolimus in Vaseline or Vaseline alone (placebo) twice daily for 2 months. After a 1-month washout period, participants were switched to the alternate treatment arm for an additional 2 months.
Following this topical phase and an additional 1-month washout period, all remaining participants received systemic sirolimus via a 1-mg/mL solution, starting with a 6-mg loading dose and continuing with 2 mg once daily for 4 months. The primary outcome was change in Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) from baseline, with decrease of more than five points representing a response to treatment.
A total of 10 patients completed the trial.
There was no change in CSAMI in either topical treatment groups. In the systemic group, 70% of patients had clinical improvement in skin lesions, with three responders in this group having complete resolution of skin lesions. The median change in CSAMI was −7.0 points (P = .018).
This improvement persisted for 2 months following study conclusion, with more pronounced improvement from baseline after 2 years of drug-free follow-up (−11.5 points).
There were no serious adverse events reported during the study, but 42% of patients treated with systemic sirolimus reported mild skin reactions, such as acne and eczema. Other related adverse events were hypertriglyceridemia (17%), hyperglycemia (17%), and proteinuria (8%).
Compared with clinical outcomes with tofacitinib and tumor necrosis factor (TNF) inhibitors, “the strength of our study lies in the sustained treatment effect after drug withdrawal among all responders. This prolonged effect has not yet been explored with tofacitinib, whereas with TNF inhibitors disease relapse was seen in more than 50% of patients at 3-8 months,” the authors wrote.
The researchers also analyzed participants’ skin biopsies to gain a better understanding of how mTOR inhibition affected granuloma structures. They found that, at baseline, mTOR activity was significantly lower in the fibroblasts of treatment nonresponders than in responders. They speculated that lower expression of mTOR could make these granuloma-associated cells resistant to systemic sirolimus.
These promising findings combine “clinical response with a molecular analysis,” Avrom Caplan, MD, co-director of the Sarcoidosis Program at NYU Langone in New York City, told this news organization. He was not involved with the research. Adding molecular information to clinical outcome data “helps solidify that [the mTOR] pathway has relevance in the sarcoid granuloma formation.”
The study had a limited sample size — a challenge for many clinical trials of rare diseases, Dr. Caplan said. Larger clinical trials are necessary to explore mTOR inhibition in sarcoidosis, both he and the authors agreed. A larger trial could also include greater heterogeneity of patients, including varied sarcoid presentation and demographics, Dr. Caplan noted. In this study, all but one participants were White individuals, and 63% of participants were female.
Larger studies could also address important questions on ideal length of therapy, dosing, and where this therapy “would fall within the therapeutic step ladder,” Dr. Caplan continued.
Whether mTOR inhibition could be effective at treating individuals with sarcoidosis in other organs beyond the skin is also unknown.
“If the pathogenesis of sarcoid granuloma formation does include mTOR upregulation, which they are showing here…then you could hypothesize that, yes, using this therapy could benefit other organs,” he said. “But that has to be investigated in larger trials.”
The study was funded in part by a Vienna Science and Technology Fund project. Several authors report receiving grants from the Austrian Science Fund and one from the Ann Theodore Foundation Breakthrough Sarcoidosis Initiative. Dr. Caplan reported no relevant financial relationships.
A version of this article appeared on Medscape.com .
Sirolimus may be an effective treatment for patients with persistent cutaneous sarcoidosis.
In a small clinical trial, 7 of 10 patients treated with sirolimus via oral solution had improvements in skin lesions after 4 months, which was sustained for up to 2 years after the study concluded.
The results suggested that mechanistic target of rapamycin (mTOR) inhibition is a potential therapeutic avenue for sarcoidosis, which the authors said should be explored in larger clinical trials.
In the past decade, there has been a growing amount of evidence suggesting mTOR’s role in sarcoidosis. In 2017, researchers showed that activation of mTOR in macrophages could cause progressive sarcoidosis in mice. In additional studies, high levels of mTOR activity were detected in human sarcoidosis granulomas in various organs, including the skin, lung, and heart.
Three case reports also documented using the mTOR inhibitor sirolimus to effectively treat systemic sarcoidosis.
“Although all reports observed improvement of the disease following the treatment, no clinical trial investigating the efficacy and safety of sirolimus in patients with sarcoidosis had been published” prior to this study, wrote senior author Georg Stary, MD, of the Medical University of Vienna and the Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria, and colleagues.
The findings were published in the The Lancet Rheumatology.
For the study, researchers recruited 16 individuals with persistent and glucocorticoid-refractory cutaneous sarcoidosis between September 2019 and June 2021. A total of 14 participants were randomly assigned to the topical phase of the study, whereas two immediately received systemic treatment. All treatment was conducted at Vienna General Hospital.
In the placebo-controlled, double-blinded topical treatment arm, patients received either 0.1% topical sirolimus in Vaseline or Vaseline alone (placebo) twice daily for 2 months. After a 1-month washout period, participants were switched to the alternate treatment arm for an additional 2 months.
Following this topical phase and an additional 1-month washout period, all remaining participants received systemic sirolimus via a 1-mg/mL solution, starting with a 6-mg loading dose and continuing with 2 mg once daily for 4 months. The primary outcome was change in Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) from baseline, with decrease of more than five points representing a response to treatment.
A total of 10 patients completed the trial.
There was no change in CSAMI in either topical treatment groups. In the systemic group, 70% of patients had clinical improvement in skin lesions, with three responders in this group having complete resolution of skin lesions. The median change in CSAMI was −7.0 points (P = .018).
This improvement persisted for 2 months following study conclusion, with more pronounced improvement from baseline after 2 years of drug-free follow-up (−11.5 points).
There were no serious adverse events reported during the study, but 42% of patients treated with systemic sirolimus reported mild skin reactions, such as acne and eczema. Other related adverse events were hypertriglyceridemia (17%), hyperglycemia (17%), and proteinuria (8%).
Compared with clinical outcomes with tofacitinib and tumor necrosis factor (TNF) inhibitors, “the strength of our study lies in the sustained treatment effect after drug withdrawal among all responders. This prolonged effect has not yet been explored with tofacitinib, whereas with TNF inhibitors disease relapse was seen in more than 50% of patients at 3-8 months,” the authors wrote.
The researchers also analyzed participants’ skin biopsies to gain a better understanding of how mTOR inhibition affected granuloma structures. They found that, at baseline, mTOR activity was significantly lower in the fibroblasts of treatment nonresponders than in responders. They speculated that lower expression of mTOR could make these granuloma-associated cells resistant to systemic sirolimus.
These promising findings combine “clinical response with a molecular analysis,” Avrom Caplan, MD, co-director of the Sarcoidosis Program at NYU Langone in New York City, told this news organization. He was not involved with the research. Adding molecular information to clinical outcome data “helps solidify that [the mTOR] pathway has relevance in the sarcoid granuloma formation.”
The study had a limited sample size — a challenge for many clinical trials of rare diseases, Dr. Caplan said. Larger clinical trials are necessary to explore mTOR inhibition in sarcoidosis, both he and the authors agreed. A larger trial could also include greater heterogeneity of patients, including varied sarcoid presentation and demographics, Dr. Caplan noted. In this study, all but one participants were White individuals, and 63% of participants were female.
Larger studies could also address important questions on ideal length of therapy, dosing, and where this therapy “would fall within the therapeutic step ladder,” Dr. Caplan continued.
Whether mTOR inhibition could be effective at treating individuals with sarcoidosis in other organs beyond the skin is also unknown.
“If the pathogenesis of sarcoid granuloma formation does include mTOR upregulation, which they are showing here…then you could hypothesize that, yes, using this therapy could benefit other organs,” he said. “But that has to be investigated in larger trials.”
The study was funded in part by a Vienna Science and Technology Fund project. Several authors report receiving grants from the Austrian Science Fund and one from the Ann Theodore Foundation Breakthrough Sarcoidosis Initiative. Dr. Caplan reported no relevant financial relationships.
A version of this article appeared on Medscape.com .
FROM THE LANCET RHEUMATOLOGY
CHIP Tied to HFpEF and ASCVD: What’s the Link?
A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).
But what exactly is CHIP, and what is its potential value in CVD risk and management?
CHIP is estimated to affect about 10% of people aged 70 years and older.
First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.
CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.
“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.
Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.
To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).
In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.
“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.
In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.
Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”
He cautioned, however, that the findings need to be validated in other studies.
“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.
Targeted Treatment?
Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.
Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.
For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.
“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.
“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.
“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.
“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added.
Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
A version of this article appeared on Medscape.com.
A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).
But what exactly is CHIP, and what is its potential value in CVD risk and management?
CHIP is estimated to affect about 10% of people aged 70 years and older.
First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.
CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.
“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.
Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.
To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).
In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.
“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.
In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.
Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”
He cautioned, however, that the findings need to be validated in other studies.
“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.
Targeted Treatment?
Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.
Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.
For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.
“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.
“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.
“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.
“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added.
Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
A version of this article appeared on Medscape.com.
A new study added heart failure with preserved ejection fraction (HFpEF) to the growing list of cardiovascular conditions linked to clonal hematopoiesis of indeterminate potential (CHIP), which already includes atherosclerotic cardiovascular disease (ASCVD).
But what exactly is CHIP, and what is its potential value in CVD risk and management?
CHIP is estimated to affect about 10% of people aged 70 years and older.
First described as a risk factor for hematologic, particularly myeloid, malignant neoplasms, CHIP has recently emerged as a novel CVD risk factor.
CHIP gives rise to proinflammatory immune cells, which can exacerbate ASCVD and may induce or accelerate HF.
“The association between CHIP and HFpEF may be particularly relevant, given that the prevalence of HFpEF is rising due to the progressive aging of the population,” said José J. Fuster, PhD, coordinator for the program on novel mechanisms of atherosclerosis, Spanish National Center for Cardiovascular Research, Madrid.
Yet previous studies examining CHIP and HF have either focused on overall HF without distinguishing HF subtypes of preserved vs reduced ejection fraction, or have examined its prognostic significance in the setting of established HF, rather than the development of future HF.
To help fill the gap, Boston-based researchers recently evaluated associations of CHIP and the two most common gene-specific CHIP subtypes (TET2 and DNMT3A CHIP) with incident HFpEF and HF with reduced ejection fraction (HFrEF).
In two racially diverse cohorts with a total of 8090 adults, TET2 CHIP was independently associated with > twofold higher risk of incident HFpEF. By contrast, there were no significant associations of CHIP with incident HFrEF.
“Our study’s fundings suggest that previously described associations between CHIP and future development of heart failure may be driven primarily by HFpEF,” said Michael Honigberg, MD, with the Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston.
In addition, the “clearest signal for an association with HF was observed for TET2 CHIP, the second-most common subtype of CHIP in the population. This finding aligns with a recently published study that reported relative enrichment of TET2 CHIP in a small human HFpEF cohort,” Dr. Honigberg said.
Dr. Fuster said the connection between CHIP and aging “enhances the potential clinical relevance of this study, as CHIP is frequent in elderly individuals and, therefore, may contribute to the pathophysiology of HFpEF in a high proportion of patients.”
He cautioned, however, that the findings need to be validated in other studies.
“In addition, there is a growing recognition that the effects of CHIP are heterogeneous, as mutations in different genes have different effects on cardiovascular and act through different mechanisms. Additional studies will be needed to dissect gene-specific effects in HFpEF. It will also be important to explore whether CHIP influences the clinical progression of the disease,” Dr. Fuster said.
Targeted Treatment?
Dr. Honigberg said the findings may aid in the development of new targeted-treatment strategies for at least the subset of patients with HFpEF.
Based on multiple lines of evidence, the mechanism linking TET2 CHIP to CVD appears to be heightened inflammation, he explained.
For example, in a substudy of the CANTOS trial, patients with atherosclerosis and TET2 CHIP who received canakinumab appeared to derive “outsized benefit” in preventing CV events compared with the overall trial population, Dr. Honigberg said.
“HFpEF is a particularly challenging disease with limited effective therapies. Our findings support the premise that targeted anti-inflammatory therapies may prevent and/or treat HFpEF driven by TET2 CHIP. Of course, this hypothesis will require testing in prospective randomized trials,” Dr. Honigberg said.
“The field of CHIP has developed rapidly, and it is an exciting area of research,” Dr. Fuster added. “However, I personally believe that much work lies ahead before it is ready for prime time in the clinical setting.
“Although the link between CHIP and CVD is solid, we still lack evidence-based interventions to mitigate the elevated CVD risk associated with these mutations. In the absence of effective interventions, the added value of screening for CHIP as a risk factor may be limited,” Dr. Fuster noted.
“For instance, in the setting of HFpEF, we don’t really know whether CHIP mutation carriers may respond favorably to contemporary HF medications or may require new personalized approaches. Additional research and, eventually, clinical trials, are needed,” he added.
Dr. Honigberg has disclosed relationships with Genentech, Miga Health, CRISPR Therapeutics, and Comanche Biopharma. Dr. Fuster has no relevant disclosures.
A version of this article appeared on Medscape.com.
The Impact of a Paracentesis Clinic on Internal Medicine Resident Procedural Competency
Competency in paracentesis is an important procedural skill for medical practitioners caring for patients with decompensated liver cirrhosis. Paracentesis is performed to drain ascitic fluid for both diagnosis and/or therapeutic purposes.1 While this procedure can be performed without the use of ultrasound, it is preferable to use ultrasound to identify an area of fluid that is away from dangerous anatomy including bowel loops, the liver, and spleen. After prepping the area, lidocaine is administered locally. A catheter is then inserted until fluid begins flowing freely. The catheter is connected to a suction canister or collection kit, and the patient is monitored until the flow ceases. Samples can be sent for analysis to determine the etiology of ascites, identify concerns for infection, and more.
Paracentesis is a very common procedure. Barsuk and colleagues noted that between 2010 and 2012, 97,577 procedures were performed across 120 academic medical centers and 290 affiliated hospitals.2 Patients undergo paracentesis in a variety of settings including the emergency department, inpatient hospitalizations, and clinics. Some patients may require only 1 paracentesis procedure while others may require it regularly.
Due to the rising need for paracentesis in the Central Texas Veterans Affairs Hospital (CTVAH) in Temple, a paracentesis clinic was started in February 2018. The goal of the paracentesis clinic was multifocal—to reduce hospital admissions, improve access to regularly scheduled procedures, decrease wait times, and increase patient satisfaction.3 Through the CTVAH affiliation with the Texas A&M internal medicine residency program, the paracentesis clinic started involving and training residents on this procedure. Up to 3 residents are on weekly rotation and can perform up to 6 paracentesis procedures in a week. The purpose of this article was to evaluate resident competency in paracentesis after completion of the paracentesis clinic.
Methods
The paracentesis clinic schedules up to 3 patients on Tuesdays and Thursdays between 8
A survey was sent via email to all categorical internal medicine residents across all 3 program years at the time of data collection. Competency for paracentesis sign-off was defined as completing and logging 5 procedures supervised by a competent physician who confirmed that all portions of the procedure were performed correctly. Residents were also asked to answer questions on a scale from 1 to 10, with 1 representing no confidence and 10 representing strong confidence to practice independently (Table).
We also evaluated the number of procedures performed by internal medicine residents 3 years before the clinic was started in 2015 up to the completion of 2022. The numbers were obtained by examining procedural log data for each year for all internal medicine residents.
Results
Thirty-three residents completed the survey: 10 first-year internal medicine residents (PGY1), 12 second-year residents (PGY2), and 11 third-year residents (PGY3). The mean participation was 4.8 paracentesis sessions per person for the duration of the study. The range of paracentesis procedures performed varied based on PGY year: PGY1s performed 1 to > 10 procedures, PGY2s performed 2 to > 10 procedures, and PGY3s performed 5 to > 10 procedures. Thirty-six percent of residents completed > 10 procedures in the paracentesis clinic; 82% of PGY3s had completed > 10 procedures by December of their third year. Twenty-six residents (79%) were credentialed to perform paracentesis procedures independently after performing > 5 procedures, and 7 residents were not yet cleared for procedural independence.
In the survey, residents rated their comfort with performing paracentesis procedures independently at a mean of 7.9. The mean comfort reported by PGY1s was 7.2, PGY2s was 7.3, and PGY3s was 9.3. Residents also rated their opinion on whether or not the paracentesis clinic adequately prepared them for paracentesis procedural independence; the mean was 8.9 across all residents.
The total number of procedures performed by residents at CTVAH also increased. Starting in 2015, 3 years before the clinic was started, 38 procedures were performed by internal medicine residents, followed by 72 procedures in 2016; 76 in 2017; 58 in 2018; 94 in 2019; 88 in 2020; 136 in 2021; and 188 in 2022.
Discussion
Paracentesis is a simple but invasive procedure to relieve ascites, often relieving patients’ symptoms, preventing hospital admission, and increasing patient satisfaction.4 The CTVAH does not have the capacity to perform outpatient paracentesis effectively in its emergency or radiology departments. Furthermore, the use of the emergency or radiology departments for routine paracentesis may not be feasible due to the acuity of care being provided, as these procedures can be time consuming and can draw away critical resources and time from patients that need emergent care. The paracentesis clinic was then formed to provide veterans access to the procedural care they need, while also preparing residents to ably and confidently perform the procedure independently.
Based on our study, most residents were cleared to independently perform paracentesis procedures across all 3 years, with 79% of residents having completed the required 5 supervised procedures to independently practice. A study assessing unsupervised practice standards showed that paracentesis skill declines as soon as 3 months after training. However, retraining was shown to potentially interrupt this skill decline.5 Studies have shown that procedure-driven electives or services significantly improved paracentesis certification rates and total logged procedures, with minimal funding or scheduling changes required.6 Our clinic showed a significant increase in the number of procedures logged starting with the minimum of 38 procedures in 2015 and ending with 188 procedures logged at the end of 2022.
By allowing residents to routinely return to the paracentesis clinic across all 3 years, residents were more likely to feel comfortable independently performing the procedure, with residents reporting a mean comfort score of 7.9. The spaced repetition and ability to work with the clinic during elective time allows regular opportunities to undergo supervised training in a controlled environment and created scheduled retraining opportunities. Future studies should evaluate residents prior to each paracentesis clinic to ascertain if skill decline is occurring at a slower rate.
The inpatient effect of the clinic is also multifocal. Pham and colleagues showed that integrating paracentesis into timely training can reduce paracentesis delay and delays in care.7 By increasing the volume of procedures each resident performs and creating a sense of confidence amongst residents, the clinic increases the number of residents able and willing to perform inpatient procedures, thus reducing the number of unnecessary consultations and hospital resources. One of the reasons the paracentesis clinic was started was to allow patients to have scheduled times to remove fluid from their abdomen, thus cutting down on emergency department procedures and unnecessary admissions. Additionally, the benefits of early paracentesis procedural performance by residents and internal medicine physicians have been demonstrated in the literature. A study by Gaetano and colleagues noted that patients undergoing early paracentesis had reduced mortality of 5.5% vs 7.5% in those undergoing late paracentesis.8 This study also showed the in-hospital mortality rate was decreased with paracentesis (6.3%) vs without paracentesis (8.9%).8 By offering residents a chance to participate in the clinic, we have shown that regular opportunities to perform paracentesis may increase the number of physicians capable of independently practicing, improve procedural competency, and improve patient access to this procedure.
Limitations
Our study was not free of bias and has potential weaknesses. The survey was sent to all current residents who have participated in the paracentesis clinic, but not every resident filled out the survey (55% of all residents across 3 years completed the survey, 68.7% who had done clinic that year completed the survey). There is a possibility that those not signed off avoided doing the survey, but we are unable to confirm this. The survey also depended on resident recall of the number of paracenteses completed or looking at their procedure log. It is possible that some procedures were not documented, changing the true number. Additionally, rating comfortability with procedures is subjective, which may also create a source of potential weakness. Future projects should include a baseline survey for residents, followed by a repeat survey a year later to show changes from baseline competency.
Conclusions
A dedicated paracentesis clinic with internal medicine resident involvement may increase resident paracentesis procedural independence, the number of procedures available and performed, and procedural comfort level.
1. Aponte EM, O’Rourke MC, Katta S. Paracentesis. StatPearls [internet]. September 5, 2022. Accessed December 11, 2023. https://www.ncbi.nlm.nih.gov/books/NBK435998
2. Barsuk JH, Feinglass J, Kozmic SE, Hohmann SF, Ganger D, Wayne DB. Specialties performing paracentesis procedures at university hospitals: implications for training and certification. J Hosp Med. 2014;9(3):162-168. doi:10.1002/jhm.2153
3. Cheng Y-W, Sandrasegaran K, Cheng K, et al. A dedicated paracentesis clinic decreases healthcare utilization for serial paracenteses in decompensated cirrhosis. Abdominal Radiology. 2017;43(8):2190-2197. doi:10.1007/s00261-017-1406-y
4. Wang J, Khan S, Wyer P, et al. The role of ultrasound-guided therapeutic paracentesis in an outpatient transitional care program: A case series. Am J Hospice Palliat Med. 2018;35(9):1256-1260. doi:10.1177/1049909118755378
5. Sall D, Warm EJ, Kinnear B, Kelleher M, Jandarov R, O’Toole J. See one, do one, forget one: early skill decay after paracentesis training. J Gen Int Med. 2020;36(5):1346-1351. doi:10.1007/s11606-020-06242-x
6. Berger M, Divilov V, Paredes H, Kesar V, Sun E. Improving resident paracentesis certification rates by using an innovative resident driven procedure service. Am J Gastroenterol. 2018;113(suppl). doi:10.14309/00000434-201810001-00980
7. Pham C, Xu A, Suaez MG. S1250 a pilot study to improve resident paracentesis training and reduce paracentesis delay in admitted patients with cirrhosis. Am J Gastroenterol. 2022;117(10S). doi:10.14309/01.ajg.0000861640.53682.93
8. Gaetano JN, Micic D, Aronsohn A, et al. The benefit of paracentesis on hospitalized adults with cirrhosis and ascites. J Gastroenterol Hepatol. 2016;31(5):1025-1030. doi:10.1111/jgh.13255
Competency in paracentesis is an important procedural skill for medical practitioners caring for patients with decompensated liver cirrhosis. Paracentesis is performed to drain ascitic fluid for both diagnosis and/or therapeutic purposes.1 While this procedure can be performed without the use of ultrasound, it is preferable to use ultrasound to identify an area of fluid that is away from dangerous anatomy including bowel loops, the liver, and spleen. After prepping the area, lidocaine is administered locally. A catheter is then inserted until fluid begins flowing freely. The catheter is connected to a suction canister or collection kit, and the patient is monitored until the flow ceases. Samples can be sent for analysis to determine the etiology of ascites, identify concerns for infection, and more.
Paracentesis is a very common procedure. Barsuk and colleagues noted that between 2010 and 2012, 97,577 procedures were performed across 120 academic medical centers and 290 affiliated hospitals.2 Patients undergo paracentesis in a variety of settings including the emergency department, inpatient hospitalizations, and clinics. Some patients may require only 1 paracentesis procedure while others may require it regularly.
Due to the rising need for paracentesis in the Central Texas Veterans Affairs Hospital (CTVAH) in Temple, a paracentesis clinic was started in February 2018. The goal of the paracentesis clinic was multifocal—to reduce hospital admissions, improve access to regularly scheduled procedures, decrease wait times, and increase patient satisfaction.3 Through the CTVAH affiliation with the Texas A&M internal medicine residency program, the paracentesis clinic started involving and training residents on this procedure. Up to 3 residents are on weekly rotation and can perform up to 6 paracentesis procedures in a week. The purpose of this article was to evaluate resident competency in paracentesis after completion of the paracentesis clinic.
Methods
The paracentesis clinic schedules up to 3 patients on Tuesdays and Thursdays between 8
A survey was sent via email to all categorical internal medicine residents across all 3 program years at the time of data collection. Competency for paracentesis sign-off was defined as completing and logging 5 procedures supervised by a competent physician who confirmed that all portions of the procedure were performed correctly. Residents were also asked to answer questions on a scale from 1 to 10, with 1 representing no confidence and 10 representing strong confidence to practice independently (Table).
We also evaluated the number of procedures performed by internal medicine residents 3 years before the clinic was started in 2015 up to the completion of 2022. The numbers were obtained by examining procedural log data for each year for all internal medicine residents.
Results
Thirty-three residents completed the survey: 10 first-year internal medicine residents (PGY1), 12 second-year residents (PGY2), and 11 third-year residents (PGY3). The mean participation was 4.8 paracentesis sessions per person for the duration of the study. The range of paracentesis procedures performed varied based on PGY year: PGY1s performed 1 to > 10 procedures, PGY2s performed 2 to > 10 procedures, and PGY3s performed 5 to > 10 procedures. Thirty-six percent of residents completed > 10 procedures in the paracentesis clinic; 82% of PGY3s had completed > 10 procedures by December of their third year. Twenty-six residents (79%) were credentialed to perform paracentesis procedures independently after performing > 5 procedures, and 7 residents were not yet cleared for procedural independence.
In the survey, residents rated their comfort with performing paracentesis procedures independently at a mean of 7.9. The mean comfort reported by PGY1s was 7.2, PGY2s was 7.3, and PGY3s was 9.3. Residents also rated their opinion on whether or not the paracentesis clinic adequately prepared them for paracentesis procedural independence; the mean was 8.9 across all residents.
The total number of procedures performed by residents at CTVAH also increased. Starting in 2015, 3 years before the clinic was started, 38 procedures were performed by internal medicine residents, followed by 72 procedures in 2016; 76 in 2017; 58 in 2018; 94 in 2019; 88 in 2020; 136 in 2021; and 188 in 2022.
Discussion
Paracentesis is a simple but invasive procedure to relieve ascites, often relieving patients’ symptoms, preventing hospital admission, and increasing patient satisfaction.4 The CTVAH does not have the capacity to perform outpatient paracentesis effectively in its emergency or radiology departments. Furthermore, the use of the emergency or radiology departments for routine paracentesis may not be feasible due to the acuity of care being provided, as these procedures can be time consuming and can draw away critical resources and time from patients that need emergent care. The paracentesis clinic was then formed to provide veterans access to the procedural care they need, while also preparing residents to ably and confidently perform the procedure independently.
Based on our study, most residents were cleared to independently perform paracentesis procedures across all 3 years, with 79% of residents having completed the required 5 supervised procedures to independently practice. A study assessing unsupervised practice standards showed that paracentesis skill declines as soon as 3 months after training. However, retraining was shown to potentially interrupt this skill decline.5 Studies have shown that procedure-driven electives or services significantly improved paracentesis certification rates and total logged procedures, with minimal funding or scheduling changes required.6 Our clinic showed a significant increase in the number of procedures logged starting with the minimum of 38 procedures in 2015 and ending with 188 procedures logged at the end of 2022.
By allowing residents to routinely return to the paracentesis clinic across all 3 years, residents were more likely to feel comfortable independently performing the procedure, with residents reporting a mean comfort score of 7.9. The spaced repetition and ability to work with the clinic during elective time allows regular opportunities to undergo supervised training in a controlled environment and created scheduled retraining opportunities. Future studies should evaluate residents prior to each paracentesis clinic to ascertain if skill decline is occurring at a slower rate.
The inpatient effect of the clinic is also multifocal. Pham and colleagues showed that integrating paracentesis into timely training can reduce paracentesis delay and delays in care.7 By increasing the volume of procedures each resident performs and creating a sense of confidence amongst residents, the clinic increases the number of residents able and willing to perform inpatient procedures, thus reducing the number of unnecessary consultations and hospital resources. One of the reasons the paracentesis clinic was started was to allow patients to have scheduled times to remove fluid from their abdomen, thus cutting down on emergency department procedures and unnecessary admissions. Additionally, the benefits of early paracentesis procedural performance by residents and internal medicine physicians have been demonstrated in the literature. A study by Gaetano and colleagues noted that patients undergoing early paracentesis had reduced mortality of 5.5% vs 7.5% in those undergoing late paracentesis.8 This study also showed the in-hospital mortality rate was decreased with paracentesis (6.3%) vs without paracentesis (8.9%).8 By offering residents a chance to participate in the clinic, we have shown that regular opportunities to perform paracentesis may increase the number of physicians capable of independently practicing, improve procedural competency, and improve patient access to this procedure.
Limitations
Our study was not free of bias and has potential weaknesses. The survey was sent to all current residents who have participated in the paracentesis clinic, but not every resident filled out the survey (55% of all residents across 3 years completed the survey, 68.7% who had done clinic that year completed the survey). There is a possibility that those not signed off avoided doing the survey, but we are unable to confirm this. The survey also depended on resident recall of the number of paracenteses completed or looking at their procedure log. It is possible that some procedures were not documented, changing the true number. Additionally, rating comfortability with procedures is subjective, which may also create a source of potential weakness. Future projects should include a baseline survey for residents, followed by a repeat survey a year later to show changes from baseline competency.
Conclusions
A dedicated paracentesis clinic with internal medicine resident involvement may increase resident paracentesis procedural independence, the number of procedures available and performed, and procedural comfort level.
Competency in paracentesis is an important procedural skill for medical practitioners caring for patients with decompensated liver cirrhosis. Paracentesis is performed to drain ascitic fluid for both diagnosis and/or therapeutic purposes.1 While this procedure can be performed without the use of ultrasound, it is preferable to use ultrasound to identify an area of fluid that is away from dangerous anatomy including bowel loops, the liver, and spleen. After prepping the area, lidocaine is administered locally. A catheter is then inserted until fluid begins flowing freely. The catheter is connected to a suction canister or collection kit, and the patient is monitored until the flow ceases. Samples can be sent for analysis to determine the etiology of ascites, identify concerns for infection, and more.
Paracentesis is a very common procedure. Barsuk and colleagues noted that between 2010 and 2012, 97,577 procedures were performed across 120 academic medical centers and 290 affiliated hospitals.2 Patients undergo paracentesis in a variety of settings including the emergency department, inpatient hospitalizations, and clinics. Some patients may require only 1 paracentesis procedure while others may require it regularly.
Due to the rising need for paracentesis in the Central Texas Veterans Affairs Hospital (CTVAH) in Temple, a paracentesis clinic was started in February 2018. The goal of the paracentesis clinic was multifocal—to reduce hospital admissions, improve access to regularly scheduled procedures, decrease wait times, and increase patient satisfaction.3 Through the CTVAH affiliation with the Texas A&M internal medicine residency program, the paracentesis clinic started involving and training residents on this procedure. Up to 3 residents are on weekly rotation and can perform up to 6 paracentesis procedures in a week. The purpose of this article was to evaluate resident competency in paracentesis after completion of the paracentesis clinic.
Methods
The paracentesis clinic schedules up to 3 patients on Tuesdays and Thursdays between 8
A survey was sent via email to all categorical internal medicine residents across all 3 program years at the time of data collection. Competency for paracentesis sign-off was defined as completing and logging 5 procedures supervised by a competent physician who confirmed that all portions of the procedure were performed correctly. Residents were also asked to answer questions on a scale from 1 to 10, with 1 representing no confidence and 10 representing strong confidence to practice independently (Table).
We also evaluated the number of procedures performed by internal medicine residents 3 years before the clinic was started in 2015 up to the completion of 2022. The numbers were obtained by examining procedural log data for each year for all internal medicine residents.
Results
Thirty-three residents completed the survey: 10 first-year internal medicine residents (PGY1), 12 second-year residents (PGY2), and 11 third-year residents (PGY3). The mean participation was 4.8 paracentesis sessions per person for the duration of the study. The range of paracentesis procedures performed varied based on PGY year: PGY1s performed 1 to > 10 procedures, PGY2s performed 2 to > 10 procedures, and PGY3s performed 5 to > 10 procedures. Thirty-six percent of residents completed > 10 procedures in the paracentesis clinic; 82% of PGY3s had completed > 10 procedures by December of their third year. Twenty-six residents (79%) were credentialed to perform paracentesis procedures independently after performing > 5 procedures, and 7 residents were not yet cleared for procedural independence.
In the survey, residents rated their comfort with performing paracentesis procedures independently at a mean of 7.9. The mean comfort reported by PGY1s was 7.2, PGY2s was 7.3, and PGY3s was 9.3. Residents also rated their opinion on whether or not the paracentesis clinic adequately prepared them for paracentesis procedural independence; the mean was 8.9 across all residents.
The total number of procedures performed by residents at CTVAH also increased. Starting in 2015, 3 years before the clinic was started, 38 procedures were performed by internal medicine residents, followed by 72 procedures in 2016; 76 in 2017; 58 in 2018; 94 in 2019; 88 in 2020; 136 in 2021; and 188 in 2022.
Discussion
Paracentesis is a simple but invasive procedure to relieve ascites, often relieving patients’ symptoms, preventing hospital admission, and increasing patient satisfaction.4 The CTVAH does not have the capacity to perform outpatient paracentesis effectively in its emergency or radiology departments. Furthermore, the use of the emergency or radiology departments for routine paracentesis may not be feasible due to the acuity of care being provided, as these procedures can be time consuming and can draw away critical resources and time from patients that need emergent care. The paracentesis clinic was then formed to provide veterans access to the procedural care they need, while also preparing residents to ably and confidently perform the procedure independently.
Based on our study, most residents were cleared to independently perform paracentesis procedures across all 3 years, with 79% of residents having completed the required 5 supervised procedures to independently practice. A study assessing unsupervised practice standards showed that paracentesis skill declines as soon as 3 months after training. However, retraining was shown to potentially interrupt this skill decline.5 Studies have shown that procedure-driven electives or services significantly improved paracentesis certification rates and total logged procedures, with minimal funding or scheduling changes required.6 Our clinic showed a significant increase in the number of procedures logged starting with the minimum of 38 procedures in 2015 and ending with 188 procedures logged at the end of 2022.
By allowing residents to routinely return to the paracentesis clinic across all 3 years, residents were more likely to feel comfortable independently performing the procedure, with residents reporting a mean comfort score of 7.9. The spaced repetition and ability to work with the clinic during elective time allows regular opportunities to undergo supervised training in a controlled environment and created scheduled retraining opportunities. Future studies should evaluate residents prior to each paracentesis clinic to ascertain if skill decline is occurring at a slower rate.
The inpatient effect of the clinic is also multifocal. Pham and colleagues showed that integrating paracentesis into timely training can reduce paracentesis delay and delays in care.7 By increasing the volume of procedures each resident performs and creating a sense of confidence amongst residents, the clinic increases the number of residents able and willing to perform inpatient procedures, thus reducing the number of unnecessary consultations and hospital resources. One of the reasons the paracentesis clinic was started was to allow patients to have scheduled times to remove fluid from their abdomen, thus cutting down on emergency department procedures and unnecessary admissions. Additionally, the benefits of early paracentesis procedural performance by residents and internal medicine physicians have been demonstrated in the literature. A study by Gaetano and colleagues noted that patients undergoing early paracentesis had reduced mortality of 5.5% vs 7.5% in those undergoing late paracentesis.8 This study also showed the in-hospital mortality rate was decreased with paracentesis (6.3%) vs without paracentesis (8.9%).8 By offering residents a chance to participate in the clinic, we have shown that regular opportunities to perform paracentesis may increase the number of physicians capable of independently practicing, improve procedural competency, and improve patient access to this procedure.
Limitations
Our study was not free of bias and has potential weaknesses. The survey was sent to all current residents who have participated in the paracentesis clinic, but not every resident filled out the survey (55% of all residents across 3 years completed the survey, 68.7% who had done clinic that year completed the survey). There is a possibility that those not signed off avoided doing the survey, but we are unable to confirm this. The survey also depended on resident recall of the number of paracenteses completed or looking at their procedure log. It is possible that some procedures were not documented, changing the true number. Additionally, rating comfortability with procedures is subjective, which may also create a source of potential weakness. Future projects should include a baseline survey for residents, followed by a repeat survey a year later to show changes from baseline competency.
Conclusions
A dedicated paracentesis clinic with internal medicine resident involvement may increase resident paracentesis procedural independence, the number of procedures available and performed, and procedural comfort level.
1. Aponte EM, O’Rourke MC, Katta S. Paracentesis. StatPearls [internet]. September 5, 2022. Accessed December 11, 2023. https://www.ncbi.nlm.nih.gov/books/NBK435998
2. Barsuk JH, Feinglass J, Kozmic SE, Hohmann SF, Ganger D, Wayne DB. Specialties performing paracentesis procedures at university hospitals: implications for training and certification. J Hosp Med. 2014;9(3):162-168. doi:10.1002/jhm.2153
3. Cheng Y-W, Sandrasegaran K, Cheng K, et al. A dedicated paracentesis clinic decreases healthcare utilization for serial paracenteses in decompensated cirrhosis. Abdominal Radiology. 2017;43(8):2190-2197. doi:10.1007/s00261-017-1406-y
4. Wang J, Khan S, Wyer P, et al. The role of ultrasound-guided therapeutic paracentesis in an outpatient transitional care program: A case series. Am J Hospice Palliat Med. 2018;35(9):1256-1260. doi:10.1177/1049909118755378
5. Sall D, Warm EJ, Kinnear B, Kelleher M, Jandarov R, O’Toole J. See one, do one, forget one: early skill decay after paracentesis training. J Gen Int Med. 2020;36(5):1346-1351. doi:10.1007/s11606-020-06242-x
6. Berger M, Divilov V, Paredes H, Kesar V, Sun E. Improving resident paracentesis certification rates by using an innovative resident driven procedure service. Am J Gastroenterol. 2018;113(suppl). doi:10.14309/00000434-201810001-00980
7. Pham C, Xu A, Suaez MG. S1250 a pilot study to improve resident paracentesis training and reduce paracentesis delay in admitted patients with cirrhosis. Am J Gastroenterol. 2022;117(10S). doi:10.14309/01.ajg.0000861640.53682.93
8. Gaetano JN, Micic D, Aronsohn A, et al. The benefit of paracentesis on hospitalized adults with cirrhosis and ascites. J Gastroenterol Hepatol. 2016;31(5):1025-1030. doi:10.1111/jgh.13255
1. Aponte EM, O’Rourke MC, Katta S. Paracentesis. StatPearls [internet]. September 5, 2022. Accessed December 11, 2023. https://www.ncbi.nlm.nih.gov/books/NBK435998
2. Barsuk JH, Feinglass J, Kozmic SE, Hohmann SF, Ganger D, Wayne DB. Specialties performing paracentesis procedures at university hospitals: implications for training and certification. J Hosp Med. 2014;9(3):162-168. doi:10.1002/jhm.2153
3. Cheng Y-W, Sandrasegaran K, Cheng K, et al. A dedicated paracentesis clinic decreases healthcare utilization for serial paracenteses in decompensated cirrhosis. Abdominal Radiology. 2017;43(8):2190-2197. doi:10.1007/s00261-017-1406-y
4. Wang J, Khan S, Wyer P, et al. The role of ultrasound-guided therapeutic paracentesis in an outpatient transitional care program: A case series. Am J Hospice Palliat Med. 2018;35(9):1256-1260. doi:10.1177/1049909118755378
5. Sall D, Warm EJ, Kinnear B, Kelleher M, Jandarov R, O’Toole J. See one, do one, forget one: early skill decay after paracentesis training. J Gen Int Med. 2020;36(5):1346-1351. doi:10.1007/s11606-020-06242-x
6. Berger M, Divilov V, Paredes H, Kesar V, Sun E. Improving resident paracentesis certification rates by using an innovative resident driven procedure service. Am J Gastroenterol. 2018;113(suppl). doi:10.14309/00000434-201810001-00980
7. Pham C, Xu A, Suaez MG. S1250 a pilot study to improve resident paracentesis training and reduce paracentesis delay in admitted patients with cirrhosis. Am J Gastroenterol. 2022;117(10S). doi:10.14309/01.ajg.0000861640.53682.93
8. Gaetano JN, Micic D, Aronsohn A, et al. The benefit of paracentesis on hospitalized adults with cirrhosis and ascites. J Gastroenterol Hepatol. 2016;31(5):1025-1030. doi:10.1111/jgh.13255
Piperacillin/Tazobactam Use vs Cefepime May Be Associated With Acute Decompensated Heart Failure
Piperacillin/tazobactam (PTZ) is a combination IV antibiotic comprised of the semisynthetic antipseudomonal β-lactam, piperacillin sodium, and the β-lactamase inhibitor, tazobactam sodium.1 PTZ is extensively prescribed in the hospital setting for a multitude of infections including but not limited to the US Food and Drug Administration–approved indications: intra-abdominal infection, skin and skin structure infection (SSTI), urinary tract infection (UTI), and pneumonia. Given its broad spectrum of activity and relative safety profile, PTZ is a mainstay of many empiric IV antibiotic regimens. The primary elimination pathway for PTZ is renal excretion, and dosage adjustments are recommended with reduced creatinine clearance. Additionally, PTZ use has been associated with acute renal injury and delayed renal recovery.1-3
There are various mechanisms through which medications can contribute to acute decomopensated heart failure (ADHF).4 These mechanisms include direct cardiotoxicity; negative inotropic, lusitropic, or chronotropic effects; exacerbating hypertension; sodium loading; and drug-drug interactions that limit the benefits of heart failure (HF) medications. One potentially overlooked constituent of PTZ is the sodium content, with the standard formulation containing 65 mg of sodium per gram of piperacillin.1-3 Furthermore, PTZ must be diluted in 50 to 150 mL of diluent, commonly 0.9% sodium chloride, which can contribute an additional 177 to 531 mg of sodium per dose. PTZ prescribing information advises caution for use in patients with decreased renal, hepatic, and/or cardiac function and notes that geriatric patients, particularly with HF, may be at risk of impaired natriuresis in the setting of large sodium doses.
It is estimated that roughly 6.2 million adults in the United States have HF and prevalence continues to rise.5,6 Mortality rates after hospitalization due to HF are 20% to 25% at 1 year. Health care expenditures for the management of HF surpass $30 billion per year in the US, with most of this cost attributed to hospitalizations. Consequently, it is important to continue to identify and practice preventative strategies when managing patients with HF.
Methods
This single-center, retrospective, cohort study was conducted at James H. Quillen Veterans Affairs Medical Center (JHQVAMC) in Mountain Home, Tennessee, a 174-bed tertiary medical center. The purpose of this study was to compare the incidence of ADHF in patients who received PTZ vs cefepime (CFP). This project was reviewed by the JHQVAMC Institutional Review Board and deemed exempt as a clinical process improvement operations activity.
The antimicrobial stewardship team at JHQVAMC reviewed the use of PTZ in veterans between January 1, 2018, to December 31, 2019, and compared baseline demographics, history of HF, and outcomes in patients receiving analogous broad-spectrum empiric antibiotic therapy with CFP.
Statistical Analysis
Analysis was conducted with R Software. Pearson χ2 and t tests were used to compare baseline demographics, length of stay, readmission, and mortality. Significance used was α = .05.
Results
A retrospective chart review was performed on 389 veterans. Of the 389, 204 patients received at least 24 hours of PTZ, and 185 patients received CFP. The mean age in both groups was 75 years. Patients in the PTZ group were more likely to have been admitted with the diagnosis of pneumonia (105 vs 49, P < .001). However, 29 patients (15.7%) in the CFP group were admitted with a UTI diagnosis compared with 6 patients (2.9%) in the PTZ group (P < .001) and 62 patients (33.5%) in the CFP group were admitted with a SSTI diagnosis compared with 48 patients (23.5%) in the PTZ group (P = .03). Otherwise, there were no differences between other admitting diagnoses. Additionally, there was no difference in prior history of HF between groups (Table 1).
Twenty-five patients (12.3%) in the PTZ group and 4 patients (2.2%) in the CFP group were subsequently diagnosed with ADHF (P < .001). Hospital readmissions due to HF were higher in the PTZ group compared with the CFP group (11 vs 2, P = .02). Hospital readmission due to other causes was not significantly different between groups. Hospital readmission due to infection occurred in 18 patients who received PTZ and 25 who received CFP (8.8% vs 13.5%, P = .14). Hospital readmission due to any other indication occurred in 24 patients who received PTZ and 24 who received CFP (11.8% vs 13.0%, P = .72). There was no statistically significant difference in all-cause mortality during the associated admission or within 6 months of discharge between groups, with 59 total deaths in the PTZ group and 50 in the CFP group (28.9% vs 27.0%, P = .63).
There was no difference in length of stay outcomes between patients receiving PTZ compared with CFP. Twenty-eight patients in the PTZ group and 20 in the CFP group had a length of stay duration of < 3 days (13.7% vs 10.8%, P = .46). Seventy-three patients in the PTZ group and 76 in the CFP group had a length of stay duration of 4 to 6 days (36.3% vs 41.1%, P = .28). One hundred three patients in the PTZ group and 89 in the CFP group had a length of stay duration ≥ 7 days (50.5% vs 48.1%, P = .78). Table 2 includes a complete overview of primary and secondary endpoint results.
Discussion
The American Heart Association (AHA) lists PTZ as a medication that may cause or exacerbate HF, though no studies have identified a clear association between PTZ use and ADHF.4 Sodium restriction is consistently recommended as an important strategy for the prevention of ADHF. Accordingly, PTZ prescribing information and the AHA advise careful consideration with PTZ use in this patient population.1,4
The specific mechanism responsible for the association of PTZ with cardiac-related adverse outcomes is unclear. It is easy to presume that the sodium content of PTZ is solely responsible; however, other antibiotic regimens not included as agents of concern by the AHA, such as meropenem, can approach similar overall daily sodium amounts.4,7 Additionally, total sodium and volume can also be contributed by various IV medications and fluids. This study did not evaluate total sodium intake from all sources, but it is notable that this study identified a possible trend toward the risk of ADHF with PTZ use in a routine practice environment. It is reasonable to postulate additional intrinsic properties of PTZ may be contributing to the development of ADHF, such as its association with renal injury possibly resulting in increased fluid retainment and subsequent fluid volume overload.1,2,4 Other hypothesized mechanisms may include those previously described, such as direct myocardial toxicity; negative inotropic, lusitropic, or chronotropic effects; exacerbating hypertension; and drug-drug interactions that limit the benefits of HF medications, although these have not been overtly associated with PTZ in the literature to date.4,8
ADHF can present similarly to other acute pulmonary conditions, including pneumonia.9,10 It is important to acknowledge the challenge this creates for diagnosticians to differentiate between these conditions rapidly and precisely. As a result, this patient population is likely at increased risk of IV antibiotic exposure. Other studies have identified worse outcomes in patients who receive potentially unwarranted IV antibiotics in patients with ADHF.9,10 The results of this study further emphasize the importance of careful considerate antibiotic selection and overall avoidance of unnecessary antibiotic exposure to limit potential adverse outcomes.
Limitations
There are various limitations to this study. Firstly, no women were included due to the predominantly male population within the Veterans Health Administration system. Secondly, this study was retrospective in design and was therefore limited to the completeness and accuracy of the available data collected. Additionally, this study evaluated any ADHF episode during the associated hospitalization as the primary endpoint. The time to diagnosis of ADHF in relation to PTZ initiation was not evaluated, which may have helped better elucidate this possible association. Furthermore, while a significant statistical difference was identified, the smaller sample size may have limited the ability to accurately identify differences in lower event rate outcomes.
Conclusions
This study identifies an association between PTZ use and significant cardiac-related adverse outcomes, including increased incidence of ADHF and readmission due to HF exacerbation. While more research is needed to define the exact mechanisms by which PTZ may precipitate acute decompensation in patients with HF, it is judicious to consider close monitoring or the avoidance of PTZ when appropriate antibiotic alternatives are available in patients with a known history of HF.
1. Zosyn. Package insert. Wyeth Pharmaceuticals; 2020.
2. Jensen JU, Hein L, Lundgren B, et al. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial. BMJ Open. 2012;2(2):e000635. Published 2012 Mar 11. doi:10.1136/bmjopen-2011-000635
3. Kadomura S, Takekuma Y, Sato Y, et al. Higher incidence of acute kidney injury in patients treated with piperacillin/tazobactam than in patients treated with cefepime: a single-center retrospective cohort study. J Pharm Health Care Sci. 2019;5:13. Published 2019 Jun 12. doi:10.1186/s40780-019-0142-6
4. Page RL 2nd, O’Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016;134(6):e32-e69. doi:10.1161/CIR.0000000000000426
5. Bozkurt B, Hershberger RE, Butler J, et al. 2021 ACC/AHA key data elements and definitions for heart failure: a report of the American College of Cardiology/American Heart Association task force on clinical data standards. J Am Coll Cardiol. 2021;77(16):2053-2150.
6. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 2021;143(8):e254-e743. doi:10.1161/CIR.0000000000000950
7. Merrem. Package insert. Pfizer Labs; 2021.
8. Keller GA, Alvarez PA, Ponte ML, et al. Drug-induced QTc interval prolongation: a multicenter study to detect drugs and clinical factors involved in every day practice. Curr Drug Saf. 2016;11(1):86-98. doi:10.2174/1574886311207040262
9. Wu S, Alikhil M, Forsyth R, Allen B. Impact of potentially unwarranted intravenous antibiotics targeting pulmonary infections in acute decompensated heart failure. J Pharm Technol. 2021;37(6):298-303. doi:10.1177/87551225211038020
10. Frisbee J, Heidel RH, Rasnake MS. Adverse outcomes associated with potentially inappropriate antibiotic use in heart failure admissions. Open Forum Infect Dis. 2019;6(6):ofz220. doi:10.1093/ofid/ofz220
Piperacillin/tazobactam (PTZ) is a combination IV antibiotic comprised of the semisynthetic antipseudomonal β-lactam, piperacillin sodium, and the β-lactamase inhibitor, tazobactam sodium.1 PTZ is extensively prescribed in the hospital setting for a multitude of infections including but not limited to the US Food and Drug Administration–approved indications: intra-abdominal infection, skin and skin structure infection (SSTI), urinary tract infection (UTI), and pneumonia. Given its broad spectrum of activity and relative safety profile, PTZ is a mainstay of many empiric IV antibiotic regimens. The primary elimination pathway for PTZ is renal excretion, and dosage adjustments are recommended with reduced creatinine clearance. Additionally, PTZ use has been associated with acute renal injury and delayed renal recovery.1-3
There are various mechanisms through which medications can contribute to acute decomopensated heart failure (ADHF).4 These mechanisms include direct cardiotoxicity; negative inotropic, lusitropic, or chronotropic effects; exacerbating hypertension; sodium loading; and drug-drug interactions that limit the benefits of heart failure (HF) medications. One potentially overlooked constituent of PTZ is the sodium content, with the standard formulation containing 65 mg of sodium per gram of piperacillin.1-3 Furthermore, PTZ must be diluted in 50 to 150 mL of diluent, commonly 0.9% sodium chloride, which can contribute an additional 177 to 531 mg of sodium per dose. PTZ prescribing information advises caution for use in patients with decreased renal, hepatic, and/or cardiac function and notes that geriatric patients, particularly with HF, may be at risk of impaired natriuresis in the setting of large sodium doses.
It is estimated that roughly 6.2 million adults in the United States have HF and prevalence continues to rise.5,6 Mortality rates after hospitalization due to HF are 20% to 25% at 1 year. Health care expenditures for the management of HF surpass $30 billion per year in the US, with most of this cost attributed to hospitalizations. Consequently, it is important to continue to identify and practice preventative strategies when managing patients with HF.
Methods
This single-center, retrospective, cohort study was conducted at James H. Quillen Veterans Affairs Medical Center (JHQVAMC) in Mountain Home, Tennessee, a 174-bed tertiary medical center. The purpose of this study was to compare the incidence of ADHF in patients who received PTZ vs cefepime (CFP). This project was reviewed by the JHQVAMC Institutional Review Board and deemed exempt as a clinical process improvement operations activity.
The antimicrobial stewardship team at JHQVAMC reviewed the use of PTZ in veterans between January 1, 2018, to December 31, 2019, and compared baseline demographics, history of HF, and outcomes in patients receiving analogous broad-spectrum empiric antibiotic therapy with CFP.
Statistical Analysis
Analysis was conducted with R Software. Pearson χ2 and t tests were used to compare baseline demographics, length of stay, readmission, and mortality. Significance used was α = .05.
Results
A retrospective chart review was performed on 389 veterans. Of the 389, 204 patients received at least 24 hours of PTZ, and 185 patients received CFP. The mean age in both groups was 75 years. Patients in the PTZ group were more likely to have been admitted with the diagnosis of pneumonia (105 vs 49, P < .001). However, 29 patients (15.7%) in the CFP group were admitted with a UTI diagnosis compared with 6 patients (2.9%) in the PTZ group (P < .001) and 62 patients (33.5%) in the CFP group were admitted with a SSTI diagnosis compared with 48 patients (23.5%) in the PTZ group (P = .03). Otherwise, there were no differences between other admitting diagnoses. Additionally, there was no difference in prior history of HF between groups (Table 1).
Twenty-five patients (12.3%) in the PTZ group and 4 patients (2.2%) in the CFP group were subsequently diagnosed with ADHF (P < .001). Hospital readmissions due to HF were higher in the PTZ group compared with the CFP group (11 vs 2, P = .02). Hospital readmission due to other causes was not significantly different between groups. Hospital readmission due to infection occurred in 18 patients who received PTZ and 25 who received CFP (8.8% vs 13.5%, P = .14). Hospital readmission due to any other indication occurred in 24 patients who received PTZ and 24 who received CFP (11.8% vs 13.0%, P = .72). There was no statistically significant difference in all-cause mortality during the associated admission or within 6 months of discharge between groups, with 59 total deaths in the PTZ group and 50 in the CFP group (28.9% vs 27.0%, P = .63).
There was no difference in length of stay outcomes between patients receiving PTZ compared with CFP. Twenty-eight patients in the PTZ group and 20 in the CFP group had a length of stay duration of < 3 days (13.7% vs 10.8%, P = .46). Seventy-three patients in the PTZ group and 76 in the CFP group had a length of stay duration of 4 to 6 days (36.3% vs 41.1%, P = .28). One hundred three patients in the PTZ group and 89 in the CFP group had a length of stay duration ≥ 7 days (50.5% vs 48.1%, P = .78). Table 2 includes a complete overview of primary and secondary endpoint results.
Discussion
The American Heart Association (AHA) lists PTZ as a medication that may cause or exacerbate HF, though no studies have identified a clear association between PTZ use and ADHF.4 Sodium restriction is consistently recommended as an important strategy for the prevention of ADHF. Accordingly, PTZ prescribing information and the AHA advise careful consideration with PTZ use in this patient population.1,4
The specific mechanism responsible for the association of PTZ with cardiac-related adverse outcomes is unclear. It is easy to presume that the sodium content of PTZ is solely responsible; however, other antibiotic regimens not included as agents of concern by the AHA, such as meropenem, can approach similar overall daily sodium amounts.4,7 Additionally, total sodium and volume can also be contributed by various IV medications and fluids. This study did not evaluate total sodium intake from all sources, but it is notable that this study identified a possible trend toward the risk of ADHF with PTZ use in a routine practice environment. It is reasonable to postulate additional intrinsic properties of PTZ may be contributing to the development of ADHF, such as its association with renal injury possibly resulting in increased fluid retainment and subsequent fluid volume overload.1,2,4 Other hypothesized mechanisms may include those previously described, such as direct myocardial toxicity; negative inotropic, lusitropic, or chronotropic effects; exacerbating hypertension; and drug-drug interactions that limit the benefits of HF medications, although these have not been overtly associated with PTZ in the literature to date.4,8
ADHF can present similarly to other acute pulmonary conditions, including pneumonia.9,10 It is important to acknowledge the challenge this creates for diagnosticians to differentiate between these conditions rapidly and precisely. As a result, this patient population is likely at increased risk of IV antibiotic exposure. Other studies have identified worse outcomes in patients who receive potentially unwarranted IV antibiotics in patients with ADHF.9,10 The results of this study further emphasize the importance of careful considerate antibiotic selection and overall avoidance of unnecessary antibiotic exposure to limit potential adverse outcomes.
Limitations
There are various limitations to this study. Firstly, no women were included due to the predominantly male population within the Veterans Health Administration system. Secondly, this study was retrospective in design and was therefore limited to the completeness and accuracy of the available data collected. Additionally, this study evaluated any ADHF episode during the associated hospitalization as the primary endpoint. The time to diagnosis of ADHF in relation to PTZ initiation was not evaluated, which may have helped better elucidate this possible association. Furthermore, while a significant statistical difference was identified, the smaller sample size may have limited the ability to accurately identify differences in lower event rate outcomes.
Conclusions
This study identifies an association between PTZ use and significant cardiac-related adverse outcomes, including increased incidence of ADHF and readmission due to HF exacerbation. While more research is needed to define the exact mechanisms by which PTZ may precipitate acute decompensation in patients with HF, it is judicious to consider close monitoring or the avoidance of PTZ when appropriate antibiotic alternatives are available in patients with a known history of HF.
Piperacillin/tazobactam (PTZ) is a combination IV antibiotic comprised of the semisynthetic antipseudomonal β-lactam, piperacillin sodium, and the β-lactamase inhibitor, tazobactam sodium.1 PTZ is extensively prescribed in the hospital setting for a multitude of infections including but not limited to the US Food and Drug Administration–approved indications: intra-abdominal infection, skin and skin structure infection (SSTI), urinary tract infection (UTI), and pneumonia. Given its broad spectrum of activity and relative safety profile, PTZ is a mainstay of many empiric IV antibiotic regimens. The primary elimination pathway for PTZ is renal excretion, and dosage adjustments are recommended with reduced creatinine clearance. Additionally, PTZ use has been associated with acute renal injury and delayed renal recovery.1-3
There are various mechanisms through which medications can contribute to acute decomopensated heart failure (ADHF).4 These mechanisms include direct cardiotoxicity; negative inotropic, lusitropic, or chronotropic effects; exacerbating hypertension; sodium loading; and drug-drug interactions that limit the benefits of heart failure (HF) medications. One potentially overlooked constituent of PTZ is the sodium content, with the standard formulation containing 65 mg of sodium per gram of piperacillin.1-3 Furthermore, PTZ must be diluted in 50 to 150 mL of diluent, commonly 0.9% sodium chloride, which can contribute an additional 177 to 531 mg of sodium per dose. PTZ prescribing information advises caution for use in patients with decreased renal, hepatic, and/or cardiac function and notes that geriatric patients, particularly with HF, may be at risk of impaired natriuresis in the setting of large sodium doses.
It is estimated that roughly 6.2 million adults in the United States have HF and prevalence continues to rise.5,6 Mortality rates after hospitalization due to HF are 20% to 25% at 1 year. Health care expenditures for the management of HF surpass $30 billion per year in the US, with most of this cost attributed to hospitalizations. Consequently, it is important to continue to identify and practice preventative strategies when managing patients with HF.
Methods
This single-center, retrospective, cohort study was conducted at James H. Quillen Veterans Affairs Medical Center (JHQVAMC) in Mountain Home, Tennessee, a 174-bed tertiary medical center. The purpose of this study was to compare the incidence of ADHF in patients who received PTZ vs cefepime (CFP). This project was reviewed by the JHQVAMC Institutional Review Board and deemed exempt as a clinical process improvement operations activity.
The antimicrobial stewardship team at JHQVAMC reviewed the use of PTZ in veterans between January 1, 2018, to December 31, 2019, and compared baseline demographics, history of HF, and outcomes in patients receiving analogous broad-spectrum empiric antibiotic therapy with CFP.
Statistical Analysis
Analysis was conducted with R Software. Pearson χ2 and t tests were used to compare baseline demographics, length of stay, readmission, and mortality. Significance used was α = .05.
Results
A retrospective chart review was performed on 389 veterans. Of the 389, 204 patients received at least 24 hours of PTZ, and 185 patients received CFP. The mean age in both groups was 75 years. Patients in the PTZ group were more likely to have been admitted with the diagnosis of pneumonia (105 vs 49, P < .001). However, 29 patients (15.7%) in the CFP group were admitted with a UTI diagnosis compared with 6 patients (2.9%) in the PTZ group (P < .001) and 62 patients (33.5%) in the CFP group were admitted with a SSTI diagnosis compared with 48 patients (23.5%) in the PTZ group (P = .03). Otherwise, there were no differences between other admitting diagnoses. Additionally, there was no difference in prior history of HF between groups (Table 1).
Twenty-five patients (12.3%) in the PTZ group and 4 patients (2.2%) in the CFP group were subsequently diagnosed with ADHF (P < .001). Hospital readmissions due to HF were higher in the PTZ group compared with the CFP group (11 vs 2, P = .02). Hospital readmission due to other causes was not significantly different between groups. Hospital readmission due to infection occurred in 18 patients who received PTZ and 25 who received CFP (8.8% vs 13.5%, P = .14). Hospital readmission due to any other indication occurred in 24 patients who received PTZ and 24 who received CFP (11.8% vs 13.0%, P = .72). There was no statistically significant difference in all-cause mortality during the associated admission or within 6 months of discharge between groups, with 59 total deaths in the PTZ group and 50 in the CFP group (28.9% vs 27.0%, P = .63).
There was no difference in length of stay outcomes between patients receiving PTZ compared with CFP. Twenty-eight patients in the PTZ group and 20 in the CFP group had a length of stay duration of < 3 days (13.7% vs 10.8%, P = .46). Seventy-three patients in the PTZ group and 76 in the CFP group had a length of stay duration of 4 to 6 days (36.3% vs 41.1%, P = .28). One hundred three patients in the PTZ group and 89 in the CFP group had a length of stay duration ≥ 7 days (50.5% vs 48.1%, P = .78). Table 2 includes a complete overview of primary and secondary endpoint results.
Discussion
The American Heart Association (AHA) lists PTZ as a medication that may cause or exacerbate HF, though no studies have identified a clear association between PTZ use and ADHF.4 Sodium restriction is consistently recommended as an important strategy for the prevention of ADHF. Accordingly, PTZ prescribing information and the AHA advise careful consideration with PTZ use in this patient population.1,4
The specific mechanism responsible for the association of PTZ with cardiac-related adverse outcomes is unclear. It is easy to presume that the sodium content of PTZ is solely responsible; however, other antibiotic regimens not included as agents of concern by the AHA, such as meropenem, can approach similar overall daily sodium amounts.4,7 Additionally, total sodium and volume can also be contributed by various IV medications and fluids. This study did not evaluate total sodium intake from all sources, but it is notable that this study identified a possible trend toward the risk of ADHF with PTZ use in a routine practice environment. It is reasonable to postulate additional intrinsic properties of PTZ may be contributing to the development of ADHF, such as its association with renal injury possibly resulting in increased fluid retainment and subsequent fluid volume overload.1,2,4 Other hypothesized mechanisms may include those previously described, such as direct myocardial toxicity; negative inotropic, lusitropic, or chronotropic effects; exacerbating hypertension; and drug-drug interactions that limit the benefits of HF medications, although these have not been overtly associated with PTZ in the literature to date.4,8
ADHF can present similarly to other acute pulmonary conditions, including pneumonia.9,10 It is important to acknowledge the challenge this creates for diagnosticians to differentiate between these conditions rapidly and precisely. As a result, this patient population is likely at increased risk of IV antibiotic exposure. Other studies have identified worse outcomes in patients who receive potentially unwarranted IV antibiotics in patients with ADHF.9,10 The results of this study further emphasize the importance of careful considerate antibiotic selection and overall avoidance of unnecessary antibiotic exposure to limit potential adverse outcomes.
Limitations
There are various limitations to this study. Firstly, no women were included due to the predominantly male population within the Veterans Health Administration system. Secondly, this study was retrospective in design and was therefore limited to the completeness and accuracy of the available data collected. Additionally, this study evaluated any ADHF episode during the associated hospitalization as the primary endpoint. The time to diagnosis of ADHF in relation to PTZ initiation was not evaluated, which may have helped better elucidate this possible association. Furthermore, while a significant statistical difference was identified, the smaller sample size may have limited the ability to accurately identify differences in lower event rate outcomes.
Conclusions
This study identifies an association between PTZ use and significant cardiac-related adverse outcomes, including increased incidence of ADHF and readmission due to HF exacerbation. While more research is needed to define the exact mechanisms by which PTZ may precipitate acute decompensation in patients with HF, it is judicious to consider close monitoring or the avoidance of PTZ when appropriate antibiotic alternatives are available in patients with a known history of HF.
1. Zosyn. Package insert. Wyeth Pharmaceuticals; 2020.
2. Jensen JU, Hein L, Lundgren B, et al. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial. BMJ Open. 2012;2(2):e000635. Published 2012 Mar 11. doi:10.1136/bmjopen-2011-000635
3. Kadomura S, Takekuma Y, Sato Y, et al. Higher incidence of acute kidney injury in patients treated with piperacillin/tazobactam than in patients treated with cefepime: a single-center retrospective cohort study. J Pharm Health Care Sci. 2019;5:13. Published 2019 Jun 12. doi:10.1186/s40780-019-0142-6
4. Page RL 2nd, O’Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016;134(6):e32-e69. doi:10.1161/CIR.0000000000000426
5. Bozkurt B, Hershberger RE, Butler J, et al. 2021 ACC/AHA key data elements and definitions for heart failure: a report of the American College of Cardiology/American Heart Association task force on clinical data standards. J Am Coll Cardiol. 2021;77(16):2053-2150.
6. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 2021;143(8):e254-e743. doi:10.1161/CIR.0000000000000950
7. Merrem. Package insert. Pfizer Labs; 2021.
8. Keller GA, Alvarez PA, Ponte ML, et al. Drug-induced QTc interval prolongation: a multicenter study to detect drugs and clinical factors involved in every day practice. Curr Drug Saf. 2016;11(1):86-98. doi:10.2174/1574886311207040262
9. Wu S, Alikhil M, Forsyth R, Allen B. Impact of potentially unwarranted intravenous antibiotics targeting pulmonary infections in acute decompensated heart failure. J Pharm Technol. 2021;37(6):298-303. doi:10.1177/87551225211038020
10. Frisbee J, Heidel RH, Rasnake MS. Adverse outcomes associated with potentially inappropriate antibiotic use in heart failure admissions. Open Forum Infect Dis. 2019;6(6):ofz220. doi:10.1093/ofid/ofz220
1. Zosyn. Package insert. Wyeth Pharmaceuticals; 2020.
2. Jensen JU, Hein L, Lundgren B, et al. Kidney failure related to broad-spectrum antibiotics in critically ill patients: secondary end point results from a 1200 patient randomised trial. BMJ Open. 2012;2(2):e000635. Published 2012 Mar 11. doi:10.1136/bmjopen-2011-000635
3. Kadomura S, Takekuma Y, Sato Y, et al. Higher incidence of acute kidney injury in patients treated with piperacillin/tazobactam than in patients treated with cefepime: a single-center retrospective cohort study. J Pharm Health Care Sci. 2019;5:13. Published 2019 Jun 12. doi:10.1186/s40780-019-0142-6
4. Page RL 2nd, O’Bryant CL, Cheng D, et al. Drugs that may cause or exacerbate heart failure: a scientific statement from the American Heart Association. Circulation. 2016;134(6):e32-e69. doi:10.1161/CIR.0000000000000426
5. Bozkurt B, Hershberger RE, Butler J, et al. 2021 ACC/AHA key data elements and definitions for heart failure: a report of the American College of Cardiology/American Heart Association task force on clinical data standards. J Am Coll Cardiol. 2021;77(16):2053-2150.
6. Virani SS, Alonso A, Aparicio HJ, et al. Heart disease and stroke statistics-2021 update: a report from the American Heart Association. Circulation. 2021;143(8):e254-e743. doi:10.1161/CIR.0000000000000950
7. Merrem. Package insert. Pfizer Labs; 2021.
8. Keller GA, Alvarez PA, Ponte ML, et al. Drug-induced QTc interval prolongation: a multicenter study to detect drugs and clinical factors involved in every day practice. Curr Drug Saf. 2016;11(1):86-98. doi:10.2174/1574886311207040262
9. Wu S, Alikhil M, Forsyth R, Allen B. Impact of potentially unwarranted intravenous antibiotics targeting pulmonary infections in acute decompensated heart failure. J Pharm Technol. 2021;37(6):298-303. doi:10.1177/87551225211038020
10. Frisbee J, Heidel RH, Rasnake MS. Adverse outcomes associated with potentially inappropriate antibiotic use in heart failure admissions. Open Forum Infect Dis. 2019;6(6):ofz220. doi:10.1093/ofid/ofz220
Implementing Trustworthy AI in VA High Reliability Health Care Organizations
Artificial intelligence (AI) has lagged in health care but has considerable potential to improve quality, safety, clinician experience, and access to care. It is being tested in areas like billing, hospital operations, and preventing adverse events (eg, sepsis mortality) with some early success. However, there are still many barriers preventing the widespread use of AI, such as data problems, mismatched rewards, and workplace obstacles. Innovative projects, partnerships, better rewards, and more investment could remove barriers. Implemented reliably and safely, AI can add to what clinicians know, help them work faster, cut costs, and, most importantly, improve patient care.1
AI can potentially bring several clinical benefits, such as reducing the administrative strain on clinicians and granting them more time for direct patient care. It can also improve diagnostic accuracy by analyzing patient data and diagnostic images, providing differential diagnoses, and increasing access to care by providing medical information and essential online services to patients.2
High Reliability Organizations
High reliability health care organizations have considerable experience safely launching new programs. For example, the Patient Safety Adoption Framework gives practical tips for smoothly rolling out safety initiatives (Table 1). Developed with experts and diverse views, this framework has 5 key areas: leadership, culture and context, process, measurement, and person-centeredness. These address adoption problems, guide leaders step-by-step, and focus on leadership buy-in, safety culture, cooperation, and local customization. Checklists and tools make it systematic to go from ideas to action on patient safety.3
Leadership involves establishing organizational commitment behind new safety programs. This visible commitment signals importance and priorities to others. Leaders model desired behaviors and language around safety, allocate resources, remove obstacles, and keep initiatives energized over time through consistent messaging.4 Culture and context recognizes that safety culture differs across units and facilities. Local input tailors programs to fit and examines strengths to build on, like psychological safety. Surveys gauge the existing culture and its need for change. Process details how to plan, design, test, implement, and improve new safety practices and provides a phased roadmap from idea to results. Measurement collects data to drive improvement and show impact. Metrics track progress and allow benchmarking. Person-centeredness puts patients first in safety efforts through participation, education, and transparency.
The Veterans Health Administration piloted a comprehensive high reliability hospital (HRH) model. Over 3 years, the Veterans Health Administration focused on leadership, culture, and process improvement at a hospital. After initiating the model, the pilot hospital improved its safety culture, reported more minor safety issues, and reduced deaths and complications better than other hospitals. The high-reliability approach successfully instilled principles and improved culture and outcomes. The HRH model is set to be expanded to 18 more US Department of Veterans Affairs (VA) sites for further evaluation across diverse settings.5
Trustworthy AI Framework
AI systems are growing more powerful and widespread, including in health care. Unfortunately, irresponsible AI can introduce new harm. ChatGPT and other large language models, for example, sometimes are known to provide erroneous information in a compelling way. Clinicians and patients who use such programs can act on such information, which would lead to unforeseen negative consequences. Several frameworks on ethical AI have come from governmental groups.6-9 In 2023, the VA National AI Institute suggested a Trustworthy AI Framework based on core principles tailored for federal health care. The framework has 6 key principles: purposeful, effective and safe, secure and private, fair and equitable, transparent and explainable, and accountable and monitored (Table 2).10
First, AI must clearly help veterans while minimizing risks. To ensure purpose, the VA will assess patient and clinician needs and design AI that targets meaningful problems to avoid scope creep or feature bloat. For example, adding new features to the AI software after release can clutter and complicate the interface, making it difficult to use. Rigorous testing will confirm that AI meets intent prior to deployment. Second, AI is designed and checked for effectiveness, safety, and reliability. The VA pledges to monitor AI’s impact to ensure it performs as expected without unintended consequences. Algorithms will be stress tested across representative datasets and approval processes will screen for safety issues. Third, AI models are secured from vulnerabilities and misuse. Technical controls will prevent unauthorized access or changes to AI systems. Audits will check for appropriate internal usage per policies. Continual patches and upgrades will maintain security. Fourth, the VA manages AI for fairness, avoiding bias. They will proactively assess datasets and algorithms for potential biases based on protected attributes like race, gender, or age. Biased outputs will be addressed through techniques such as data augmentation, reweighting, and algorithm tweaks. Fifth, transparency explains AI’s role in care. Documentation will detail an AI system’s data sources, methodology, testing, limitations, and integration with clinical workflows. Clinicians and patients will receive education on interpreting AI outputs. Finally, the VA pledges to closely monitor AI systems to sustain trust. The VA will establish oversight processes to quickly identify any declines in reliability or unfair impacts on subgroups. AI models will be retrained as needed based on incoming data patterns.
Each Trustworthy AI Framework principle connects to others in existing frameworks. The purpose principle aligns with human-centric AI focused on benefits. Effectiveness and safety link to technical robustness and risk management principles. Security maps to privacy protection principles. Fairness connects to principles of avoiding bias and discrimination. Transparency corresponds with accountable and explainable AI. Monitoring and accountability tie back to governance principles. Overall, the VA framework aims to guide ethical AI based on context. It offers a model for managing risks and building trust in health care AI.
Combining VA principles with high-reliability safety principles can ensure that AI benefits veterans. The leadership and culture aspects will drive commitment to trustworthy AI practices. Leaders will communicate the importance of responsible AI through words and actions. Culture surveys can assess baseline awareness of AI ethics issues to target education. AI security and fairness will be emphasized as safety critical. The process aspect will institute policies and procedures to uphold AI principles through the project lifecycle. For example, structured testing processes will validate safety. Measurement will collect data on principles like transparency and fairness. Dashboards can track metrics like explainability and biases. A patient-centered approach will incorporate veteran perspectives on AI through participatory design and advisory councils. They can give input on AI explainability and potential biases based on their diverse backgrounds.
Conclusions
Joint principles will lead to successful AI that improves care while proactively managing risks. Involve leaders to stress the necessity of eliminating biases. Build security into the AI development process. Co-design AI transparency features with end users. Closely monitor the impact of AI across safety, fairness, and other principles. Adhering to both Trustworthy AI and high reliability organizations principles will earn veterans’ confidence. Health care organizations like the VA can integrate ethical AI safely via established frameworks. With responsible design and implementation, AI’s potential to enhance care quality, safety, and access can be realized.
Acknowledgments
We would like to acknowledge Joshua Mueller, Theo Tiffney, John Zachary, and Gil Alterovitz for their excellent work creating the VA Trustworthy Principles. This material is the result of work supported by resources and the use of facilities at the James A. Haley Veterans’ Hospital.
1. Sahni NR, Carrus B. Artificial intelligence in U.S. health care delivery. N Engl J Med. 2023;389(4):348-358. doi:10.1056/NEJMra2204673
2. Borkowski AA, Jakey CE, Mastorides SM, et al. Applications of ChatGPT and large language models in medicine and health care: benefits and pitfalls. Fed Pract. 2023;40(6):170-173. doi:10.12788/fp.0386
3. Moyal-Smith R, Margo J, Maloney FL, et al. The patient safety adoption framework: a practical framework to bridge the know-do gap. J Patient Saf. 2023;19(4):243-248. doi:10.1097/PTS.0000000000001118
4. Isaacks DB, Anderson TM, Moore SC, Patterson W, Govindan S. High reliability organization principles improve VA workplace burnout: the Truman THRIVE2 model. Am J Med Qual. 2021;36(6):422-428. doi:10.1097/01.JMQ.0000735516.35323.97
5. Sculli GL, Pendley-Louis R, Neily J, et al. A high-reliability organization framework for health care: a multiyear implementation strategy and associated outcomes. J Patient Saf. 2022;18(1):64-70. doi:10.1097/PTS.0000000000000788
6. National Institute of Standards and Technology. AI risk management framework. Accessed January 2, 2024. https://www.nist.gov/itl/ai-risk-management-framework
7. Executive Office of the President, Office of Science and Technology Policy. Blueprint for an AI Bill of Rights. Accessed January 11, 2024. https://www.whitehouse.gov/ostp/ai-bill-of-rights
8. Executive Office of the President. Executive Order 13960: promoting the use of trustworthy artificial intelligence in the federal government. Fed Regist. 2020;89(236):78939-78943.
9. Biden JR. Executive Order on the safe, secure, and trustworthy development and use of artificial intelligence. Published October 30, 2023. Accessed January 11, 2024. https://www.whitehouse.gov/briefing-room/presidential-actions/2023/10/30/executive-order-on-the-safe-secure-and-trustworthy-development-and-use-of-artificial-intelligence/
10. US Department of Veterans Affairs. Trustworthy AI. Accessed January 11, 2024. https://department.va.gov/ai/trustworthy/
Artificial intelligence (AI) has lagged in health care but has considerable potential to improve quality, safety, clinician experience, and access to care. It is being tested in areas like billing, hospital operations, and preventing adverse events (eg, sepsis mortality) with some early success. However, there are still many barriers preventing the widespread use of AI, such as data problems, mismatched rewards, and workplace obstacles. Innovative projects, partnerships, better rewards, and more investment could remove barriers. Implemented reliably and safely, AI can add to what clinicians know, help them work faster, cut costs, and, most importantly, improve patient care.1
AI can potentially bring several clinical benefits, such as reducing the administrative strain on clinicians and granting them more time for direct patient care. It can also improve diagnostic accuracy by analyzing patient data and diagnostic images, providing differential diagnoses, and increasing access to care by providing medical information and essential online services to patients.2
High Reliability Organizations
High reliability health care organizations have considerable experience safely launching new programs. For example, the Patient Safety Adoption Framework gives practical tips for smoothly rolling out safety initiatives (Table 1). Developed with experts and diverse views, this framework has 5 key areas: leadership, culture and context, process, measurement, and person-centeredness. These address adoption problems, guide leaders step-by-step, and focus on leadership buy-in, safety culture, cooperation, and local customization. Checklists and tools make it systematic to go from ideas to action on patient safety.3
Leadership involves establishing organizational commitment behind new safety programs. This visible commitment signals importance and priorities to others. Leaders model desired behaviors and language around safety, allocate resources, remove obstacles, and keep initiatives energized over time through consistent messaging.4 Culture and context recognizes that safety culture differs across units and facilities. Local input tailors programs to fit and examines strengths to build on, like psychological safety. Surveys gauge the existing culture and its need for change. Process details how to plan, design, test, implement, and improve new safety practices and provides a phased roadmap from idea to results. Measurement collects data to drive improvement and show impact. Metrics track progress and allow benchmarking. Person-centeredness puts patients first in safety efforts through participation, education, and transparency.
The Veterans Health Administration piloted a comprehensive high reliability hospital (HRH) model. Over 3 years, the Veterans Health Administration focused on leadership, culture, and process improvement at a hospital. After initiating the model, the pilot hospital improved its safety culture, reported more minor safety issues, and reduced deaths and complications better than other hospitals. The high-reliability approach successfully instilled principles and improved culture and outcomes. The HRH model is set to be expanded to 18 more US Department of Veterans Affairs (VA) sites for further evaluation across diverse settings.5
Trustworthy AI Framework
AI systems are growing more powerful and widespread, including in health care. Unfortunately, irresponsible AI can introduce new harm. ChatGPT and other large language models, for example, sometimes are known to provide erroneous information in a compelling way. Clinicians and patients who use such programs can act on such information, which would lead to unforeseen negative consequences. Several frameworks on ethical AI have come from governmental groups.6-9 In 2023, the VA National AI Institute suggested a Trustworthy AI Framework based on core principles tailored for federal health care. The framework has 6 key principles: purposeful, effective and safe, secure and private, fair and equitable, transparent and explainable, and accountable and monitored (Table 2).10
First, AI must clearly help veterans while minimizing risks. To ensure purpose, the VA will assess patient and clinician needs and design AI that targets meaningful problems to avoid scope creep or feature bloat. For example, adding new features to the AI software after release can clutter and complicate the interface, making it difficult to use. Rigorous testing will confirm that AI meets intent prior to deployment. Second, AI is designed and checked for effectiveness, safety, and reliability. The VA pledges to monitor AI’s impact to ensure it performs as expected without unintended consequences. Algorithms will be stress tested across representative datasets and approval processes will screen for safety issues. Third, AI models are secured from vulnerabilities and misuse. Technical controls will prevent unauthorized access or changes to AI systems. Audits will check for appropriate internal usage per policies. Continual patches and upgrades will maintain security. Fourth, the VA manages AI for fairness, avoiding bias. They will proactively assess datasets and algorithms for potential biases based on protected attributes like race, gender, or age. Biased outputs will be addressed through techniques such as data augmentation, reweighting, and algorithm tweaks. Fifth, transparency explains AI’s role in care. Documentation will detail an AI system’s data sources, methodology, testing, limitations, and integration with clinical workflows. Clinicians and patients will receive education on interpreting AI outputs. Finally, the VA pledges to closely monitor AI systems to sustain trust. The VA will establish oversight processes to quickly identify any declines in reliability or unfair impacts on subgroups. AI models will be retrained as needed based on incoming data patterns.
Each Trustworthy AI Framework principle connects to others in existing frameworks. The purpose principle aligns with human-centric AI focused on benefits. Effectiveness and safety link to technical robustness and risk management principles. Security maps to privacy protection principles. Fairness connects to principles of avoiding bias and discrimination. Transparency corresponds with accountable and explainable AI. Monitoring and accountability tie back to governance principles. Overall, the VA framework aims to guide ethical AI based on context. It offers a model for managing risks and building trust in health care AI.
Combining VA principles with high-reliability safety principles can ensure that AI benefits veterans. The leadership and culture aspects will drive commitment to trustworthy AI practices. Leaders will communicate the importance of responsible AI through words and actions. Culture surveys can assess baseline awareness of AI ethics issues to target education. AI security and fairness will be emphasized as safety critical. The process aspect will institute policies and procedures to uphold AI principles through the project lifecycle. For example, structured testing processes will validate safety. Measurement will collect data on principles like transparency and fairness. Dashboards can track metrics like explainability and biases. A patient-centered approach will incorporate veteran perspectives on AI through participatory design and advisory councils. They can give input on AI explainability and potential biases based on their diverse backgrounds.
Conclusions
Joint principles will lead to successful AI that improves care while proactively managing risks. Involve leaders to stress the necessity of eliminating biases. Build security into the AI development process. Co-design AI transparency features with end users. Closely monitor the impact of AI across safety, fairness, and other principles. Adhering to both Trustworthy AI and high reliability organizations principles will earn veterans’ confidence. Health care organizations like the VA can integrate ethical AI safely via established frameworks. With responsible design and implementation, AI’s potential to enhance care quality, safety, and access can be realized.
Acknowledgments
We would like to acknowledge Joshua Mueller, Theo Tiffney, John Zachary, and Gil Alterovitz for their excellent work creating the VA Trustworthy Principles. This material is the result of work supported by resources and the use of facilities at the James A. Haley Veterans’ Hospital.
Artificial intelligence (AI) has lagged in health care but has considerable potential to improve quality, safety, clinician experience, and access to care. It is being tested in areas like billing, hospital operations, and preventing adverse events (eg, sepsis mortality) with some early success. However, there are still many barriers preventing the widespread use of AI, such as data problems, mismatched rewards, and workplace obstacles. Innovative projects, partnerships, better rewards, and more investment could remove barriers. Implemented reliably and safely, AI can add to what clinicians know, help them work faster, cut costs, and, most importantly, improve patient care.1
AI can potentially bring several clinical benefits, such as reducing the administrative strain on clinicians and granting them more time for direct patient care. It can also improve diagnostic accuracy by analyzing patient data and diagnostic images, providing differential diagnoses, and increasing access to care by providing medical information and essential online services to patients.2
High Reliability Organizations
High reliability health care organizations have considerable experience safely launching new programs. For example, the Patient Safety Adoption Framework gives practical tips for smoothly rolling out safety initiatives (Table 1). Developed with experts and diverse views, this framework has 5 key areas: leadership, culture and context, process, measurement, and person-centeredness. These address adoption problems, guide leaders step-by-step, and focus on leadership buy-in, safety culture, cooperation, and local customization. Checklists and tools make it systematic to go from ideas to action on patient safety.3
Leadership involves establishing organizational commitment behind new safety programs. This visible commitment signals importance and priorities to others. Leaders model desired behaviors and language around safety, allocate resources, remove obstacles, and keep initiatives energized over time through consistent messaging.4 Culture and context recognizes that safety culture differs across units and facilities. Local input tailors programs to fit and examines strengths to build on, like psychological safety. Surveys gauge the existing culture and its need for change. Process details how to plan, design, test, implement, and improve new safety practices and provides a phased roadmap from idea to results. Measurement collects data to drive improvement and show impact. Metrics track progress and allow benchmarking. Person-centeredness puts patients first in safety efforts through participation, education, and transparency.
The Veterans Health Administration piloted a comprehensive high reliability hospital (HRH) model. Over 3 years, the Veterans Health Administration focused on leadership, culture, and process improvement at a hospital. After initiating the model, the pilot hospital improved its safety culture, reported more minor safety issues, and reduced deaths and complications better than other hospitals. The high-reliability approach successfully instilled principles and improved culture and outcomes. The HRH model is set to be expanded to 18 more US Department of Veterans Affairs (VA) sites for further evaluation across diverse settings.5
Trustworthy AI Framework
AI systems are growing more powerful and widespread, including in health care. Unfortunately, irresponsible AI can introduce new harm. ChatGPT and other large language models, for example, sometimes are known to provide erroneous information in a compelling way. Clinicians and patients who use such programs can act on such information, which would lead to unforeseen negative consequences. Several frameworks on ethical AI have come from governmental groups.6-9 In 2023, the VA National AI Institute suggested a Trustworthy AI Framework based on core principles tailored for federal health care. The framework has 6 key principles: purposeful, effective and safe, secure and private, fair and equitable, transparent and explainable, and accountable and monitored (Table 2).10
First, AI must clearly help veterans while minimizing risks. To ensure purpose, the VA will assess patient and clinician needs and design AI that targets meaningful problems to avoid scope creep or feature bloat. For example, adding new features to the AI software after release can clutter and complicate the interface, making it difficult to use. Rigorous testing will confirm that AI meets intent prior to deployment. Second, AI is designed and checked for effectiveness, safety, and reliability. The VA pledges to monitor AI’s impact to ensure it performs as expected without unintended consequences. Algorithms will be stress tested across representative datasets and approval processes will screen for safety issues. Third, AI models are secured from vulnerabilities and misuse. Technical controls will prevent unauthorized access or changes to AI systems. Audits will check for appropriate internal usage per policies. Continual patches and upgrades will maintain security. Fourth, the VA manages AI for fairness, avoiding bias. They will proactively assess datasets and algorithms for potential biases based on protected attributes like race, gender, or age. Biased outputs will be addressed through techniques such as data augmentation, reweighting, and algorithm tweaks. Fifth, transparency explains AI’s role in care. Documentation will detail an AI system’s data sources, methodology, testing, limitations, and integration with clinical workflows. Clinicians and patients will receive education on interpreting AI outputs. Finally, the VA pledges to closely monitor AI systems to sustain trust. The VA will establish oversight processes to quickly identify any declines in reliability or unfair impacts on subgroups. AI models will be retrained as needed based on incoming data patterns.
Each Trustworthy AI Framework principle connects to others in existing frameworks. The purpose principle aligns with human-centric AI focused on benefits. Effectiveness and safety link to technical robustness and risk management principles. Security maps to privacy protection principles. Fairness connects to principles of avoiding bias and discrimination. Transparency corresponds with accountable and explainable AI. Monitoring and accountability tie back to governance principles. Overall, the VA framework aims to guide ethical AI based on context. It offers a model for managing risks and building trust in health care AI.
Combining VA principles with high-reliability safety principles can ensure that AI benefits veterans. The leadership and culture aspects will drive commitment to trustworthy AI practices. Leaders will communicate the importance of responsible AI through words and actions. Culture surveys can assess baseline awareness of AI ethics issues to target education. AI security and fairness will be emphasized as safety critical. The process aspect will institute policies and procedures to uphold AI principles through the project lifecycle. For example, structured testing processes will validate safety. Measurement will collect data on principles like transparency and fairness. Dashboards can track metrics like explainability and biases. A patient-centered approach will incorporate veteran perspectives on AI through participatory design and advisory councils. They can give input on AI explainability and potential biases based on their diverse backgrounds.
Conclusions
Joint principles will lead to successful AI that improves care while proactively managing risks. Involve leaders to stress the necessity of eliminating biases. Build security into the AI development process. Co-design AI transparency features with end users. Closely monitor the impact of AI across safety, fairness, and other principles. Adhering to both Trustworthy AI and high reliability organizations principles will earn veterans’ confidence. Health care organizations like the VA can integrate ethical AI safely via established frameworks. With responsible design and implementation, AI’s potential to enhance care quality, safety, and access can be realized.
Acknowledgments
We would like to acknowledge Joshua Mueller, Theo Tiffney, John Zachary, and Gil Alterovitz for their excellent work creating the VA Trustworthy Principles. This material is the result of work supported by resources and the use of facilities at the James A. Haley Veterans’ Hospital.
1. Sahni NR, Carrus B. Artificial intelligence in U.S. health care delivery. N Engl J Med. 2023;389(4):348-358. doi:10.1056/NEJMra2204673
2. Borkowski AA, Jakey CE, Mastorides SM, et al. Applications of ChatGPT and large language models in medicine and health care: benefits and pitfalls. Fed Pract. 2023;40(6):170-173. doi:10.12788/fp.0386
3. Moyal-Smith R, Margo J, Maloney FL, et al. The patient safety adoption framework: a practical framework to bridge the know-do gap. J Patient Saf. 2023;19(4):243-248. doi:10.1097/PTS.0000000000001118
4. Isaacks DB, Anderson TM, Moore SC, Patterson W, Govindan S. High reliability organization principles improve VA workplace burnout: the Truman THRIVE2 model. Am J Med Qual. 2021;36(6):422-428. doi:10.1097/01.JMQ.0000735516.35323.97
5. Sculli GL, Pendley-Louis R, Neily J, et al. A high-reliability organization framework for health care: a multiyear implementation strategy and associated outcomes. J Patient Saf. 2022;18(1):64-70. doi:10.1097/PTS.0000000000000788
6. National Institute of Standards and Technology. AI risk management framework. Accessed January 2, 2024. https://www.nist.gov/itl/ai-risk-management-framework
7. Executive Office of the President, Office of Science and Technology Policy. Blueprint for an AI Bill of Rights. Accessed January 11, 2024. https://www.whitehouse.gov/ostp/ai-bill-of-rights
8. Executive Office of the President. Executive Order 13960: promoting the use of trustworthy artificial intelligence in the federal government. Fed Regist. 2020;89(236):78939-78943.
9. Biden JR. Executive Order on the safe, secure, and trustworthy development and use of artificial intelligence. Published October 30, 2023. Accessed January 11, 2024. https://www.whitehouse.gov/briefing-room/presidential-actions/2023/10/30/executive-order-on-the-safe-secure-and-trustworthy-development-and-use-of-artificial-intelligence/
10. US Department of Veterans Affairs. Trustworthy AI. Accessed January 11, 2024. https://department.va.gov/ai/trustworthy/
1. Sahni NR, Carrus B. Artificial intelligence in U.S. health care delivery. N Engl J Med. 2023;389(4):348-358. doi:10.1056/NEJMra2204673
2. Borkowski AA, Jakey CE, Mastorides SM, et al. Applications of ChatGPT and large language models in medicine and health care: benefits and pitfalls. Fed Pract. 2023;40(6):170-173. doi:10.12788/fp.0386
3. Moyal-Smith R, Margo J, Maloney FL, et al. The patient safety adoption framework: a practical framework to bridge the know-do gap. J Patient Saf. 2023;19(4):243-248. doi:10.1097/PTS.0000000000001118
4. Isaacks DB, Anderson TM, Moore SC, Patterson W, Govindan S. High reliability organization principles improve VA workplace burnout: the Truman THRIVE2 model. Am J Med Qual. 2021;36(6):422-428. doi:10.1097/01.JMQ.0000735516.35323.97
5. Sculli GL, Pendley-Louis R, Neily J, et al. A high-reliability organization framework for health care: a multiyear implementation strategy and associated outcomes. J Patient Saf. 2022;18(1):64-70. doi:10.1097/PTS.0000000000000788
6. National Institute of Standards and Technology. AI risk management framework. Accessed January 2, 2024. https://www.nist.gov/itl/ai-risk-management-framework
7. Executive Office of the President, Office of Science and Technology Policy. Blueprint for an AI Bill of Rights. Accessed January 11, 2024. https://www.whitehouse.gov/ostp/ai-bill-of-rights
8. Executive Office of the President. Executive Order 13960: promoting the use of trustworthy artificial intelligence in the federal government. Fed Regist. 2020;89(236):78939-78943.
9. Biden JR. Executive Order on the safe, secure, and trustworthy development and use of artificial intelligence. Published October 30, 2023. Accessed January 11, 2024. https://www.whitehouse.gov/briefing-room/presidential-actions/2023/10/30/executive-order-on-the-safe-secure-and-trustworthy-development-and-use-of-artificial-intelligence/
10. US Department of Veterans Affairs. Trustworthy AI. Accessed January 11, 2024. https://department.va.gov/ai/trustworthy/
Moving the Field FORWARD
As an organization, AGA has invested heavily in programs and initiatives to support the professional development of its members across career stages. This includes programs such as the AGA-AASLD Academic Skills Workshop (in which I was fortunate to participate in 2016), Women’s Leadership and Executive Leadership Conferences (with the Midwest Women in GI Regional Workshop taking place later this month), and the AGA Research Foundation Awards Program, which distributes over $2 million in funding annually to support promising early career and senior investigators.
AGA’s Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD) Program, which was first funded by the National Institutes of Health in 2018 and is focused on improving the diversity of the GI research workforce, is another shining example. Led by Dr. Byron Cryer and Dr. Sandra Quezada, the program recently welcomed its 3rd cohort of participants, including 14 mentees and 28 senior and near-peer mentors.
We are pleased to frequently highlight these programs in the pages of GI & Hepatology News, and hope you enjoy learning more about each of these initiatives in future issues.
In this month’s issue of GIHN, we highlight AGA’s newest Clinical Practice Guideline focused on management of pouchitis. We also report on the results of a recent RCT published in the New England Journal of Medicine demonstrating the efficacy of thalidomide as a treatment for recurrent bleeding due to small-intestinal angiodysplasia and summarize other key journal content impacting your clinical practice. In our February Member Spotlight, we feature Dr. Rajeev Jain of Texas Digestive Disease Consultants, a former AGA Governing Board member, and learn about his advocacy work to improve patient care and reduce physician burnout through insurance coverage and MOC reform. We hope you enjoy this, and all the exciting content included in our February issue!
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
As an organization, AGA has invested heavily in programs and initiatives to support the professional development of its members across career stages. This includes programs such as the AGA-AASLD Academic Skills Workshop (in which I was fortunate to participate in 2016), Women’s Leadership and Executive Leadership Conferences (with the Midwest Women in GI Regional Workshop taking place later this month), and the AGA Research Foundation Awards Program, which distributes over $2 million in funding annually to support promising early career and senior investigators.
AGA’s Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD) Program, which was first funded by the National Institutes of Health in 2018 and is focused on improving the diversity of the GI research workforce, is another shining example. Led by Dr. Byron Cryer and Dr. Sandra Quezada, the program recently welcomed its 3rd cohort of participants, including 14 mentees and 28 senior and near-peer mentors.
We are pleased to frequently highlight these programs in the pages of GI & Hepatology News, and hope you enjoy learning more about each of these initiatives in future issues.
In this month’s issue of GIHN, we highlight AGA’s newest Clinical Practice Guideline focused on management of pouchitis. We also report on the results of a recent RCT published in the New England Journal of Medicine demonstrating the efficacy of thalidomide as a treatment for recurrent bleeding due to small-intestinal angiodysplasia and summarize other key journal content impacting your clinical practice. In our February Member Spotlight, we feature Dr. Rajeev Jain of Texas Digestive Disease Consultants, a former AGA Governing Board member, and learn about his advocacy work to improve patient care and reduce physician burnout through insurance coverage and MOC reform. We hope you enjoy this, and all the exciting content included in our February issue!
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
As an organization, AGA has invested heavily in programs and initiatives to support the professional development of its members across career stages. This includes programs such as the AGA-AASLD Academic Skills Workshop (in which I was fortunate to participate in 2016), Women’s Leadership and Executive Leadership Conferences (with the Midwest Women in GI Regional Workshop taking place later this month), and the AGA Research Foundation Awards Program, which distributes over $2 million in funding annually to support promising early career and senior investigators.
AGA’s Fostering Opportunities Resulting in Workforce and Research Diversity (FORWARD) Program, which was first funded by the National Institutes of Health in 2018 and is focused on improving the diversity of the GI research workforce, is another shining example. Led by Dr. Byron Cryer and Dr. Sandra Quezada, the program recently welcomed its 3rd cohort of participants, including 14 mentees and 28 senior and near-peer mentors.
We are pleased to frequently highlight these programs in the pages of GI & Hepatology News, and hope you enjoy learning more about each of these initiatives in future issues.
In this month’s issue of GIHN, we highlight AGA’s newest Clinical Practice Guideline focused on management of pouchitis. We also report on the results of a recent RCT published in the New England Journal of Medicine demonstrating the efficacy of thalidomide as a treatment for recurrent bleeding due to small-intestinal angiodysplasia and summarize other key journal content impacting your clinical practice. In our February Member Spotlight, we feature Dr. Rajeev Jain of Texas Digestive Disease Consultants, a former AGA Governing Board member, and learn about his advocacy work to improve patient care and reduce physician burnout through insurance coverage and MOC reform. We hope you enjoy this, and all the exciting content included in our February issue!
Megan A. Adams, MD, JD, MSc
Editor-in-Chief