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Death anxiety in psychiatry and society: Facing our fears and embracing life
Our fear of death is exposed often in medicine. It is not uncommon to hear the last moments of a patient’s life described as a series of futile, sterile medical interventions that attempt to prolong that life in quasi-sadistic fashion. So much effort is placed in making sure that “everything necessary” is tried that less emphasis is made on providing a comfortable death.
It seems obvious that a profession dedicated to prolonging health would have difficulty confronting death. But it should also be natural for psychiatry to be the specialty able to integrate this discomfort within the medical psyche.
Yet, in training, we have noted much more time spent on the assessment of capacity in patients in order to refuse medical intervention than on time spent educating about the importance to die at the right time, as suggested by Friedrich Nietzsche.1 A psychiatry resident may graduate knowing dozens of questions to assess the ability of a family member to consider the risk, benefits, and alternatives of continued intubation in a comatose patient, but may feel very ill-equipped in discussing the meaning of a rightful life and a rightful death.
Death anxiety can also come outside the context of not having endured enough traumas or successes in one’s life, or not having lived life right. As poignantly described by Dostoevsky in his 1864 novella, “Notes from the Underground,” death anxiety can manifest as a result of the deterministic nature of life.2 Doing everything which is expected of us can feel like a betrayal of our one chance to have lived life authentically. This concept is also particularly familiar to physicians, who may have – in part – chosen their career path in response to a recommendation from their parents, rather than a more authentic feeling. Dostoevsky goads us to transgress, to act in a rebellious way, to truly feel alive. This can serve as a solution for death anxiety – if you are scared to die then live, live your fullest. Even if that means doing the unexpected or changing your path.
The fear of being forgotten after death can also drive many to pursue a legacy. Even a parent choosing to have children and teaching them values and belief systems is a way of leaving behind a mark on the world. For some, finding ways for being remembered after death – whether through fame, fortune, or having children, is a way of dealing with death anxiety.
The Mexican holiday “Dia de los Muertos,” or Day of the Dead, and the Japanese holiday “Obon” are examples from cultures where deceased ancestors are celebrated through rituals and offerings. Such cultures may relieve the anxiety of death by suggesting that one’s descendants will still care for the departed, and their legacy may remain.
Coping with death anxiety
For others, the road to recovery from death anxiety may take a completely different approach. Some may find comfort in the position that, to extinguish death anxiety, one should not live to the fullest but accept the tragic and mostly inconsequential aspects of life. The philosophical movement of “absurdism” addresses this perspective.
In our modern world, where we are so deeply attached to finding the cause and reason for things, absurdism reminds us that most of our lives and world do not have to make sense. While Albert Camus, arguably the most famous of the absurdist philosophers, encourages us to create meaning and transcend the tragedy and randomness of life,3 some patients can also find comfort in the idea that life is absurd, and thus one should not judge one’s own life and not fear own’s inevitable death.
Death anxiety can also be therapeutic. Especially in the existential tradition, one can enlist the fear of death for motivation. Many patients come to see us with a lack of motivation or drive. They feel paralyzed by their predicament and mental illness. As in the experiments of Martin Seligman, PhD, who shocked animals at random, a human exposed to repeated failure and abuse can get a sense of learned helplessness.4 Such patients can be very hard to reach, yet ultimately their despondence is no match for the reality that life will end. Reminding a patient that any day spent not feeling alive might as well be a metaphor for death is a challenging interpretation, but one that can lead to significant growth.
When considering the fear of death, psychiatry has generally taken the position that it is pathological, a form of anxiety. Psychiatry argues that one should strive to find fulfillment and joy in life. It thus may be a surprise to find that this is not a universally shared perspective.
In his 2010 book, author Thomas Ligotti argues on behalf of pessimistic and antinatalist views.5 Throughout the book he emphasizes the suffering that life can offer and argues against the endless pursuit of more life. To some psychiatrists, such arguments will be understood as insulting to our profession. Some may even interpret his texts as an argument in favor of ending one’s life.
However, psychiatrists must ask themselves “what are my answers to those arguments?” Mr. Ligotti’s book is a series of arguments against the idea that life will be pleasurable. Understanding those arguments and formulating a rebuttal would be an important process for any mental health provider. It is foolish to think that our patients do not have a rich and complicated relationship to death, and that none of our patients find death attractive in some ways. After all, accepting our fears as an important part of our body is a natural coping skill, which can also be taught.6
Part of the difficulty in discussing death and the fear of death may come from society’s resistance at having complicated conversations. It is not uncommon, currently, to include trigger warnings at the mention of discussions about death, even abstract ones. While we appreciate and encourage the articulation of feelings that a discussion about death may raise, we worry that such trigger warnings may be a form of censure that only makes society more resistant to talk about those important topics.
For another example of the avoidance of discussions about death, recall the “death panel” debates of 2009.7 When the U.S. government considered encouraging physicians to have discussions with their patients about end-of-life care, politicians and pundits decried that such discussions were “death panels,” and claimed they were an encouragement to patients to “cut [their] life short.” Such public projection of one’s anxiety about death has made it particularly difficult for psychiatry to make meaningful progress.
Acknowledging and addressing the fear
Death anxiety is such a common aspect of human life that most religions make some effort to address this fear. Many do so by offering a form of afterlife, often one described in idyllic fashion without anxiety.
Heaven, if one believes in it, is appealing for the person dreading death anxiety. Heaven is often described as being offered to those who have lived a rightful life, thus relieving the anxiety regarding the decisions one has made. Reincarnation can also be interpreted as another way of calming death anxiety, by promising a continual repetition of chances at getting life right. However, for many patients, religion doesn’t have the appeal that it once had.
Ultimately, the fear of death is a complex and multifaceted issue that can manifest in various ways. The medical profession, especially psychiatry, has a responsibility to address this fear in patients, but it also struggles with its own discomfort with the topic. The importance of providing a comfortable death is often overshadowed by the emphasis on prolonging life, which may manifest as a series of futile medical interventions.
The fear of death can be therapeutic and motivating, but it can also be pathological and lead to a lack of motivation or drive. The philosophical movements of absurdism and antinatalism offer alternative perspectives on death and life, and it is important for mental health providers to understand and engage with these views.
Yet acknowledging and addressing the fear of death is an important aspect of mental health care and a crucial part of the human experience.
Dr. Akkoor is a psychiatry resident at the University of California, San Diego. She is interested in immigrant mental health, ethics, consultation-liaison psychiatry, and medical education. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Badre and Dr. Akkoor have no conflicts of interest.
References
1. Nietzsche F. Thus Spoke Zarathustra. 1883-1892.
2. Dostoevsky F. Notes from the Underground. 1864.
3. Camus A. The Plague. 1947.
4. Seligman M. Helplessness: On depression, development, and death. 1975.
5. Ligotti T. The Conspiracy Against the Human Race. 2010.
6. Hayes SC. Behav Ther. 2016 Nov;47(6):869-85. doi: 10.1016/j.beth.2016.11.006.
7. Nyhan B. The Forum. 2010 April 27;8(1). doi: 10.2202/1540-8884.1354.
Our fear of death is exposed often in medicine. It is not uncommon to hear the last moments of a patient’s life described as a series of futile, sterile medical interventions that attempt to prolong that life in quasi-sadistic fashion. So much effort is placed in making sure that “everything necessary” is tried that less emphasis is made on providing a comfortable death.
It seems obvious that a profession dedicated to prolonging health would have difficulty confronting death. But it should also be natural for psychiatry to be the specialty able to integrate this discomfort within the medical psyche.
Yet, in training, we have noted much more time spent on the assessment of capacity in patients in order to refuse medical intervention than on time spent educating about the importance to die at the right time, as suggested by Friedrich Nietzsche.1 A psychiatry resident may graduate knowing dozens of questions to assess the ability of a family member to consider the risk, benefits, and alternatives of continued intubation in a comatose patient, but may feel very ill-equipped in discussing the meaning of a rightful life and a rightful death.
Death anxiety can also come outside the context of not having endured enough traumas or successes in one’s life, or not having lived life right. As poignantly described by Dostoevsky in his 1864 novella, “Notes from the Underground,” death anxiety can manifest as a result of the deterministic nature of life.2 Doing everything which is expected of us can feel like a betrayal of our one chance to have lived life authentically. This concept is also particularly familiar to physicians, who may have – in part – chosen their career path in response to a recommendation from their parents, rather than a more authentic feeling. Dostoevsky goads us to transgress, to act in a rebellious way, to truly feel alive. This can serve as a solution for death anxiety – if you are scared to die then live, live your fullest. Even if that means doing the unexpected or changing your path.
The fear of being forgotten after death can also drive many to pursue a legacy. Even a parent choosing to have children and teaching them values and belief systems is a way of leaving behind a mark on the world. For some, finding ways for being remembered after death – whether through fame, fortune, or having children, is a way of dealing with death anxiety.
The Mexican holiday “Dia de los Muertos,” or Day of the Dead, and the Japanese holiday “Obon” are examples from cultures where deceased ancestors are celebrated through rituals and offerings. Such cultures may relieve the anxiety of death by suggesting that one’s descendants will still care for the departed, and their legacy may remain.
Coping with death anxiety
For others, the road to recovery from death anxiety may take a completely different approach. Some may find comfort in the position that, to extinguish death anxiety, one should not live to the fullest but accept the tragic and mostly inconsequential aspects of life. The philosophical movement of “absurdism” addresses this perspective.
In our modern world, where we are so deeply attached to finding the cause and reason for things, absurdism reminds us that most of our lives and world do not have to make sense. While Albert Camus, arguably the most famous of the absurdist philosophers, encourages us to create meaning and transcend the tragedy and randomness of life,3 some patients can also find comfort in the idea that life is absurd, and thus one should not judge one’s own life and not fear own’s inevitable death.
Death anxiety can also be therapeutic. Especially in the existential tradition, one can enlist the fear of death for motivation. Many patients come to see us with a lack of motivation or drive. They feel paralyzed by their predicament and mental illness. As in the experiments of Martin Seligman, PhD, who shocked animals at random, a human exposed to repeated failure and abuse can get a sense of learned helplessness.4 Such patients can be very hard to reach, yet ultimately their despondence is no match for the reality that life will end. Reminding a patient that any day spent not feeling alive might as well be a metaphor for death is a challenging interpretation, but one that can lead to significant growth.
When considering the fear of death, psychiatry has generally taken the position that it is pathological, a form of anxiety. Psychiatry argues that one should strive to find fulfillment and joy in life. It thus may be a surprise to find that this is not a universally shared perspective.
In his 2010 book, author Thomas Ligotti argues on behalf of pessimistic and antinatalist views.5 Throughout the book he emphasizes the suffering that life can offer and argues against the endless pursuit of more life. To some psychiatrists, such arguments will be understood as insulting to our profession. Some may even interpret his texts as an argument in favor of ending one’s life.
However, psychiatrists must ask themselves “what are my answers to those arguments?” Mr. Ligotti’s book is a series of arguments against the idea that life will be pleasurable. Understanding those arguments and formulating a rebuttal would be an important process for any mental health provider. It is foolish to think that our patients do not have a rich and complicated relationship to death, and that none of our patients find death attractive in some ways. After all, accepting our fears as an important part of our body is a natural coping skill, which can also be taught.6
Part of the difficulty in discussing death and the fear of death may come from society’s resistance at having complicated conversations. It is not uncommon, currently, to include trigger warnings at the mention of discussions about death, even abstract ones. While we appreciate and encourage the articulation of feelings that a discussion about death may raise, we worry that such trigger warnings may be a form of censure that only makes society more resistant to talk about those important topics.
For another example of the avoidance of discussions about death, recall the “death panel” debates of 2009.7 When the U.S. government considered encouraging physicians to have discussions with their patients about end-of-life care, politicians and pundits decried that such discussions were “death panels,” and claimed they were an encouragement to patients to “cut [their] life short.” Such public projection of one’s anxiety about death has made it particularly difficult for psychiatry to make meaningful progress.
Acknowledging and addressing the fear
Death anxiety is such a common aspect of human life that most religions make some effort to address this fear. Many do so by offering a form of afterlife, often one described in idyllic fashion without anxiety.
Heaven, if one believes in it, is appealing for the person dreading death anxiety. Heaven is often described as being offered to those who have lived a rightful life, thus relieving the anxiety regarding the decisions one has made. Reincarnation can also be interpreted as another way of calming death anxiety, by promising a continual repetition of chances at getting life right. However, for many patients, religion doesn’t have the appeal that it once had.
Ultimately, the fear of death is a complex and multifaceted issue that can manifest in various ways. The medical profession, especially psychiatry, has a responsibility to address this fear in patients, but it also struggles with its own discomfort with the topic. The importance of providing a comfortable death is often overshadowed by the emphasis on prolonging life, which may manifest as a series of futile medical interventions.
The fear of death can be therapeutic and motivating, but it can also be pathological and lead to a lack of motivation or drive. The philosophical movements of absurdism and antinatalism offer alternative perspectives on death and life, and it is important for mental health providers to understand and engage with these views.
Yet acknowledging and addressing the fear of death is an important aspect of mental health care and a crucial part of the human experience.
Dr. Akkoor is a psychiatry resident at the University of California, San Diego. She is interested in immigrant mental health, ethics, consultation-liaison psychiatry, and medical education. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Badre and Dr. Akkoor have no conflicts of interest.
References
1. Nietzsche F. Thus Spoke Zarathustra. 1883-1892.
2. Dostoevsky F. Notes from the Underground. 1864.
3. Camus A. The Plague. 1947.
4. Seligman M. Helplessness: On depression, development, and death. 1975.
5. Ligotti T. The Conspiracy Against the Human Race. 2010.
6. Hayes SC. Behav Ther. 2016 Nov;47(6):869-85. doi: 10.1016/j.beth.2016.11.006.
7. Nyhan B. The Forum. 2010 April 27;8(1). doi: 10.2202/1540-8884.1354.
Our fear of death is exposed often in medicine. It is not uncommon to hear the last moments of a patient’s life described as a series of futile, sterile medical interventions that attempt to prolong that life in quasi-sadistic fashion. So much effort is placed in making sure that “everything necessary” is tried that less emphasis is made on providing a comfortable death.
It seems obvious that a profession dedicated to prolonging health would have difficulty confronting death. But it should also be natural for psychiatry to be the specialty able to integrate this discomfort within the medical psyche.
Yet, in training, we have noted much more time spent on the assessment of capacity in patients in order to refuse medical intervention than on time spent educating about the importance to die at the right time, as suggested by Friedrich Nietzsche.1 A psychiatry resident may graduate knowing dozens of questions to assess the ability of a family member to consider the risk, benefits, and alternatives of continued intubation in a comatose patient, but may feel very ill-equipped in discussing the meaning of a rightful life and a rightful death.
Death anxiety can also come outside the context of not having endured enough traumas or successes in one’s life, or not having lived life right. As poignantly described by Dostoevsky in his 1864 novella, “Notes from the Underground,” death anxiety can manifest as a result of the deterministic nature of life.2 Doing everything which is expected of us can feel like a betrayal of our one chance to have lived life authentically. This concept is also particularly familiar to physicians, who may have – in part – chosen their career path in response to a recommendation from their parents, rather than a more authentic feeling. Dostoevsky goads us to transgress, to act in a rebellious way, to truly feel alive. This can serve as a solution for death anxiety – if you are scared to die then live, live your fullest. Even if that means doing the unexpected or changing your path.
The fear of being forgotten after death can also drive many to pursue a legacy. Even a parent choosing to have children and teaching them values and belief systems is a way of leaving behind a mark on the world. For some, finding ways for being remembered after death – whether through fame, fortune, or having children, is a way of dealing with death anxiety.
The Mexican holiday “Dia de los Muertos,” or Day of the Dead, and the Japanese holiday “Obon” are examples from cultures where deceased ancestors are celebrated through rituals and offerings. Such cultures may relieve the anxiety of death by suggesting that one’s descendants will still care for the departed, and their legacy may remain.
Coping with death anxiety
For others, the road to recovery from death anxiety may take a completely different approach. Some may find comfort in the position that, to extinguish death anxiety, one should not live to the fullest but accept the tragic and mostly inconsequential aspects of life. The philosophical movement of “absurdism” addresses this perspective.
In our modern world, where we are so deeply attached to finding the cause and reason for things, absurdism reminds us that most of our lives and world do not have to make sense. While Albert Camus, arguably the most famous of the absurdist philosophers, encourages us to create meaning and transcend the tragedy and randomness of life,3 some patients can also find comfort in the idea that life is absurd, and thus one should not judge one’s own life and not fear own’s inevitable death.
Death anxiety can also be therapeutic. Especially in the existential tradition, one can enlist the fear of death for motivation. Many patients come to see us with a lack of motivation or drive. They feel paralyzed by their predicament and mental illness. As in the experiments of Martin Seligman, PhD, who shocked animals at random, a human exposed to repeated failure and abuse can get a sense of learned helplessness.4 Such patients can be very hard to reach, yet ultimately their despondence is no match for the reality that life will end. Reminding a patient that any day spent not feeling alive might as well be a metaphor for death is a challenging interpretation, but one that can lead to significant growth.
When considering the fear of death, psychiatry has generally taken the position that it is pathological, a form of anxiety. Psychiatry argues that one should strive to find fulfillment and joy in life. It thus may be a surprise to find that this is not a universally shared perspective.
In his 2010 book, author Thomas Ligotti argues on behalf of pessimistic and antinatalist views.5 Throughout the book he emphasizes the suffering that life can offer and argues against the endless pursuit of more life. To some psychiatrists, such arguments will be understood as insulting to our profession. Some may even interpret his texts as an argument in favor of ending one’s life.
However, psychiatrists must ask themselves “what are my answers to those arguments?” Mr. Ligotti’s book is a series of arguments against the idea that life will be pleasurable. Understanding those arguments and formulating a rebuttal would be an important process for any mental health provider. It is foolish to think that our patients do not have a rich and complicated relationship to death, and that none of our patients find death attractive in some ways. After all, accepting our fears as an important part of our body is a natural coping skill, which can also be taught.6
Part of the difficulty in discussing death and the fear of death may come from society’s resistance at having complicated conversations. It is not uncommon, currently, to include trigger warnings at the mention of discussions about death, even abstract ones. While we appreciate and encourage the articulation of feelings that a discussion about death may raise, we worry that such trigger warnings may be a form of censure that only makes society more resistant to talk about those important topics.
For another example of the avoidance of discussions about death, recall the “death panel” debates of 2009.7 When the U.S. government considered encouraging physicians to have discussions with their patients about end-of-life care, politicians and pundits decried that such discussions were “death panels,” and claimed they were an encouragement to patients to “cut [their] life short.” Such public projection of one’s anxiety about death has made it particularly difficult for psychiatry to make meaningful progress.
Acknowledging and addressing the fear
Death anxiety is such a common aspect of human life that most religions make some effort to address this fear. Many do so by offering a form of afterlife, often one described in idyllic fashion without anxiety.
Heaven, if one believes in it, is appealing for the person dreading death anxiety. Heaven is often described as being offered to those who have lived a rightful life, thus relieving the anxiety regarding the decisions one has made. Reincarnation can also be interpreted as another way of calming death anxiety, by promising a continual repetition of chances at getting life right. However, for many patients, religion doesn’t have the appeal that it once had.
Ultimately, the fear of death is a complex and multifaceted issue that can manifest in various ways. The medical profession, especially psychiatry, has a responsibility to address this fear in patients, but it also struggles with its own discomfort with the topic. The importance of providing a comfortable death is often overshadowed by the emphasis on prolonging life, which may manifest as a series of futile medical interventions.
The fear of death can be therapeutic and motivating, but it can also be pathological and lead to a lack of motivation or drive. The philosophical movements of absurdism and antinatalism offer alternative perspectives on death and life, and it is important for mental health providers to understand and engage with these views.
Yet acknowledging and addressing the fear of death is an important aspect of mental health care and a crucial part of the human experience.
Dr. Akkoor is a psychiatry resident at the University of California, San Diego. She is interested in immigrant mental health, ethics, consultation-liaison psychiatry, and medical education. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. Dr. Badre and Dr. Akkoor have no conflicts of interest.
References
1. Nietzsche F. Thus Spoke Zarathustra. 1883-1892.
2. Dostoevsky F. Notes from the Underground. 1864.
3. Camus A. The Plague. 1947.
4. Seligman M. Helplessness: On depression, development, and death. 1975.
5. Ligotti T. The Conspiracy Against the Human Race. 2010.
6. Hayes SC. Behav Ther. 2016 Nov;47(6):869-85. doi: 10.1016/j.beth.2016.11.006.
7. Nyhan B. The Forum. 2010 April 27;8(1). doi: 10.2202/1540-8884.1354.
Parsing the split-decision victory for biologics in COPD
It’s tough to keep up with the proliferation of monoclonal antibodies. Seems every day I’m confronted by a patient who’s using a new drug with a name ending in “mab.” That drug blocks a cellular receptor I haven’t heard of that’s involved in a cascade of interactions I haven’t thought about since medical school. The resulting disruption reduces disease burden, typically at great expense to the medical system, the patient, or both. We’ve truly entered the era of precision medicine. It’s not enough to understand disease; you also must know its heterogeneous expression so that you can prescribe the ‘mab that targets the biology responsible for variants in behavior. All diseases are, in fact, syndromes. This isn’t a bad thing, but it’s a challenge.
A series of ‘mabs have been approved for treating type 2 high (TH2) or eosinophilic asthma. We refer to this group of ‘mabs generically as biologics. The group includes omalizumab, mepolizumab, dupilumab, benralizumab, reslizumab, and tezepelumab. While mechanism of action varies slightly across drugs, the biologics all target a specific arm of the immune system. Efficacy is linearly related to serum eosinophil count and there’s little clinically or pharmacologically to distinguish one from another. Of course, no head-to-head comparisons of efficacy are available and there’s no financial incentive for them to be performed.
Latest research
A new randomized controlled trial (RCT) of dupilumab for chronic obstructive pulmonary disease (COPD) adds to the aforementioned biologic knowledge base. Turns out it works as long as the patients are carefully selected. Researchers enrolled GOLD D (or E depending on which iteration of the GOLD Statement you use) patients on triple inhaler therapy (inhaled corticosteroids [ICS]/long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) with two moderate exacerbations or one exacerbation requiring hospitalization in the past year. Blood eosinophil counts were > 300 cells/mcL and chronic bronchitis was present clinically. The primary and multiple secondary outcomes were improved with dupilumab.
This is welcome news. I’ve treated countless patients with severe COPD who have repeated exacerbations despite my efforts to prevent them. These patients are on ICS/LABA/LAMA and azithromycin or roflumilast, and occasionally both. While every COPD guideline known to man forbids using chronic oral corticosteroids (OCS), I’ve prescribed them repeatedly because the benefits to keeping a recalcitrant, exacerbating patient out of the hospital seem to outweigh OCS risks. It would be nice to have a better option. Although we were taught that they were immutably distinct in medical school, every first-year pulmonary fellow knows that asthma and COPD share more similarities than differences, so it makes sense that proven asthma therapies would work for some patients with COPD.
However, the dupilumab study must be placed in context. Past studies haven’t been as positive. In 2017, two separate RCTs found that mepolizumab reduced the annual rate of moderate to severe exacerbations (primary outcome) in one trial but not the other. Interpretation gets more complicated when broken down by intention to treat (ITT) vs. modified ITT and when secondary outcomes are considered. Sparing you those details, this trial does not instill confidence, leading the Food and Drug Administration to refuse approval for mepolizumab for COPD. A second RCT of benralizumab for COPD was published in 2019. Much less cognitive load was required to interpret this one; it was negative. FDA approval was not requested.
Looking through the trial designs for the three RCTs of biologics for COPD, I couldn’t find major differences that could explain the discordant results. Sample size and enrollment criteria were similar. As stated, I don’t believe that the biologic data in asthma allow for predicting efficacy in one eosinophilic patient vs. another and I assume the same would be true for COPD. All three trials found that eosinophils were eliminated, so responses were biologically equivalent.
Key takeaways
If trial design and pharmacology don’t account for the disparate outcomes, how do we explain them? More important, how do we translate these trials into clinical practice? I looked for a review or editorial by a scientist-clinician smarter than I so I could steal their ideas and express them as pedantic euphemisms here. I found it curious that I was unable to find one. A recent publication in the American Journal of Respiratory and Critical Care Medicine suggests that the answer lies within the complex lattice of eosinophil subtypes, but I’m unqualified to judge the veracity of this “phenotype within a phenotype” theory.
More trials in COPD are being done. We should have results on tezepelumab, that great savior that may cover noneosinophilic asthma phenotypes, within the next few years. Until then, we’re stuck defying guidelines with the anachronistic use of OCS for the COPD patient who exacerbates through ICS/LABA/LAMA, roflumilast, and azithromycin.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported receiving income from CHEST College, Metapharm, and WebMD.
A version of this article first appeared on Medscape.com.
It’s tough to keep up with the proliferation of monoclonal antibodies. Seems every day I’m confronted by a patient who’s using a new drug with a name ending in “mab.” That drug blocks a cellular receptor I haven’t heard of that’s involved in a cascade of interactions I haven’t thought about since medical school. The resulting disruption reduces disease burden, typically at great expense to the medical system, the patient, or both. We’ve truly entered the era of precision medicine. It’s not enough to understand disease; you also must know its heterogeneous expression so that you can prescribe the ‘mab that targets the biology responsible for variants in behavior. All diseases are, in fact, syndromes. This isn’t a bad thing, but it’s a challenge.
A series of ‘mabs have been approved for treating type 2 high (TH2) or eosinophilic asthma. We refer to this group of ‘mabs generically as biologics. The group includes omalizumab, mepolizumab, dupilumab, benralizumab, reslizumab, and tezepelumab. While mechanism of action varies slightly across drugs, the biologics all target a specific arm of the immune system. Efficacy is linearly related to serum eosinophil count and there’s little clinically or pharmacologically to distinguish one from another. Of course, no head-to-head comparisons of efficacy are available and there’s no financial incentive for them to be performed.
Latest research
A new randomized controlled trial (RCT) of dupilumab for chronic obstructive pulmonary disease (COPD) adds to the aforementioned biologic knowledge base. Turns out it works as long as the patients are carefully selected. Researchers enrolled GOLD D (or E depending on which iteration of the GOLD Statement you use) patients on triple inhaler therapy (inhaled corticosteroids [ICS]/long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) with two moderate exacerbations or one exacerbation requiring hospitalization in the past year. Blood eosinophil counts were > 300 cells/mcL and chronic bronchitis was present clinically. The primary and multiple secondary outcomes were improved with dupilumab.
This is welcome news. I’ve treated countless patients with severe COPD who have repeated exacerbations despite my efforts to prevent them. These patients are on ICS/LABA/LAMA and azithromycin or roflumilast, and occasionally both. While every COPD guideline known to man forbids using chronic oral corticosteroids (OCS), I’ve prescribed them repeatedly because the benefits to keeping a recalcitrant, exacerbating patient out of the hospital seem to outweigh OCS risks. It would be nice to have a better option. Although we were taught that they were immutably distinct in medical school, every first-year pulmonary fellow knows that asthma and COPD share more similarities than differences, so it makes sense that proven asthma therapies would work for some patients with COPD.
However, the dupilumab study must be placed in context. Past studies haven’t been as positive. In 2017, two separate RCTs found that mepolizumab reduced the annual rate of moderate to severe exacerbations (primary outcome) in one trial but not the other. Interpretation gets more complicated when broken down by intention to treat (ITT) vs. modified ITT and when secondary outcomes are considered. Sparing you those details, this trial does not instill confidence, leading the Food and Drug Administration to refuse approval for mepolizumab for COPD. A second RCT of benralizumab for COPD was published in 2019. Much less cognitive load was required to interpret this one; it was negative. FDA approval was not requested.
Looking through the trial designs for the three RCTs of biologics for COPD, I couldn’t find major differences that could explain the discordant results. Sample size and enrollment criteria were similar. As stated, I don’t believe that the biologic data in asthma allow for predicting efficacy in one eosinophilic patient vs. another and I assume the same would be true for COPD. All three trials found that eosinophils were eliminated, so responses were biologically equivalent.
Key takeaways
If trial design and pharmacology don’t account for the disparate outcomes, how do we explain them? More important, how do we translate these trials into clinical practice? I looked for a review or editorial by a scientist-clinician smarter than I so I could steal their ideas and express them as pedantic euphemisms here. I found it curious that I was unable to find one. A recent publication in the American Journal of Respiratory and Critical Care Medicine suggests that the answer lies within the complex lattice of eosinophil subtypes, but I’m unqualified to judge the veracity of this “phenotype within a phenotype” theory.
More trials in COPD are being done. We should have results on tezepelumab, that great savior that may cover noneosinophilic asthma phenotypes, within the next few years. Until then, we’re stuck defying guidelines with the anachronistic use of OCS for the COPD patient who exacerbates through ICS/LABA/LAMA, roflumilast, and azithromycin.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported receiving income from CHEST College, Metapharm, and WebMD.
A version of this article first appeared on Medscape.com.
It’s tough to keep up with the proliferation of monoclonal antibodies. Seems every day I’m confronted by a patient who’s using a new drug with a name ending in “mab.” That drug blocks a cellular receptor I haven’t heard of that’s involved in a cascade of interactions I haven’t thought about since medical school. The resulting disruption reduces disease burden, typically at great expense to the medical system, the patient, or both. We’ve truly entered the era of precision medicine. It’s not enough to understand disease; you also must know its heterogeneous expression so that you can prescribe the ‘mab that targets the biology responsible for variants in behavior. All diseases are, in fact, syndromes. This isn’t a bad thing, but it’s a challenge.
A series of ‘mabs have been approved for treating type 2 high (TH2) or eosinophilic asthma. We refer to this group of ‘mabs generically as biologics. The group includes omalizumab, mepolizumab, dupilumab, benralizumab, reslizumab, and tezepelumab. While mechanism of action varies slightly across drugs, the biologics all target a specific arm of the immune system. Efficacy is linearly related to serum eosinophil count and there’s little clinically or pharmacologically to distinguish one from another. Of course, no head-to-head comparisons of efficacy are available and there’s no financial incentive for them to be performed.
Latest research
A new randomized controlled trial (RCT) of dupilumab for chronic obstructive pulmonary disease (COPD) adds to the aforementioned biologic knowledge base. Turns out it works as long as the patients are carefully selected. Researchers enrolled GOLD D (or E depending on which iteration of the GOLD Statement you use) patients on triple inhaler therapy (inhaled corticosteroids [ICS]/long-acting beta-agonist [LABA]/long-acting muscarinic antagonist [LAMA]) with two moderate exacerbations or one exacerbation requiring hospitalization in the past year. Blood eosinophil counts were > 300 cells/mcL and chronic bronchitis was present clinically. The primary and multiple secondary outcomes were improved with dupilumab.
This is welcome news. I’ve treated countless patients with severe COPD who have repeated exacerbations despite my efforts to prevent them. These patients are on ICS/LABA/LAMA and azithromycin or roflumilast, and occasionally both. While every COPD guideline known to man forbids using chronic oral corticosteroids (OCS), I’ve prescribed them repeatedly because the benefits to keeping a recalcitrant, exacerbating patient out of the hospital seem to outweigh OCS risks. It would be nice to have a better option. Although we were taught that they were immutably distinct in medical school, every first-year pulmonary fellow knows that asthma and COPD share more similarities than differences, so it makes sense that proven asthma therapies would work for some patients with COPD.
However, the dupilumab study must be placed in context. Past studies haven’t been as positive. In 2017, two separate RCTs found that mepolizumab reduced the annual rate of moderate to severe exacerbations (primary outcome) in one trial but not the other. Interpretation gets more complicated when broken down by intention to treat (ITT) vs. modified ITT and when secondary outcomes are considered. Sparing you those details, this trial does not instill confidence, leading the Food and Drug Administration to refuse approval for mepolizumab for COPD. A second RCT of benralizumab for COPD was published in 2019. Much less cognitive load was required to interpret this one; it was negative. FDA approval was not requested.
Looking through the trial designs for the three RCTs of biologics for COPD, I couldn’t find major differences that could explain the discordant results. Sample size and enrollment criteria were similar. As stated, I don’t believe that the biologic data in asthma allow for predicting efficacy in one eosinophilic patient vs. another and I assume the same would be true for COPD. All three trials found that eosinophils were eliminated, so responses were biologically equivalent.
Key takeaways
If trial design and pharmacology don’t account for the disparate outcomes, how do we explain them? More important, how do we translate these trials into clinical practice? I looked for a review or editorial by a scientist-clinician smarter than I so I could steal their ideas and express them as pedantic euphemisms here. I found it curious that I was unable to find one. A recent publication in the American Journal of Respiratory and Critical Care Medicine suggests that the answer lies within the complex lattice of eosinophil subtypes, but I’m unqualified to judge the veracity of this “phenotype within a phenotype” theory.
More trials in COPD are being done. We should have results on tezepelumab, that great savior that may cover noneosinophilic asthma phenotypes, within the next few years. Until then, we’re stuck defying guidelines with the anachronistic use of OCS for the COPD patient who exacerbates through ICS/LABA/LAMA, roflumilast, and azithromycin.
Dr. Holley is professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington. He reported receiving income from CHEST College, Metapharm, and WebMD.
A version of this article first appeared on Medscape.com.
Oral GLP-1 agonists could be game changers for obesity
The advent of subcutaneously injectable glucagonlike peptide–1 (GLP-1) receptor agonists for the management of type 2 diabetes during 2005 was arguably one of the greatest therapeutic advances for the condition since metformin.
I was an early advocate of the class, given its potent glucose-lowering efficacy, secondary benefits of significant weight reduction, and a low risk for hypoglycemia (if not used alongside sulfonylureas or insulin).
During 2016, the first cardiovascular outcomes trial for a GLP-1 agonist, in the form of the LEADER study, was reported. These trials were mandated by the Food and Drug Administration in the aftermath of the rosiglitazone debacle in which the type 2 diabetes drug had its use restricted because of cardiovascular events attributed to it in a meta-analysis. These events weren’t seen in a subsequent trial, and the FDA’s restrictions were later lifted.
LEADER examined the once-daily GLP-1 agonist liraglutide and showed that, in addition to its glucose-lowering effects, liraglutide brought cardiovascular benefits to the table. Moreover, during 2019, the REWIND trial, the cardiovascular outcome trial for once-weekly subcutaneous dulaglutide, revealed the same cardiovascular benefits but also demonstrated a lower incidence of macroalbuminuria, albeit with no significant improvements in hard renal endpoints such as estimated glomerular filtration decline or rates of dialysis.
Despite these compelling benefits, the uptake of GLP-1 agonists has always been slower than that of other compelling agents such as the sodium-glucose cotransporter 2 inhibitors, mainly because the latter are oral drugs, while GLP-1 agonists were initially injectable medications. This difference has proven to be a barrier for patients and clinicians alike.
However, in 2019, oral semaglutide, in doses of 7 mg and 14 mg, was approved by the FDA as the first (and still only) commercially available oral GLP-1 agonist to improve glycemic control in adults with type 2 diabetes. This approval was hailed as a “game changer” at the time. The treatment had no proven cardiovascular benefits, only lack of cardiovascular harm in PIONEER 6. The SOUL cardiovascular outcome trial for oral semaglutide in doses of 7 mg and 14 mg is due to be completed during 2024. But semaglutide certainly had compelling glucose-lowering efficacy and secondary benefits of significant weight loss similar to those of its injectable counterparts.
Cardiovascular benefits of injectable semaglutide for type 2 diabetes were demonstrated in the SUSTAIN-6 trial in 2016, and the U.S. label for Ozempic was amended accordingly in 2020.
Again, I was an early adopter of oral semaglutide, and it has been great for my patients with type 2 diabetes to have the option of a noninjectable GLP-1 agonist. However, it is not without its drawbacks: Oral semaglutide must be taken on an empty stomach, at least 30 minutes before any other food, drink, or medication, and with no more than 120 mL water to maximize absorption and bioavailability.
I am of South Asian origin and have a strong family history of type 2 diabetes. If I develop type 2 diabetes in the future and require treatment escalation to a GLP-1 agonist, I will most likely opt for a weekly injectable, as it would best fit my lifestyle. But having choices of preparation has been a huge advantage in helping my patients best individualize their therapies.
I attended the recent American Diabetes Association congress in San Diego, which had two interesting oral GLP-1 agonist sessions on the program.
The first discussed the efficacy and safety of a new daily oral nonpeptide GLP-1 agonist, orforglipron, for weight reduction in adults with obesity. The phase 2 results were impressive, with clinically significant reductions in weight and cardiometabolic parameters, and a reassuring safety profile similar to that of the injectable GLP-1 agonists.
Notably, because orforglipron is a nonpeptide, it can be taken without any food, water, or medication restrictions. This indeed could turn out to be a real game changer by simplifying the complex administration of oral semaglutide, which no doubt has hampered compliance.
In fact, an Association of British Clinical Diabetologists real-world audit (also presented at the ADA Congress as a poster) of oral semaglutide use for type 2 diabetes found clinically significant hemoglobin A1c and weight reductions, but perhaps less than expected when compared with the clinical trial program, which could be a sign of poor adherence.
A phase 3 trial of orforglipron is underway (ATTAIN-2), exploring its efficacy and safety in adults with obesity or overweight and type 2 diabetes, but it is not due to be completed until 2027.
I also attended the session presenting the results of the OASIS 1 and PIONEER-PLUS trials of higher-dose oral semaglutide.
OASIS 1 explored the efficacy and safety of high-dose oral semaglutide, 50 mg once daily, for the treatment of adults with overweight or obesity without type 2 diabetes. The investigators found clinically significant reductions in body weight of around 15%-17% from baseline, compared with placebo. This result was similar to the weight loss observed in the STEP 1 trial of 2.4 mg weekly subcutaneous injectable semaglutide in adults with obesity (a much lower dose is needed when GLP-1 agonists are given as injectables because the oral forms are not very bioavailable). The side-effect profile was also similar.
PIONEER PLUS explored the efficacy and safety of high-dose oral semaglutide 25 mg and 50 mg in adults with inadequately controlled type 2 diabetes. Patients treated with 50 mg oral semaglutide had around a 2% reduction in A1c and an 8-kg (18-lb) reduction in weight from baseline. It is well known that people with obesity and type 2 diabetes lose less weight than those with obesity alone, so this result was impressive. Again, the safety profile was similar to that of the wider class, with predictably high levels of gastrointestinal side effects.
I hope that future developments bring the class to an even wider demographic and perhaps reduce some of the global inequities in managing type 2 diabetes and obesity. It should be easier (and cheaper) to mass-produce and distribute an oral medication, compared with an injectable one.
However, it should be noted that, in the United Kingdom, the National Health Service tariff cost of oral semaglutide (at usual doses for type 2 diabetes) remains similar to that of injectable semaglutide (at doses for type 2 diabetes rather than obesity). And notably, the U.K. National Institute for Health and Care Excellence, which decides whether new drugs will be funded on the NHS, has recently delayed its decision on approving tirzepatide, a dual GLP-1 and GIP agonist, for type 2 diabetes, citing the requirement for further evidence for its clinical and cost-effectiveness. This is not uncommon for NICE, and I fully expect tirzepatide to gain NICE approval on resubmission later in 2023.
One solution to contain costs might be a phased approach to the management of obesity, with initial stages using highly efficacious obesity drugs such as tirzepatide, injectable semaglutide, or high-dose oral semaglutide, and then transitioning to lower-efficacy and cheaper obesity drugs for weight maintenance.
On this note, a generic version of liraglutide (a once-daily injectable GLP-1 agonist) will be available during 2024. Moreover, it will be interesting to see the cost of orforglipron, assuming that it is approved, when it becomes commercially available in a few years, given that a nonpeptide agent should be cheaper to produce than a peptide-like semaglutide.
This phased approach is analogous to the treatment of rheumatoid arthritis, where potent targeted biologic therapy is often used early on to achieve remission of rheumatoid arthritis, followed by a switch to a conventional disease-modifying antirheumatic drug for maintenance therapy, for reasons of long-term safety and health economics.
Using this approach for obesity management might help the sustainability of health care systems.
Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk.
A version of this article first appeared on Medscape.com.
The advent of subcutaneously injectable glucagonlike peptide–1 (GLP-1) receptor agonists for the management of type 2 diabetes during 2005 was arguably one of the greatest therapeutic advances for the condition since metformin.
I was an early advocate of the class, given its potent glucose-lowering efficacy, secondary benefits of significant weight reduction, and a low risk for hypoglycemia (if not used alongside sulfonylureas or insulin).
During 2016, the first cardiovascular outcomes trial for a GLP-1 agonist, in the form of the LEADER study, was reported. These trials were mandated by the Food and Drug Administration in the aftermath of the rosiglitazone debacle in which the type 2 diabetes drug had its use restricted because of cardiovascular events attributed to it in a meta-analysis. These events weren’t seen in a subsequent trial, and the FDA’s restrictions were later lifted.
LEADER examined the once-daily GLP-1 agonist liraglutide and showed that, in addition to its glucose-lowering effects, liraglutide brought cardiovascular benefits to the table. Moreover, during 2019, the REWIND trial, the cardiovascular outcome trial for once-weekly subcutaneous dulaglutide, revealed the same cardiovascular benefits but also demonstrated a lower incidence of macroalbuminuria, albeit with no significant improvements in hard renal endpoints such as estimated glomerular filtration decline or rates of dialysis.
Despite these compelling benefits, the uptake of GLP-1 agonists has always been slower than that of other compelling agents such as the sodium-glucose cotransporter 2 inhibitors, mainly because the latter are oral drugs, while GLP-1 agonists were initially injectable medications. This difference has proven to be a barrier for patients and clinicians alike.
However, in 2019, oral semaglutide, in doses of 7 mg and 14 mg, was approved by the FDA as the first (and still only) commercially available oral GLP-1 agonist to improve glycemic control in adults with type 2 diabetes. This approval was hailed as a “game changer” at the time. The treatment had no proven cardiovascular benefits, only lack of cardiovascular harm in PIONEER 6. The SOUL cardiovascular outcome trial for oral semaglutide in doses of 7 mg and 14 mg is due to be completed during 2024. But semaglutide certainly had compelling glucose-lowering efficacy and secondary benefits of significant weight loss similar to those of its injectable counterparts.
Cardiovascular benefits of injectable semaglutide for type 2 diabetes were demonstrated in the SUSTAIN-6 trial in 2016, and the U.S. label for Ozempic was amended accordingly in 2020.
Again, I was an early adopter of oral semaglutide, and it has been great for my patients with type 2 diabetes to have the option of a noninjectable GLP-1 agonist. However, it is not without its drawbacks: Oral semaglutide must be taken on an empty stomach, at least 30 minutes before any other food, drink, or medication, and with no more than 120 mL water to maximize absorption and bioavailability.
I am of South Asian origin and have a strong family history of type 2 diabetes. If I develop type 2 diabetes in the future and require treatment escalation to a GLP-1 agonist, I will most likely opt for a weekly injectable, as it would best fit my lifestyle. But having choices of preparation has been a huge advantage in helping my patients best individualize their therapies.
I attended the recent American Diabetes Association congress in San Diego, which had two interesting oral GLP-1 agonist sessions on the program.
The first discussed the efficacy and safety of a new daily oral nonpeptide GLP-1 agonist, orforglipron, for weight reduction in adults with obesity. The phase 2 results were impressive, with clinically significant reductions in weight and cardiometabolic parameters, and a reassuring safety profile similar to that of the injectable GLP-1 agonists.
Notably, because orforglipron is a nonpeptide, it can be taken without any food, water, or medication restrictions. This indeed could turn out to be a real game changer by simplifying the complex administration of oral semaglutide, which no doubt has hampered compliance.
In fact, an Association of British Clinical Diabetologists real-world audit (also presented at the ADA Congress as a poster) of oral semaglutide use for type 2 diabetes found clinically significant hemoglobin A1c and weight reductions, but perhaps less than expected when compared with the clinical trial program, which could be a sign of poor adherence.
A phase 3 trial of orforglipron is underway (ATTAIN-2), exploring its efficacy and safety in adults with obesity or overweight and type 2 diabetes, but it is not due to be completed until 2027.
I also attended the session presenting the results of the OASIS 1 and PIONEER-PLUS trials of higher-dose oral semaglutide.
OASIS 1 explored the efficacy and safety of high-dose oral semaglutide, 50 mg once daily, for the treatment of adults with overweight or obesity without type 2 diabetes. The investigators found clinically significant reductions in body weight of around 15%-17% from baseline, compared with placebo. This result was similar to the weight loss observed in the STEP 1 trial of 2.4 mg weekly subcutaneous injectable semaglutide in adults with obesity (a much lower dose is needed when GLP-1 agonists are given as injectables because the oral forms are not very bioavailable). The side-effect profile was also similar.
PIONEER PLUS explored the efficacy and safety of high-dose oral semaglutide 25 mg and 50 mg in adults with inadequately controlled type 2 diabetes. Patients treated with 50 mg oral semaglutide had around a 2% reduction in A1c and an 8-kg (18-lb) reduction in weight from baseline. It is well known that people with obesity and type 2 diabetes lose less weight than those with obesity alone, so this result was impressive. Again, the safety profile was similar to that of the wider class, with predictably high levels of gastrointestinal side effects.
I hope that future developments bring the class to an even wider demographic and perhaps reduce some of the global inequities in managing type 2 diabetes and obesity. It should be easier (and cheaper) to mass-produce and distribute an oral medication, compared with an injectable one.
However, it should be noted that, in the United Kingdom, the National Health Service tariff cost of oral semaglutide (at usual doses for type 2 diabetes) remains similar to that of injectable semaglutide (at doses for type 2 diabetes rather than obesity). And notably, the U.K. National Institute for Health and Care Excellence, which decides whether new drugs will be funded on the NHS, has recently delayed its decision on approving tirzepatide, a dual GLP-1 and GIP agonist, for type 2 diabetes, citing the requirement for further evidence for its clinical and cost-effectiveness. This is not uncommon for NICE, and I fully expect tirzepatide to gain NICE approval on resubmission later in 2023.
One solution to contain costs might be a phased approach to the management of obesity, with initial stages using highly efficacious obesity drugs such as tirzepatide, injectable semaglutide, or high-dose oral semaglutide, and then transitioning to lower-efficacy and cheaper obesity drugs for weight maintenance.
On this note, a generic version of liraglutide (a once-daily injectable GLP-1 agonist) will be available during 2024. Moreover, it will be interesting to see the cost of orforglipron, assuming that it is approved, when it becomes commercially available in a few years, given that a nonpeptide agent should be cheaper to produce than a peptide-like semaglutide.
This phased approach is analogous to the treatment of rheumatoid arthritis, where potent targeted biologic therapy is often used early on to achieve remission of rheumatoid arthritis, followed by a switch to a conventional disease-modifying antirheumatic drug for maintenance therapy, for reasons of long-term safety and health economics.
Using this approach for obesity management might help the sustainability of health care systems.
Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk.
A version of this article first appeared on Medscape.com.
The advent of subcutaneously injectable glucagonlike peptide–1 (GLP-1) receptor agonists for the management of type 2 diabetes during 2005 was arguably one of the greatest therapeutic advances for the condition since metformin.
I was an early advocate of the class, given its potent glucose-lowering efficacy, secondary benefits of significant weight reduction, and a low risk for hypoglycemia (if not used alongside sulfonylureas or insulin).
During 2016, the first cardiovascular outcomes trial for a GLP-1 agonist, in the form of the LEADER study, was reported. These trials were mandated by the Food and Drug Administration in the aftermath of the rosiglitazone debacle in which the type 2 diabetes drug had its use restricted because of cardiovascular events attributed to it in a meta-analysis. These events weren’t seen in a subsequent trial, and the FDA’s restrictions were later lifted.
LEADER examined the once-daily GLP-1 agonist liraglutide and showed that, in addition to its glucose-lowering effects, liraglutide brought cardiovascular benefits to the table. Moreover, during 2019, the REWIND trial, the cardiovascular outcome trial for once-weekly subcutaneous dulaglutide, revealed the same cardiovascular benefits but also demonstrated a lower incidence of macroalbuminuria, albeit with no significant improvements in hard renal endpoints such as estimated glomerular filtration decline or rates of dialysis.
Despite these compelling benefits, the uptake of GLP-1 agonists has always been slower than that of other compelling agents such as the sodium-glucose cotransporter 2 inhibitors, mainly because the latter are oral drugs, while GLP-1 agonists were initially injectable medications. This difference has proven to be a barrier for patients and clinicians alike.
However, in 2019, oral semaglutide, in doses of 7 mg and 14 mg, was approved by the FDA as the first (and still only) commercially available oral GLP-1 agonist to improve glycemic control in adults with type 2 diabetes. This approval was hailed as a “game changer” at the time. The treatment had no proven cardiovascular benefits, only lack of cardiovascular harm in PIONEER 6. The SOUL cardiovascular outcome trial for oral semaglutide in doses of 7 mg and 14 mg is due to be completed during 2024. But semaglutide certainly had compelling glucose-lowering efficacy and secondary benefits of significant weight loss similar to those of its injectable counterparts.
Cardiovascular benefits of injectable semaglutide for type 2 diabetes were demonstrated in the SUSTAIN-6 trial in 2016, and the U.S. label for Ozempic was amended accordingly in 2020.
Again, I was an early adopter of oral semaglutide, and it has been great for my patients with type 2 diabetes to have the option of a noninjectable GLP-1 agonist. However, it is not without its drawbacks: Oral semaglutide must be taken on an empty stomach, at least 30 minutes before any other food, drink, or medication, and with no more than 120 mL water to maximize absorption and bioavailability.
I am of South Asian origin and have a strong family history of type 2 diabetes. If I develop type 2 diabetes in the future and require treatment escalation to a GLP-1 agonist, I will most likely opt for a weekly injectable, as it would best fit my lifestyle. But having choices of preparation has been a huge advantage in helping my patients best individualize their therapies.
I attended the recent American Diabetes Association congress in San Diego, which had two interesting oral GLP-1 agonist sessions on the program.
The first discussed the efficacy and safety of a new daily oral nonpeptide GLP-1 agonist, orforglipron, for weight reduction in adults with obesity. The phase 2 results were impressive, with clinically significant reductions in weight and cardiometabolic parameters, and a reassuring safety profile similar to that of the injectable GLP-1 agonists.
Notably, because orforglipron is a nonpeptide, it can be taken without any food, water, or medication restrictions. This indeed could turn out to be a real game changer by simplifying the complex administration of oral semaglutide, which no doubt has hampered compliance.
In fact, an Association of British Clinical Diabetologists real-world audit (also presented at the ADA Congress as a poster) of oral semaglutide use for type 2 diabetes found clinically significant hemoglobin A1c and weight reductions, but perhaps less than expected when compared with the clinical trial program, which could be a sign of poor adherence.
A phase 3 trial of orforglipron is underway (ATTAIN-2), exploring its efficacy and safety in adults with obesity or overweight and type 2 diabetes, but it is not due to be completed until 2027.
I also attended the session presenting the results of the OASIS 1 and PIONEER-PLUS trials of higher-dose oral semaglutide.
OASIS 1 explored the efficacy and safety of high-dose oral semaglutide, 50 mg once daily, for the treatment of adults with overweight or obesity without type 2 diabetes. The investigators found clinically significant reductions in body weight of around 15%-17% from baseline, compared with placebo. This result was similar to the weight loss observed in the STEP 1 trial of 2.4 mg weekly subcutaneous injectable semaglutide in adults with obesity (a much lower dose is needed when GLP-1 agonists are given as injectables because the oral forms are not very bioavailable). The side-effect profile was also similar.
PIONEER PLUS explored the efficacy and safety of high-dose oral semaglutide 25 mg and 50 mg in adults with inadequately controlled type 2 diabetes. Patients treated with 50 mg oral semaglutide had around a 2% reduction in A1c and an 8-kg (18-lb) reduction in weight from baseline. It is well known that people with obesity and type 2 diabetes lose less weight than those with obesity alone, so this result was impressive. Again, the safety profile was similar to that of the wider class, with predictably high levels of gastrointestinal side effects.
I hope that future developments bring the class to an even wider demographic and perhaps reduce some of the global inequities in managing type 2 diabetes and obesity. It should be easier (and cheaper) to mass-produce and distribute an oral medication, compared with an injectable one.
However, it should be noted that, in the United Kingdom, the National Health Service tariff cost of oral semaglutide (at usual doses for type 2 diabetes) remains similar to that of injectable semaglutide (at doses for type 2 diabetes rather than obesity). And notably, the U.K. National Institute for Health and Care Excellence, which decides whether new drugs will be funded on the NHS, has recently delayed its decision on approving tirzepatide, a dual GLP-1 and GIP agonist, for type 2 diabetes, citing the requirement for further evidence for its clinical and cost-effectiveness. This is not uncommon for NICE, and I fully expect tirzepatide to gain NICE approval on resubmission later in 2023.
One solution to contain costs might be a phased approach to the management of obesity, with initial stages using highly efficacious obesity drugs such as tirzepatide, injectable semaglutide, or high-dose oral semaglutide, and then transitioning to lower-efficacy and cheaper obesity drugs for weight maintenance.
On this note, a generic version of liraglutide (a once-daily injectable GLP-1 agonist) will be available during 2024. Moreover, it will be interesting to see the cost of orforglipron, assuming that it is approved, when it becomes commercially available in a few years, given that a nonpeptide agent should be cheaper to produce than a peptide-like semaglutide.
This phased approach is analogous to the treatment of rheumatoid arthritis, where potent targeted biologic therapy is often used early on to achieve remission of rheumatoid arthritis, followed by a switch to a conventional disease-modifying antirheumatic drug for maintenance therapy, for reasons of long-term safety and health economics.
Using this approach for obesity management might help the sustainability of health care systems.
Dr. Fernando is a general practitioner near Edinburgh. He reported receiving speaker fees from Eli Lilly and Novo Nordisk.
A version of this article first appeared on Medscape.com.
In-office infusions at risk with new Medicare Part B reimbursement recommendation
The Medicare Payment Advisory Commission (MedPAC) is an independent agency to advise Congress on Medicare (MC) policy, much of which pertains to payment issues. The 17 commissioners meet publicly and issue two reports a year with their recommendations to Congress, who then decides whether to enact these recommendations or not.
One MedPAC recommendation in 2023 was quickly introduced in the House of Representatives in May and passed the Energy and Commerce Committee 49-0. That recommendation relates to “site neutrality” payments to MC providers. If passed by Congress, it would result in some “site-neutral” cuts to hospitals. That MedPAC recommendation was acted upon very quickly by Congress. Consequently, it is important to discuss the potential negative ramifications of other MedPAC recommendations released in June regarding reimbursement of Medicare Part B drugs and proactively educate Congress accordingly on those ramifications.
Medicare Part B drugs
Medicare Part B drugs are those administered by providers, unlike the Part D medications which are generally obtained through pharmacies. Presently, MC reimburses providers for the administered Part B medication based on the average sales price (ASP) plus 6%. However, with sequestration, that add-on amount is reduced to ASP plus 4.3%. It has long been touted by MedPAC and other policy makers that physicians choose to infuse higher-priced drugs in order to increase reimbursements. That has not been borne out when it comes to rheumatologists, and, in fact, a retired MedPAC commissioner even stated that premise did not hold true for rheumatologists.
Regardless, it continues to be suggested that MC should reduce its costs for Part B medications by reducing reimbursement to physicians. It should be noted that often the margins on the drugs are already quite thin, and at times the reimbursement amount, compared with the acquisition cost of the drug even leaves the physician “underwater.”
A few years ago, there was a proposed Part B demonstration project that essentially removed the +6% add-on and replaced it with a very low fixed amount that would have left most physicians “underwater” in their Part B drug acquisitions. This was vigorously opposed by physicians around the country, who let Congress know exactly how they felt. We have been told that the Coalition of State Rheumatology Organizations was one of the most vociferous organizations that helped in fighting back this proposal and resulting in its withdrawal.
MedPAC recommendations
That brings us back to MedPAC. In June, MedPAC released recommendations to Congress in an attempt to address the “high price of drugs” covered under MC Part B. Unfortunately, the recommendations do nothing to address the root cause of high drug prices, but once again attempt to balance MC expenditures on the backs of physicians. In this case, it is physicians who infuse Part B drugs in their office to chronically ill patients. In-office infusions have been shown to be the most cost-effective site of care, as well as being safer when compared with home infusion for a number of rheumatologic medications.
One of the MedPAC recommendations gives the Secretary of Health & Human Services the authority to establish a single ASP for drugs with “similar health effects.” The ambiguity of the phrase “similar health effects” should put us all on alert as to the significant unintended consequences that may result. For example, HHS could assign one ASP to all drugs that treat rheumatoid arthritis based on the lowest ASP of the group. This certainly would lead to a number of drugs being out of reach for MC beneficiaries if the artificial ASP of the medication is much lower than the actual acquisition cost of the drug, leaving physicians unable to acquire it. Yet, MedPAC states this recommendation would not affect access to care for MC beneficiaries.
Another recommendation would require HHS to reduce or eliminate the add-on percentage to the ASP for higher-priced drugs and/or put in an added fixed amount. This recommendation is clearly reminiscent of the old ill-conceived Part B demonstration project.
A fixed “add-on amount” might work if it is sufficient to cover the overhead of maintaining a provider’s infusion suite. But if practices are left underwater in their purchases of certain Part B drugs, there may be no choice but to stop offering those infusions to MC beneficiaries or – worst-case scenario – shut the door completely. Yet again, MedPAC stated that this recommendation would not result in a loss of access to these treatments for MC beneficiaries.
Loss of access?
Rheumatologists have gone to great lengths to continue offering care to MC patients in spite of the yearly cuts and threats of more cuts in the future to physician reimbursements. In addition, physicians have no annual inflationary update to their reimbursements. I am not sure how MedPAC concludes that continued cuts to physician fee schedules, along with a decrease in reimbursement for administered drugs, will not affect access to care for MC beneficiaries.
Finally, the timing on these recommendations is confusing, considering that implementation of the Inflation Reduction Act (IRA) has just begun. Next quarter, a number of Part B drugs will be subject to inflationary penalties; there will also be additional Part B biosimilars coming to market, resulting in lower ASPs. And don’t forget, the IRA just instituted an ASP plus 8% reimbursement for biosimilars in an attempt to get physicians to do something that the Centers for Medicare & Medicaid Services has asked them not to do. That is, choose a drug based on its reimbursement, not necessarily the one which is right for the patient.
Overall, with so many variables up in the air, now is not the time to create even more uncertainty for physicians and the Medicare patients that they take care of.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at rhnews@mdedge.com.
The Medicare Payment Advisory Commission (MedPAC) is an independent agency to advise Congress on Medicare (MC) policy, much of which pertains to payment issues. The 17 commissioners meet publicly and issue two reports a year with their recommendations to Congress, who then decides whether to enact these recommendations or not.
One MedPAC recommendation in 2023 was quickly introduced in the House of Representatives in May and passed the Energy and Commerce Committee 49-0. That recommendation relates to “site neutrality” payments to MC providers. If passed by Congress, it would result in some “site-neutral” cuts to hospitals. That MedPAC recommendation was acted upon very quickly by Congress. Consequently, it is important to discuss the potential negative ramifications of other MedPAC recommendations released in June regarding reimbursement of Medicare Part B drugs and proactively educate Congress accordingly on those ramifications.
Medicare Part B drugs
Medicare Part B drugs are those administered by providers, unlike the Part D medications which are generally obtained through pharmacies. Presently, MC reimburses providers for the administered Part B medication based on the average sales price (ASP) plus 6%. However, with sequestration, that add-on amount is reduced to ASP plus 4.3%. It has long been touted by MedPAC and other policy makers that physicians choose to infuse higher-priced drugs in order to increase reimbursements. That has not been borne out when it comes to rheumatologists, and, in fact, a retired MedPAC commissioner even stated that premise did not hold true for rheumatologists.
Regardless, it continues to be suggested that MC should reduce its costs for Part B medications by reducing reimbursement to physicians. It should be noted that often the margins on the drugs are already quite thin, and at times the reimbursement amount, compared with the acquisition cost of the drug even leaves the physician “underwater.”
A few years ago, there was a proposed Part B demonstration project that essentially removed the +6% add-on and replaced it with a very low fixed amount that would have left most physicians “underwater” in their Part B drug acquisitions. This was vigorously opposed by physicians around the country, who let Congress know exactly how they felt. We have been told that the Coalition of State Rheumatology Organizations was one of the most vociferous organizations that helped in fighting back this proposal and resulting in its withdrawal.
MedPAC recommendations
That brings us back to MedPAC. In June, MedPAC released recommendations to Congress in an attempt to address the “high price of drugs” covered under MC Part B. Unfortunately, the recommendations do nothing to address the root cause of high drug prices, but once again attempt to balance MC expenditures on the backs of physicians. In this case, it is physicians who infuse Part B drugs in their office to chronically ill patients. In-office infusions have been shown to be the most cost-effective site of care, as well as being safer when compared with home infusion for a number of rheumatologic medications.
One of the MedPAC recommendations gives the Secretary of Health & Human Services the authority to establish a single ASP for drugs with “similar health effects.” The ambiguity of the phrase “similar health effects” should put us all on alert as to the significant unintended consequences that may result. For example, HHS could assign one ASP to all drugs that treat rheumatoid arthritis based on the lowest ASP of the group. This certainly would lead to a number of drugs being out of reach for MC beneficiaries if the artificial ASP of the medication is much lower than the actual acquisition cost of the drug, leaving physicians unable to acquire it. Yet, MedPAC states this recommendation would not affect access to care for MC beneficiaries.
Another recommendation would require HHS to reduce or eliminate the add-on percentage to the ASP for higher-priced drugs and/or put in an added fixed amount. This recommendation is clearly reminiscent of the old ill-conceived Part B demonstration project.
A fixed “add-on amount” might work if it is sufficient to cover the overhead of maintaining a provider’s infusion suite. But if practices are left underwater in their purchases of certain Part B drugs, there may be no choice but to stop offering those infusions to MC beneficiaries or – worst-case scenario – shut the door completely. Yet again, MedPAC stated that this recommendation would not result in a loss of access to these treatments for MC beneficiaries.
Loss of access?
Rheumatologists have gone to great lengths to continue offering care to MC patients in spite of the yearly cuts and threats of more cuts in the future to physician reimbursements. In addition, physicians have no annual inflationary update to their reimbursements. I am not sure how MedPAC concludes that continued cuts to physician fee schedules, along with a decrease in reimbursement for administered drugs, will not affect access to care for MC beneficiaries.
Finally, the timing on these recommendations is confusing, considering that implementation of the Inflation Reduction Act (IRA) has just begun. Next quarter, a number of Part B drugs will be subject to inflationary penalties; there will also be additional Part B biosimilars coming to market, resulting in lower ASPs. And don’t forget, the IRA just instituted an ASP plus 8% reimbursement for biosimilars in an attempt to get physicians to do something that the Centers for Medicare & Medicaid Services has asked them not to do. That is, choose a drug based on its reimbursement, not necessarily the one which is right for the patient.
Overall, with so many variables up in the air, now is not the time to create even more uncertainty for physicians and the Medicare patients that they take care of.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at rhnews@mdedge.com.
The Medicare Payment Advisory Commission (MedPAC) is an independent agency to advise Congress on Medicare (MC) policy, much of which pertains to payment issues. The 17 commissioners meet publicly and issue two reports a year with their recommendations to Congress, who then decides whether to enact these recommendations or not.
One MedPAC recommendation in 2023 was quickly introduced in the House of Representatives in May and passed the Energy and Commerce Committee 49-0. That recommendation relates to “site neutrality” payments to MC providers. If passed by Congress, it would result in some “site-neutral” cuts to hospitals. That MedPAC recommendation was acted upon very quickly by Congress. Consequently, it is important to discuss the potential negative ramifications of other MedPAC recommendations released in June regarding reimbursement of Medicare Part B drugs and proactively educate Congress accordingly on those ramifications.
Medicare Part B drugs
Medicare Part B drugs are those administered by providers, unlike the Part D medications which are generally obtained through pharmacies. Presently, MC reimburses providers for the administered Part B medication based on the average sales price (ASP) plus 6%. However, with sequestration, that add-on amount is reduced to ASP plus 4.3%. It has long been touted by MedPAC and other policy makers that physicians choose to infuse higher-priced drugs in order to increase reimbursements. That has not been borne out when it comes to rheumatologists, and, in fact, a retired MedPAC commissioner even stated that premise did not hold true for rheumatologists.
Regardless, it continues to be suggested that MC should reduce its costs for Part B medications by reducing reimbursement to physicians. It should be noted that often the margins on the drugs are already quite thin, and at times the reimbursement amount, compared with the acquisition cost of the drug even leaves the physician “underwater.”
A few years ago, there was a proposed Part B demonstration project that essentially removed the +6% add-on and replaced it with a very low fixed amount that would have left most physicians “underwater” in their Part B drug acquisitions. This was vigorously opposed by physicians around the country, who let Congress know exactly how they felt. We have been told that the Coalition of State Rheumatology Organizations was one of the most vociferous organizations that helped in fighting back this proposal and resulting in its withdrawal.
MedPAC recommendations
That brings us back to MedPAC. In June, MedPAC released recommendations to Congress in an attempt to address the “high price of drugs” covered under MC Part B. Unfortunately, the recommendations do nothing to address the root cause of high drug prices, but once again attempt to balance MC expenditures on the backs of physicians. In this case, it is physicians who infuse Part B drugs in their office to chronically ill patients. In-office infusions have been shown to be the most cost-effective site of care, as well as being safer when compared with home infusion for a number of rheumatologic medications.
One of the MedPAC recommendations gives the Secretary of Health & Human Services the authority to establish a single ASP for drugs with “similar health effects.” The ambiguity of the phrase “similar health effects” should put us all on alert as to the significant unintended consequences that may result. For example, HHS could assign one ASP to all drugs that treat rheumatoid arthritis based on the lowest ASP of the group. This certainly would lead to a number of drugs being out of reach for MC beneficiaries if the artificial ASP of the medication is much lower than the actual acquisition cost of the drug, leaving physicians unable to acquire it. Yet, MedPAC states this recommendation would not affect access to care for MC beneficiaries.
Another recommendation would require HHS to reduce or eliminate the add-on percentage to the ASP for higher-priced drugs and/or put in an added fixed amount. This recommendation is clearly reminiscent of the old ill-conceived Part B demonstration project.
A fixed “add-on amount” might work if it is sufficient to cover the overhead of maintaining a provider’s infusion suite. But if practices are left underwater in their purchases of certain Part B drugs, there may be no choice but to stop offering those infusions to MC beneficiaries or – worst-case scenario – shut the door completely. Yet again, MedPAC stated that this recommendation would not result in a loss of access to these treatments for MC beneficiaries.
Loss of access?
Rheumatologists have gone to great lengths to continue offering care to MC patients in spite of the yearly cuts and threats of more cuts in the future to physician reimbursements. In addition, physicians have no annual inflationary update to their reimbursements. I am not sure how MedPAC concludes that continued cuts to physician fee schedules, along with a decrease in reimbursement for administered drugs, will not affect access to care for MC beneficiaries.
Finally, the timing on these recommendations is confusing, considering that implementation of the Inflation Reduction Act (IRA) has just begun. Next quarter, a number of Part B drugs will be subject to inflationary penalties; there will also be additional Part B biosimilars coming to market, resulting in lower ASPs. And don’t forget, the IRA just instituted an ASP plus 8% reimbursement for biosimilars in an attempt to get physicians to do something that the Centers for Medicare & Medicaid Services has asked them not to do. That is, choose a drug based on its reimbursement, not necessarily the one which is right for the patient.
Overall, with so many variables up in the air, now is not the time to create even more uncertainty for physicians and the Medicare patients that they take care of.
Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s Vice President of Advocacy and Government Affairs and its immediate Past President, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at rhnews@mdedge.com.
Dangerous grandparents
Many decades ago I wrote a book I brazenly titled: “The Good Grandmother Handbook.” I had been a parent for a scant 7 or 8 years but based on my experiences in the office I felt I had accumulated enough wisdom to suggest to women in their fifth to seventh decades how they might conduct themselves around their grandchildren. Luckily, the book never got further than several hundred pages of crudely typed manuscript. This was before word processing programs had settled into the home computer industry, which was still in its infancy.
But I continue find the subject of grandparents interesting. Now, with grandchildren of my own (the oldest has just graduated from high school) and scores of peers knee deep in their own grandparenting adventures, I hope that my perspective now has a bit less of a holier-than-thou aroma.
My most recent muse-prodding event came when I stumbled across an article about the epidemiology of unintentional pediatric firearm fatalities. Looking at 10 years of data from the National Violent Death Reporting System, the investigators found that in 80% of the cases the firearm owner was a relative of the victim; in slightly more than 60% of the cases the event occurred in the victim’s home.
The data set was not granular enough to define the exact relationship between the child and relative who owned the gun. I suspect that most often the relative was a parent or an uncle or aunt. However, viewed through my septuagenarian prism, this paper prompted me to wonder in how many of these fatalities the firearm owner was a grandparent.
I have only anecdotal observations, but I can easily recall situations here in Maine in which a child has been injured by his or her grandfather’s gun. The data from the study show that pediatric fatalities are bimodal, with the majority occurring in the 1- to 5-year age group and a second peak in adolescence. The grandparent-involved cases I can recall were in the younger demographic.
Unfortunately, firearms aren’t the only threat that other grandparents and I pose to the health and safety of our grandchildren. I can remember before the development of, and the widespread use of, tamper-proof pill bottles, “grandma’s purse” overdoses were an unfortunately common occurrence.
More recently, at least here in Maine, we have been hearing more about motorized vehicle–related injuries and fatalities – grandparents backing over their grandchildren in the driveway or, more often, grandfathers (usually) taking their young grandchildren for rides on their snowmobiles, ATVs, lawn tractors, (fill in the blank). Whenever one of these events occurs, my mind quickly jumps beyond the tragic loss of life to imagining what terrible and long-lasting emotional chaos these incidents have spawned in those families.
During the pandemic, many parents and grandparents became aware of the threat that viral-spewing young children pose to the older and more vulnerable generation. On the other hand, many parents have been told that having a grandparent around can present a risk to the health and safety of their grandchildren. It can be a touchy subject in families, and grandparents may bristle at “being treated like a child” when they are reminded that children aren’t small adults and that their own behavior may be setting a bad example or putting their grandchildren at risk.
My generation had to learn how to buckle infants and toddlers into car seats because it was something that wasn’t done for our children. Fortunately, most new grandparents now already have those buckle-and-click skills and mindset. But,
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Many decades ago I wrote a book I brazenly titled: “The Good Grandmother Handbook.” I had been a parent for a scant 7 or 8 years but based on my experiences in the office I felt I had accumulated enough wisdom to suggest to women in their fifth to seventh decades how they might conduct themselves around their grandchildren. Luckily, the book never got further than several hundred pages of crudely typed manuscript. This was before word processing programs had settled into the home computer industry, which was still in its infancy.
But I continue find the subject of grandparents interesting. Now, with grandchildren of my own (the oldest has just graduated from high school) and scores of peers knee deep in their own grandparenting adventures, I hope that my perspective now has a bit less of a holier-than-thou aroma.
My most recent muse-prodding event came when I stumbled across an article about the epidemiology of unintentional pediatric firearm fatalities. Looking at 10 years of data from the National Violent Death Reporting System, the investigators found that in 80% of the cases the firearm owner was a relative of the victim; in slightly more than 60% of the cases the event occurred in the victim’s home.
The data set was not granular enough to define the exact relationship between the child and relative who owned the gun. I suspect that most often the relative was a parent or an uncle or aunt. However, viewed through my septuagenarian prism, this paper prompted me to wonder in how many of these fatalities the firearm owner was a grandparent.
I have only anecdotal observations, but I can easily recall situations here in Maine in which a child has been injured by his or her grandfather’s gun. The data from the study show that pediatric fatalities are bimodal, with the majority occurring in the 1- to 5-year age group and a second peak in adolescence. The grandparent-involved cases I can recall were in the younger demographic.
Unfortunately, firearms aren’t the only threat that other grandparents and I pose to the health and safety of our grandchildren. I can remember before the development of, and the widespread use of, tamper-proof pill bottles, “grandma’s purse” overdoses were an unfortunately common occurrence.
More recently, at least here in Maine, we have been hearing more about motorized vehicle–related injuries and fatalities – grandparents backing over their grandchildren in the driveway or, more often, grandfathers (usually) taking their young grandchildren for rides on their snowmobiles, ATVs, lawn tractors, (fill in the blank). Whenever one of these events occurs, my mind quickly jumps beyond the tragic loss of life to imagining what terrible and long-lasting emotional chaos these incidents have spawned in those families.
During the pandemic, many parents and grandparents became aware of the threat that viral-spewing young children pose to the older and more vulnerable generation. On the other hand, many parents have been told that having a grandparent around can present a risk to the health and safety of their grandchildren. It can be a touchy subject in families, and grandparents may bristle at “being treated like a child” when they are reminded that children aren’t small adults and that their own behavior may be setting a bad example or putting their grandchildren at risk.
My generation had to learn how to buckle infants and toddlers into car seats because it was something that wasn’t done for our children. Fortunately, most new grandparents now already have those buckle-and-click skills and mindset. But,
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Many decades ago I wrote a book I brazenly titled: “The Good Grandmother Handbook.” I had been a parent for a scant 7 or 8 years but based on my experiences in the office I felt I had accumulated enough wisdom to suggest to women in their fifth to seventh decades how they might conduct themselves around their grandchildren. Luckily, the book never got further than several hundred pages of crudely typed manuscript. This was before word processing programs had settled into the home computer industry, which was still in its infancy.
But I continue find the subject of grandparents interesting. Now, with grandchildren of my own (the oldest has just graduated from high school) and scores of peers knee deep in their own grandparenting adventures, I hope that my perspective now has a bit less of a holier-than-thou aroma.
My most recent muse-prodding event came when I stumbled across an article about the epidemiology of unintentional pediatric firearm fatalities. Looking at 10 years of data from the National Violent Death Reporting System, the investigators found that in 80% of the cases the firearm owner was a relative of the victim; in slightly more than 60% of the cases the event occurred in the victim’s home.
The data set was not granular enough to define the exact relationship between the child and relative who owned the gun. I suspect that most often the relative was a parent or an uncle or aunt. However, viewed through my septuagenarian prism, this paper prompted me to wonder in how many of these fatalities the firearm owner was a grandparent.
I have only anecdotal observations, but I can easily recall situations here in Maine in which a child has been injured by his or her grandfather’s gun. The data from the study show that pediatric fatalities are bimodal, with the majority occurring in the 1- to 5-year age group and a second peak in adolescence. The grandparent-involved cases I can recall were in the younger demographic.
Unfortunately, firearms aren’t the only threat that other grandparents and I pose to the health and safety of our grandchildren. I can remember before the development of, and the widespread use of, tamper-proof pill bottles, “grandma’s purse” overdoses were an unfortunately common occurrence.
More recently, at least here in Maine, we have been hearing more about motorized vehicle–related injuries and fatalities – grandparents backing over their grandchildren in the driveway or, more often, grandfathers (usually) taking their young grandchildren for rides on their snowmobiles, ATVs, lawn tractors, (fill in the blank). Whenever one of these events occurs, my mind quickly jumps beyond the tragic loss of life to imagining what terrible and long-lasting emotional chaos these incidents have spawned in those families.
During the pandemic, many parents and grandparents became aware of the threat that viral-spewing young children pose to the older and more vulnerable generation. On the other hand, many parents have been told that having a grandparent around can present a risk to the health and safety of their grandchildren. It can be a touchy subject in families, and grandparents may bristle at “being treated like a child” when they are reminded that children aren’t small adults and that their own behavior may be setting a bad example or putting their grandchildren at risk.
My generation had to learn how to buckle infants and toddlers into car seats because it was something that wasn’t done for our children. Fortunately, most new grandparents now already have those buckle-and-click skills and mindset. But,
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Thoughts on primary care in 2023
As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.
- Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
- Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
- Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.1 The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
- Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.2 Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.
There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.
2. Budd J. J Prim Care Community Health. 2023 Apr 19.
As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.
- Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
- Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
- Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.1 The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
- Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.2 Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.
There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.
2. Budd J. J Prim Care Community Health. 2023 Apr 19.
As we all face remarkable challenges in giving great care to our patients and maintaining great care for ourselves, I wanted to share a few thoughts I have had regarding difficult things I have seen in the past few months.
- Call centers: Yikes! I think this is an overlooked stress on the primary care system. In a cost-cutting effort, organizations have gone to call centers to handle incoming calls, and hold times can be enormous. My own organization often has wait times longer than 30 minutes. I recently called another organization and had a wait time more than 30 minutes. Patients become frustrated and will message their primary care team to intervene for scheduling issues then will arrive at their appointments frustrated by all the hassles.
- Difficult encounters: We all have visits that we know will be challenging. I think it is even more difficult when we enter the visit stressed and tired. I have always found that, when I am in a calm place, even the most difficult visits go much better. Our patients arrive at clinic visits more stressed and tired too, as they face the challenge of a stretched and overwhelmed primary care system.
- Limited availability of specialists: My organization has had a sharp increase in wait times for specialty care over the past few years. Waits for some specialties can be almost a year. A study by Reddy and colleagues found a wait time of 3 months for patients referred to gastroenterologists.1 The lack of timely access to specialists adds to the stress and burden of primary care professionals. Managing problems deemed in need of subspecialty care as patients wait for appointments is difficult.
- Patient portals: Some practices are starting to figure this out this problem, others aren’t. Budd reviewed all the factors with the EHR that contribute to physician burnout.2 Portals have added another source of patient care outside face-to-face visits that adds to physician work load; for many practices is not appropriately accounted for in effort or productivity measures. Some practices are now starting to charge for patient messaging, but this may require even more physician time in documentation and billing. Unless this directly helps the physician reduce work hours or improve compensation, then it may make the problem worse.
There is little mystery why it seems so hard ... it is! Many things have been added to the plate of primary care professionals (increased messaging, calming patients frustrated with the medical system, and increased need for bridging care while patients wait for specialty appointments). Our patients need us now more than ever to give excellent, compassionate care in a poorly functioning system. We need to be emotionally and physically healthy enough to be there for our patients. Prioritize your own needs.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Reddy K et al. Health Equity. 2018 Jun 1;2(1):103-8.
2. Budd J. J Prim Care Community Health. 2023 Apr 19.
The Growing Pains of Changing Times for Acne and Rosacea Pathophysiology: Where Will It All End Up?
It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.1 Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.2-4
If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.5 Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.6 This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.10-12
Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.13 This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.17,18
I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.
Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.19-21
There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.
- Wu J, Fang Z, Liu T, et al. Maximizing the utility of transcriptomics data in inflammatory skin diseases. Front Immunol. 2021;12:761890.
- Firlej E, Kowalska W, Szymaszek K, et al. The role of skin immune system in acne. J Clin Med. 2022;11:1579.
- Mias C, Mengeaud V, Bessou-Touya S, et al. Recent advances in understanding inflammatory acne: deciphering the relationship between Cutibacterium acnes and Th17 inflammatory pathway. J Eur Acad Dermatol Venereol. 2023;(37 suppl 2):3-11.
- Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:F1000 Faculty Rev-1885. doi:10.12688/f1000research.16537.1
- Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi:10.12688/f1000research.15659.1
- Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
- Kim J. Review of the innate immune response in acne vulgaris: activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology. 2005;211:193-198.
- Del Rosso JQ, Webster G, Weiss JS, et al. Nonantibiotic properties of tetracyclines in rosacea and their clinical implications. J Clin Aesthet Dermatol. 2021;14:14-21.
- Zhu W, Wang HL, Bu XL, et al. A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris. Ann Transl Med. 2022;10:645.
- Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Dermatol. 2014;7(2 suppl):S3-S21.
- Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, treatment, crossover study. J Am Acad Dermatol. 2013;69:762-767.
- Del Rosso JQ, Stein Gold L, Seagal J, et al. An open-label, phase IV study evaluating Lidose-isotretinoin administered without food in patients with severe recalcitrant nodular acne: low relapse rates observed over the 104-week post-treatment period. J Clin Aesthet Dermatol. 2019;12:13-18.
- Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587.
- Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:2-11.
- Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
- Tanghetti E, Del Rosso JQ, Thiboutot D, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 4: a status report on physical modalities and devices. Cutis. 2014;93:71-76.
- Del Rosso JQ, Gallo RL, Tanghetti E, et al. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis. 2013;91(3 suppl):1-8.
- Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182:1269-1276.
- Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019;20:335-344.
- Daou H, Paradiso M, Hennessy K. Rosacea and the microbiome: a systematic review. Dermatol Ther (Heidelb). 2021;11:1-12.
- Kayiran MA, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.1 Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.2-4
If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.5 Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.6 This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.10-12
Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.13 This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.17,18
I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.
Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.19-21
There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.
It is interesting to observe the changes in dermatology that have occurred over the last 1 to 2 decades, especially as major advances in basic science research techniques have rapidly expanded our current understanding of the pathophysiology of many disease states—psoriasis, psoriatic arthritis, atopic dermatitis, alopecia areata, vitiligo, hidradenitis suppurativa, and lichen planus.1 Although acne vulgaris (AV) and rosacea do not make front-page news quite as often as some of these other aforementioned disease states in the pathophysiology arena, advances still have been made in understanding the pathophysiology, albeit slower and often less popularized in dermatology publications and other forms of media.2-4
If one looks at our fundamental understanding of AV, most of the discussion over multiple decades has been driven by new treatments and in some cases new formulations and packaging differences with topical agents. Although we understood that adrenarche, a subsequent increase in androgen synthesis, and the ensuing sebocyte development with formation of sebum were prerequisites for the development of AV, the absence of therapeutic options to address these vital components of AV—especially US Food and Drug Administration (FDA)–approved therapies—resulted in limited discussion about this specific area.5 Rather, the discussion was dominated by the notable role of Propionibacterium acnes (now called Cutibacterium acnes) in AV pathophysiology, as we had therapies such as benzoyl peroxide and antibiotics that improved AV in direct correlation with reductions in P acnes.6 This was soon coupled with an advanced understanding of how to reduce follicular hyperkeratinization with the development of topical tretinoin, followed by 3 other topical retinoids over time—adapalene, tazarotene, and trifarotene. Over subsequent years, slowly emerging basic science developments and collective data reviews added to our understanding of AV and how different therapies appear to work, including the role of toll-like receptors, anti-inflammatory properties of tetracyclines, and inflammasomes.7-9 Without a doubt, the availability of oral isotretinoin revolutionized AV therapy, especially in patients with severe refractory disease, with advanced formulations allowing for optimization of sustained remission without the need for high dietary fat intake.10-12
Progress in the pathophysiology of rosacea has been slower to develop, with the first true discussion of specific clinical presentations published after the new millennium.13 This was followed by more advanced basic science and clinical research, which led to an improved ability to understand modes of action of various therapies and to correlate treatment selection with specific visible manifestations of rosacea, including incorporation of physical devices.14-16 A newer perspective on evaluation and management of rosacea moved away from the “buckets” of rosacea subtypes to phenotypes observed at the time of clinical presentation.17,18
I could elaborate on research advancements with both diseases, but the bottom line is that information, developments, and current perspectives change over time. Keeping up is a challenge for all who study and practice dermatology. It is human nature to revert to what we already believe and do, which sometimes remains valid and other times is quite outdated and truly replaced by more optimal approaches. With AV and rosacea, progress is much slower in availability of newer agents. With AV, new agents have included topical dapsone, oral sarecycline, and topical clascoterone, with the latter being the first FDA-approved topical agent to mitigate the effects of androgens and sebum in both males and females. For rosacea, the 2 most recent FDA-approved therapies are minocycline foam and microencapsulated benzoyl peroxide. All of these therapies are proven to be effective for the modes of action and skin manifestations they specifically manage. Over the upcoming year, we are hoping to see the first triple-combination topical product come to market for AV, which will prompt our minds to consider if and how 3 established agents can work together to further augment treatment efficacy with favorable tolerability and safety.
Where will all of this end up? It is hard to say. We still have several other areas to tackle with both disease states, including establishing a well-substantiated understanding of the pathophysiologic role of the microbiome, sorting out the role of antibiotic use due to concerns about bacterial resistance, integration of FDA-approved physical devices in AV, and data on both diet and optimized skin care, to name a few.19-21
There is a lot on the plate to accomplish and digest. I have remained very involved in this subject matter for almost 3 decades and am still feeling the growing pains. Fortunately, the satisfaction of being part of a process so important to the lives of millions of patients makes this worth every moment. Stay tuned—more valuable information is to come.
- Wu J, Fang Z, Liu T, et al. Maximizing the utility of transcriptomics data in inflammatory skin diseases. Front Immunol. 2021;12:761890.
- Firlej E, Kowalska W, Szymaszek K, et al. The role of skin immune system in acne. J Clin Med. 2022;11:1579.
- Mias C, Mengeaud V, Bessou-Touya S, et al. Recent advances in understanding inflammatory acne: deciphering the relationship between Cutibacterium acnes and Th17 inflammatory pathway. J Eur Acad Dermatol Venereol. 2023;(37 suppl 2):3-11.
- Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:F1000 Faculty Rev-1885. doi:10.12688/f1000research.16537.1
- Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi:10.12688/f1000research.15659.1
- Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
- Kim J. Review of the innate immune response in acne vulgaris: activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology. 2005;211:193-198.
- Del Rosso JQ, Webster G, Weiss JS, et al. Nonantibiotic properties of tetracyclines in rosacea and their clinical implications. J Clin Aesthet Dermatol. 2021;14:14-21.
- Zhu W, Wang HL, Bu XL, et al. A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris. Ann Transl Med. 2022;10:645.
- Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Dermatol. 2014;7(2 suppl):S3-S21.
- Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, treatment, crossover study. J Am Acad Dermatol. 2013;69:762-767.
- Del Rosso JQ, Stein Gold L, Seagal J, et al. An open-label, phase IV study evaluating Lidose-isotretinoin administered without food in patients with severe recalcitrant nodular acne: low relapse rates observed over the 104-week post-treatment period. J Clin Aesthet Dermatol. 2019;12:13-18.
- Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587.
- Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:2-11.
- Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
- Tanghetti E, Del Rosso JQ, Thiboutot D, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 4: a status report on physical modalities and devices. Cutis. 2014;93:71-76.
- Del Rosso JQ, Gallo RL, Tanghetti E, et al. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis. 2013;91(3 suppl):1-8.
- Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182:1269-1276.
- Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019;20:335-344.
- Daou H, Paradiso M, Hennessy K. Rosacea and the microbiome: a systematic review. Dermatol Ther (Heidelb). 2021;11:1-12.
- Kayiran MA, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
- Wu J, Fang Z, Liu T, et al. Maximizing the utility of transcriptomics data in inflammatory skin diseases. Front Immunol. 2021;12:761890.
- Firlej E, Kowalska W, Szymaszek K, et al. The role of skin immune system in acne. J Clin Med. 2022;11:1579.
- Mias C, Mengeaud V, Bessou-Touya S, et al. Recent advances in understanding inflammatory acne: deciphering the relationship between Cutibacterium acnes and Th17 inflammatory pathway. J Eur Acad Dermatol Venereol. 2023;(37 suppl 2):3-11.
- Buddenkotte J, Steinhoff M. Recent advances in understanding and managing rosacea. F1000Res. 2018;7:F1000 Faculty Rev-1885. doi:10.12688/f1000research.16537.1
- Platsidaki E, Dessinioti C. Recent advances in understanding Propionibacterium acnes (Cutibacterium acnes) in acne. F1000Res. 2018;7:F1000 Faculty Rev-1953. doi:10.12688/f1000research.15659.1
- Leyden JJ. The evolving role of Propionibacterium acnes in acne. Semin Cutan Med Surg. 2001;20:139-143.
- Kim J. Review of the innate immune response in acne vulgaris: activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology. 2005;211:193-198.
- Del Rosso JQ, Webster G, Weiss JS, et al. Nonantibiotic properties of tetracyclines in rosacea and their clinical implications. J Clin Aesthet Dermatol. 2021;14:14-21.
- Zhu W, Wang HL, Bu XL, et al. A narrative review of research progress on the role of NLRP3 inflammasome in acne vulgaris. Ann Transl Med. 2022;10:645.
- Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Dermatol. 2014;7(2 suppl):S3-S21.
- Webster GF, Leyden JJ, Gross JA. Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, treatment, crossover study. J Am Acad Dermatol. 2013;69:762-767.
- Del Rosso JQ, Stein Gold L, Seagal J, et al. An open-label, phase IV study evaluating Lidose-isotretinoin administered without food in patients with severe recalcitrant nodular acne: low relapse rates observed over the 104-week post-treatment period. J Clin Aesthet Dermatol. 2019;12:13-18.
- Wilkin J, Dahl M, Detmar M, et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol. 2002;46:584-587.
- Steinhoff M, Buddenkotte J, Aubert J, et al. Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011;15:2-11.
- Yamasaki K, Gallo RL. The molecular pathology of rosacea. J Dermatol Sci. 2009;55:77-81.
- Tanghetti E, Del Rosso JQ, Thiboutot D, et al. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 4: a status report on physical modalities and devices. Cutis. 2014;93:71-76.
- Del Rosso JQ, Gallo RL, Tanghetti E, et al. An evaluation of potential correlations between pathophysiologic mechanisms, clinical manifestations, and management of rosacea. Cutis. 2013;91(3 suppl):1-8.
- Schaller M, Almeida LMC, Bewley A, et al. Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel. Br J Dermatol. 2020;182:1269-1276.
- Xu H, Li H. Acne, the skin microbiome, and antibiotic treatment. Am J Clin Dermatol. 2019;20:335-344.
- Daou H, Paradiso M, Hennessy K. Rosacea and the microbiome: a systematic review. Dermatol Ther (Heidelb). 2021;11:1-12.
- Kayiran MA, Karadag AS, Al-Khuzaei S, et al. Antibiotic resistance in acne: mechanisms, complications and management. Am J Clin Dermatol. 2020;21:813-819.
Breakthroughs and challenges in hepatology
CHICAGO – The most notable is the progress from discovery of the hepatitis C virus (previously non-A, non-B hepatitis) in 1989 to a near 100% cure with 8-12 weeks of oral medications in just 30 years, culminating in the The Nobel Prize in Physiology or Medicine in 2020.
This remarkable feat is matched by the progress from discovery of the hepatitis B virus (initially coined Australia antigen) and a 1976 Nobel Prize to an effective vaccine in 1981, to a list of antiviral drugs approved beginning in 1992 (with currently available nucleos(t)ide analogues associated with near zero risk of antiviral drug resistance even when used as monotherapy), to demonstration that both hepatitis B vaccine and antivirals can prevent liver cancer. Other major breakthroughs include blood-based and image-based noninvasive assessment of liver fibrosis obviating the need for liver biopsy to stage liver disease, and multiple systemic therapies for advanced liver cancer.
However, there remain many challenges. While we have the tools to eliminate hepatitis B and hepatitis C, resources and coordinated efforts are needed to realize this feasible goal. Development of a vaccine for hepatitis C and a cure for hepatitis B will facilitate this goal.
The biggest present-day challenges in hepatology are the epidemics of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD), particularly since both are increasingly impacting young people, socially disadvantaged populations, and those with mental health problems. Social isolation and mental and financial stressors associated with the COVID pandemic have aggravated both NAFLD and ALD, which have now become the leading indications for liver transplantation. Multi-pronged approaches, including public policies and education, destigmatization, easy access to mental health care, provider training, and provision of multi-disciplinary care, are needed to curb this tsunami. NAFLD affects more than 30% of the global population, and screening with simple biomarker(s) followed by liver stiffness measurement using elastography has been proposed to identify patients with or at high risk of advanced fibrosis or cirrhosis for specialist care. NAFLD is a heterogeneous disease and the requirement for paired liver biopsies to demonstrate benefit have made drug development challenging. Better phenotyping of disease and surrogates for outcomes are needed. Liver cancer is one of the top cancer killers globally, but it is also a preventable cancer making prevention and early treatment of liver disease a top public health priority.
Dr. Lok is director of clinical hepatology and assistant dean for clinical research, University of Michigan Medical School, Ann Arbor. She disclosed research grants with AstraZeneca, Kowa, and Target. She has served as a consultant/adviser to Abbott, Chroma, GlaxoSmithKline, Roche, Virion, and Novo Nordisk. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – The most notable is the progress from discovery of the hepatitis C virus (previously non-A, non-B hepatitis) in 1989 to a near 100% cure with 8-12 weeks of oral medications in just 30 years, culminating in the The Nobel Prize in Physiology or Medicine in 2020.
This remarkable feat is matched by the progress from discovery of the hepatitis B virus (initially coined Australia antigen) and a 1976 Nobel Prize to an effective vaccine in 1981, to a list of antiviral drugs approved beginning in 1992 (with currently available nucleos(t)ide analogues associated with near zero risk of antiviral drug resistance even when used as monotherapy), to demonstration that both hepatitis B vaccine and antivirals can prevent liver cancer. Other major breakthroughs include blood-based and image-based noninvasive assessment of liver fibrosis obviating the need for liver biopsy to stage liver disease, and multiple systemic therapies for advanced liver cancer.
However, there remain many challenges. While we have the tools to eliminate hepatitis B and hepatitis C, resources and coordinated efforts are needed to realize this feasible goal. Development of a vaccine for hepatitis C and a cure for hepatitis B will facilitate this goal.
The biggest present-day challenges in hepatology are the epidemics of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD), particularly since both are increasingly impacting young people, socially disadvantaged populations, and those with mental health problems. Social isolation and mental and financial stressors associated with the COVID pandemic have aggravated both NAFLD and ALD, which have now become the leading indications for liver transplantation. Multi-pronged approaches, including public policies and education, destigmatization, easy access to mental health care, provider training, and provision of multi-disciplinary care, are needed to curb this tsunami. NAFLD affects more than 30% of the global population, and screening with simple biomarker(s) followed by liver stiffness measurement using elastography has been proposed to identify patients with or at high risk of advanced fibrosis or cirrhosis for specialist care. NAFLD is a heterogeneous disease and the requirement for paired liver biopsies to demonstrate benefit have made drug development challenging. Better phenotyping of disease and surrogates for outcomes are needed. Liver cancer is one of the top cancer killers globally, but it is also a preventable cancer making prevention and early treatment of liver disease a top public health priority.
Dr. Lok is director of clinical hepatology and assistant dean for clinical research, University of Michigan Medical School, Ann Arbor. She disclosed research grants with AstraZeneca, Kowa, and Target. She has served as a consultant/adviser to Abbott, Chroma, GlaxoSmithKline, Roche, Virion, and Novo Nordisk. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
CHICAGO – The most notable is the progress from discovery of the hepatitis C virus (previously non-A, non-B hepatitis) in 1989 to a near 100% cure with 8-12 weeks of oral medications in just 30 years, culminating in the The Nobel Prize in Physiology or Medicine in 2020.
This remarkable feat is matched by the progress from discovery of the hepatitis B virus (initially coined Australia antigen) and a 1976 Nobel Prize to an effective vaccine in 1981, to a list of antiviral drugs approved beginning in 1992 (with currently available nucleos(t)ide analogues associated with near zero risk of antiviral drug resistance even when used as monotherapy), to demonstration that both hepatitis B vaccine and antivirals can prevent liver cancer. Other major breakthroughs include blood-based and image-based noninvasive assessment of liver fibrosis obviating the need for liver biopsy to stage liver disease, and multiple systemic therapies for advanced liver cancer.
However, there remain many challenges. While we have the tools to eliminate hepatitis B and hepatitis C, resources and coordinated efforts are needed to realize this feasible goal. Development of a vaccine for hepatitis C and a cure for hepatitis B will facilitate this goal.
The biggest present-day challenges in hepatology are the epidemics of nonalcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD), particularly since both are increasingly impacting young people, socially disadvantaged populations, and those with mental health problems. Social isolation and mental and financial stressors associated with the COVID pandemic have aggravated both NAFLD and ALD, which have now become the leading indications for liver transplantation. Multi-pronged approaches, including public policies and education, destigmatization, easy access to mental health care, provider training, and provision of multi-disciplinary care, are needed to curb this tsunami. NAFLD affects more than 30% of the global population, and screening with simple biomarker(s) followed by liver stiffness measurement using elastography has been proposed to identify patients with or at high risk of advanced fibrosis or cirrhosis for specialist care. NAFLD is a heterogeneous disease and the requirement for paired liver biopsies to demonstrate benefit have made drug development challenging. Better phenotyping of disease and surrogates for outcomes are needed. Liver cancer is one of the top cancer killers globally, but it is also a preventable cancer making prevention and early treatment of liver disease a top public health priority.
Dr. Lok is director of clinical hepatology and assistant dean for clinical research, University of Michigan Medical School, Ann Arbor. She disclosed research grants with AstraZeneca, Kowa, and Target. She has served as a consultant/adviser to Abbott, Chroma, GlaxoSmithKline, Roche, Virion, and Novo Nordisk. These remarks were made during one of the AGA Postgraduate Course sessions held at DDW 2023. DDW is sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE) and The Society for Surgery of the Alimentary Tract (SSAT).
AT DDW 2023
Disconnecting to reconnect
I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.
For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.
In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.
For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.
In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
I recently returned from a bucket list trip rafting the full length of the Grand Canyon via the Colorado River. It was a spectacular trip, filled with thrilling rapids, awe-inspiring hikes through slot canyons, and swimming in the turquoise waters of Havasu Falls.
For those of you who are fortunate to have experienced a similar adventure, I think you’ll agree one of the best things about the trip (aside from the breathtaking scenery) was the ability to completely unplug. Not only did I travel without my trusty laptop, but cell service was nonexistent. The effect of this forced digital detox was magical. By mentally disconnecting from work without the constant ping of my email and EHR inbox, our group had deeper conversations and formed genuine connections without the distractions of technology. In the frenetically paced world of modern health care where clinicians are reachable wherever they are in the world (even on vacation) as the boundaries between work and life blur, there are increasingly fewer times like this when we can fully disconnect. Yet, periodically disconnecting from work is critical, particularly for the clinician community, which is grappling with increasing levels of burnout and its consequences. As you embark on your well-deserved summer vacations, I hope you have an opportunity to set aside your devices to reconnect more fully with your family and friends, but also yourself.
In this month’s issue of GI&Hepatology News, we update you on AGA’s ongoing advocacy efforts to challenge UnitedHealthcare’s plans to impose increased administrative burdens on GI practices relating to routine GI procedures. We also highlight a landmark clinical trial in pediatric Crohn’s disease recently published in Gastroenterology. In our quarterly Perspectives column, Dr. Mariam Naveed and Dr. Petr Protiva outline important considerations regarding when to stop surveillance for colorectal neoplasia in elderly patients. Finally, our July Member Spotlight features gastroenterologist Dr. Russ Arjal, who shares his experiences launching Telebelly Health, an entirely virtual GI practice.
Megan A. Adams, MD, JD, MSc
Editor-in-Chief
MD rushes in after lightning strikes four people at White House
It was one of those dog days of August where the humidity is palpable and the pressure is so hot and thick you can almost feel the ions in the air. At the time (2022), I was a White House fellow and senior adviser in the West Wing Office of Public Engagement and in the Office of the Vice President.
I was leaving the White House around 7:00 p.m. through the front gate on Lafayette Square. I had a dinner reservation with a friend, so I was in a rush. It was super overcast. Lo and behold, three steps after I closed the gate behind me, it started pouring. Rain came down so hard I had to take shelter.
There’s a stone building in front of the White House with archways, so I took cover underneath one of them, hoping that in a couple of minutes the rain would pass. Behind the archways are these thick, black, iron gates.
Just as I was about to make a run for it, I heard: BOOM!
It was like a bomb had gone off. In one moment, I saw the lightning bolt, heard the thunder, and felt the heat. It was all one rush of sensation. I couldn’t remember having been that scared in a long time.
I thought, “I definitely have to get out of here. In a couple of minutes there might be another strike, and I’m sitting next to iron gates!” I saw a little bit of a window in the downpour, so I started booking it. I knew there was a sheltered Secret Service area around the corner where they park their cars. A much safer place to be.
I was sprinting on the sidewalk and spotted a bunch of Secret Service agents on their bikes riding in the opposite direction, back toward the park. I knew they wouldn’t be out on bikes in this mess without a reason. As they reached me, one agent said, “Clear the sidewalk! We’re coming through with a bunch of equipment.”
I yelled, “What’s going on?”
“Four people were just struck by lightning,” he said as he zoomed past.
I thought: “Sh*t. I have to go back.”
It was like two different parts of my brain were active at the exact same time. My subcortical brain at the level of the amygdala was like: “You just ran from there, idiot. Why are you running back?” And another part of my brain was like: “This is who you are.”
The lightning had struck one of the largest trees in the park. Four bodies splayed out in one direction from the tree. They’d been taking shelter underneath it when they were hit and were blown off to one side. By the time I got there, two Secret Service agents were on the scene doing CPR. Some bystanders had started to run over.
I did a quick round of pulse checks to see everyone’s status, and all four were apneic and pulseless. I told the two Secret Service agents to keep doing compressions on the first person. Two bystanders also began compressions on another person, an older man.
More Secret Service agents arrived, and I said, “We need to do compressions on this other person right now.” One of the agents took a moment to question who I could be and why I was there. I said, “I’m a doctor. I know I’m not dressed like one, but I’m a physician.”
I told some agents to go find an AED, because these people needed to be shocked.
After they left, I was effectively trying to triage which of these four people would get the AED first. Initially, I spent more of my time on the young man, and we began to get some response from him. I then spent some time with the young woman.
It turned out there were AEDs in the pouches on the Secret Service bikes, but they were very small, dinky AEDs. We tried to apply the pads, but it was downpouring so much that the adhesive wouldn’t stick. I told one of the agents we needed a towel.
Through all this I was concerned we were going to be struck again. I mean, the metal statue of Lafayette was right there! They say lighting doesn’t strike in the same place twice, but who knows if that’s really true?
The towel arrived, and we were able to get the chests of the younger people dry enough for the AED pads. We applied two shocks first to the woman, then the young man. We got his pulse back quickly. The woman’s came back as well, but it felt much weaker.
EMS arrived shortly thereafter. We got all four patients on the transport, and they were transferred to the hospital.
The whole experience had taken 14 minutes.
At the time, I felt confident that the young man was going to survive. We’re taught that lightning bolt strikes are survivable if you can shock someone quickly. He also got pretty good CPR. But the next day I was watching the news and learned that he had passed away. So, of course I was thinking the worst about the others as well.
But a week and a half later, I learned that the young woman had been discharged from the ICU. She was the only one who made it. Her name is Amber, and we got connected through a reporter. About 2 weeks later, I invited her to the White House. I took her to the Oval Office. I met her mom and dad and husband, and we had dinner. We’ve been in touch ever since.
I remember the first time we talked on the phone, Amber said something along the lines of, “This sucks. Obviously, I was not planning for any of this to happen. But I also think there’s something good that could come from this.”
I was so surprised and happy to hear her say that. I had something similar happen to me when I was a teenager – caught in the wrong place at the wrong time. I tried to intervene in a gang fight in my neighborhood. I thought a kid was going to get killed, so I jumped in, imagining I could save the day. I didn’t. They broke a bunch of my bones and I was in the hospital for a bit.
I remember thinking then that my life was over. But after some time, I found a new perspective, which was: Maybe that life is over. But maybe this could be the beginning of a new one. And maybe those things that I’ve been afraid of doing, the dreams that I have, maybe now I’m actually free to go after them.
I told Amber, if there are things that you have been waiting to do, this could be the time. She wants to be an international human rights activist, and she is kicking butt in a graduate school program to begin on that pathway. It’s been really cool to watch her chase this dream with way more vigor than she had before.
I think we bonded because we’ve gone through – obviously not the same thing, but a similar moment of being confronted with your own mortality. Realizing that life can just shatter. And so, while we’re here, we might as well go for it with all the force of a person who knows this could all disappear in an instant.
It was an extremely humbling moment. It reaffirmed that my life is not about me. I have to use the time that I’ve got on behalf of other people as much as I can. What is my life about if not being useful?
Dr. Martin is an emergency medicine physician and faculty member at the MGH Center for Social Justice and Health Equity at Harvard Medical School, Boston.
A version of this article first appeared on Medscape.com.
It was one of those dog days of August where the humidity is palpable and the pressure is so hot and thick you can almost feel the ions in the air. At the time (2022), I was a White House fellow and senior adviser in the West Wing Office of Public Engagement and in the Office of the Vice President.
I was leaving the White House around 7:00 p.m. through the front gate on Lafayette Square. I had a dinner reservation with a friend, so I was in a rush. It was super overcast. Lo and behold, three steps after I closed the gate behind me, it started pouring. Rain came down so hard I had to take shelter.
There’s a stone building in front of the White House with archways, so I took cover underneath one of them, hoping that in a couple of minutes the rain would pass. Behind the archways are these thick, black, iron gates.
Just as I was about to make a run for it, I heard: BOOM!
It was like a bomb had gone off. In one moment, I saw the lightning bolt, heard the thunder, and felt the heat. It was all one rush of sensation. I couldn’t remember having been that scared in a long time.
I thought, “I definitely have to get out of here. In a couple of minutes there might be another strike, and I’m sitting next to iron gates!” I saw a little bit of a window in the downpour, so I started booking it. I knew there was a sheltered Secret Service area around the corner where they park their cars. A much safer place to be.
I was sprinting on the sidewalk and spotted a bunch of Secret Service agents on their bikes riding in the opposite direction, back toward the park. I knew they wouldn’t be out on bikes in this mess without a reason. As they reached me, one agent said, “Clear the sidewalk! We’re coming through with a bunch of equipment.”
I yelled, “What’s going on?”
“Four people were just struck by lightning,” he said as he zoomed past.
I thought: “Sh*t. I have to go back.”
It was like two different parts of my brain were active at the exact same time. My subcortical brain at the level of the amygdala was like: “You just ran from there, idiot. Why are you running back?” And another part of my brain was like: “This is who you are.”
The lightning had struck one of the largest trees in the park. Four bodies splayed out in one direction from the tree. They’d been taking shelter underneath it when they were hit and were blown off to one side. By the time I got there, two Secret Service agents were on the scene doing CPR. Some bystanders had started to run over.
I did a quick round of pulse checks to see everyone’s status, and all four were apneic and pulseless. I told the two Secret Service agents to keep doing compressions on the first person. Two bystanders also began compressions on another person, an older man.
More Secret Service agents arrived, and I said, “We need to do compressions on this other person right now.” One of the agents took a moment to question who I could be and why I was there. I said, “I’m a doctor. I know I’m not dressed like one, but I’m a physician.”
I told some agents to go find an AED, because these people needed to be shocked.
After they left, I was effectively trying to triage which of these four people would get the AED first. Initially, I spent more of my time on the young man, and we began to get some response from him. I then spent some time with the young woman.
It turned out there were AEDs in the pouches on the Secret Service bikes, but they were very small, dinky AEDs. We tried to apply the pads, but it was downpouring so much that the adhesive wouldn’t stick. I told one of the agents we needed a towel.
Through all this I was concerned we were going to be struck again. I mean, the metal statue of Lafayette was right there! They say lighting doesn’t strike in the same place twice, but who knows if that’s really true?
The towel arrived, and we were able to get the chests of the younger people dry enough for the AED pads. We applied two shocks first to the woman, then the young man. We got his pulse back quickly. The woman’s came back as well, but it felt much weaker.
EMS arrived shortly thereafter. We got all four patients on the transport, and they were transferred to the hospital.
The whole experience had taken 14 minutes.
At the time, I felt confident that the young man was going to survive. We’re taught that lightning bolt strikes are survivable if you can shock someone quickly. He also got pretty good CPR. But the next day I was watching the news and learned that he had passed away. So, of course I was thinking the worst about the others as well.
But a week and a half later, I learned that the young woman had been discharged from the ICU. She was the only one who made it. Her name is Amber, and we got connected through a reporter. About 2 weeks later, I invited her to the White House. I took her to the Oval Office. I met her mom and dad and husband, and we had dinner. We’ve been in touch ever since.
I remember the first time we talked on the phone, Amber said something along the lines of, “This sucks. Obviously, I was not planning for any of this to happen. But I also think there’s something good that could come from this.”
I was so surprised and happy to hear her say that. I had something similar happen to me when I was a teenager – caught in the wrong place at the wrong time. I tried to intervene in a gang fight in my neighborhood. I thought a kid was going to get killed, so I jumped in, imagining I could save the day. I didn’t. They broke a bunch of my bones and I was in the hospital for a bit.
I remember thinking then that my life was over. But after some time, I found a new perspective, which was: Maybe that life is over. But maybe this could be the beginning of a new one. And maybe those things that I’ve been afraid of doing, the dreams that I have, maybe now I’m actually free to go after them.
I told Amber, if there are things that you have been waiting to do, this could be the time. She wants to be an international human rights activist, and she is kicking butt in a graduate school program to begin on that pathway. It’s been really cool to watch her chase this dream with way more vigor than she had before.
I think we bonded because we’ve gone through – obviously not the same thing, but a similar moment of being confronted with your own mortality. Realizing that life can just shatter. And so, while we’re here, we might as well go for it with all the force of a person who knows this could all disappear in an instant.
It was an extremely humbling moment. It reaffirmed that my life is not about me. I have to use the time that I’ve got on behalf of other people as much as I can. What is my life about if not being useful?
Dr. Martin is an emergency medicine physician and faculty member at the MGH Center for Social Justice and Health Equity at Harvard Medical School, Boston.
A version of this article first appeared on Medscape.com.
It was one of those dog days of August where the humidity is palpable and the pressure is so hot and thick you can almost feel the ions in the air. At the time (2022), I was a White House fellow and senior adviser in the West Wing Office of Public Engagement and in the Office of the Vice President.
I was leaving the White House around 7:00 p.m. through the front gate on Lafayette Square. I had a dinner reservation with a friend, so I was in a rush. It was super overcast. Lo and behold, three steps after I closed the gate behind me, it started pouring. Rain came down so hard I had to take shelter.
There’s a stone building in front of the White House with archways, so I took cover underneath one of them, hoping that in a couple of minutes the rain would pass. Behind the archways are these thick, black, iron gates.
Just as I was about to make a run for it, I heard: BOOM!
It was like a bomb had gone off. In one moment, I saw the lightning bolt, heard the thunder, and felt the heat. It was all one rush of sensation. I couldn’t remember having been that scared in a long time.
I thought, “I definitely have to get out of here. In a couple of minutes there might be another strike, and I’m sitting next to iron gates!” I saw a little bit of a window in the downpour, so I started booking it. I knew there was a sheltered Secret Service area around the corner where they park their cars. A much safer place to be.
I was sprinting on the sidewalk and spotted a bunch of Secret Service agents on their bikes riding in the opposite direction, back toward the park. I knew they wouldn’t be out on bikes in this mess without a reason. As they reached me, one agent said, “Clear the sidewalk! We’re coming through with a bunch of equipment.”
I yelled, “What’s going on?”
“Four people were just struck by lightning,” he said as he zoomed past.
I thought: “Sh*t. I have to go back.”
It was like two different parts of my brain were active at the exact same time. My subcortical brain at the level of the amygdala was like: “You just ran from there, idiot. Why are you running back?” And another part of my brain was like: “This is who you are.”
The lightning had struck one of the largest trees in the park. Four bodies splayed out in one direction from the tree. They’d been taking shelter underneath it when they were hit and were blown off to one side. By the time I got there, two Secret Service agents were on the scene doing CPR. Some bystanders had started to run over.
I did a quick round of pulse checks to see everyone’s status, and all four were apneic and pulseless. I told the two Secret Service agents to keep doing compressions on the first person. Two bystanders also began compressions on another person, an older man.
More Secret Service agents arrived, and I said, “We need to do compressions on this other person right now.” One of the agents took a moment to question who I could be and why I was there. I said, “I’m a doctor. I know I’m not dressed like one, but I’m a physician.”
I told some agents to go find an AED, because these people needed to be shocked.
After they left, I was effectively trying to triage which of these four people would get the AED first. Initially, I spent more of my time on the young man, and we began to get some response from him. I then spent some time with the young woman.
It turned out there were AEDs in the pouches on the Secret Service bikes, but they were very small, dinky AEDs. We tried to apply the pads, but it was downpouring so much that the adhesive wouldn’t stick. I told one of the agents we needed a towel.
Through all this I was concerned we were going to be struck again. I mean, the metal statue of Lafayette was right there! They say lighting doesn’t strike in the same place twice, but who knows if that’s really true?
The towel arrived, and we were able to get the chests of the younger people dry enough for the AED pads. We applied two shocks first to the woman, then the young man. We got his pulse back quickly. The woman’s came back as well, but it felt much weaker.
EMS arrived shortly thereafter. We got all four patients on the transport, and they were transferred to the hospital.
The whole experience had taken 14 minutes.
At the time, I felt confident that the young man was going to survive. We’re taught that lightning bolt strikes are survivable if you can shock someone quickly. He also got pretty good CPR. But the next day I was watching the news and learned that he had passed away. So, of course I was thinking the worst about the others as well.
But a week and a half later, I learned that the young woman had been discharged from the ICU. She was the only one who made it. Her name is Amber, and we got connected through a reporter. About 2 weeks later, I invited her to the White House. I took her to the Oval Office. I met her mom and dad and husband, and we had dinner. We’ve been in touch ever since.
I remember the first time we talked on the phone, Amber said something along the lines of, “This sucks. Obviously, I was not planning for any of this to happen. But I also think there’s something good that could come from this.”
I was so surprised and happy to hear her say that. I had something similar happen to me when I was a teenager – caught in the wrong place at the wrong time. I tried to intervene in a gang fight in my neighborhood. I thought a kid was going to get killed, so I jumped in, imagining I could save the day. I didn’t. They broke a bunch of my bones and I was in the hospital for a bit.
I remember thinking then that my life was over. But after some time, I found a new perspective, which was: Maybe that life is over. But maybe this could be the beginning of a new one. And maybe those things that I’ve been afraid of doing, the dreams that I have, maybe now I’m actually free to go after them.
I told Amber, if there are things that you have been waiting to do, this could be the time. She wants to be an international human rights activist, and she is kicking butt in a graduate school program to begin on that pathway. It’s been really cool to watch her chase this dream with way more vigor than she had before.
I think we bonded because we’ve gone through – obviously not the same thing, but a similar moment of being confronted with your own mortality. Realizing that life can just shatter. And so, while we’re here, we might as well go for it with all the force of a person who knows this could all disappear in an instant.
It was an extremely humbling moment. It reaffirmed that my life is not about me. I have to use the time that I’ve got on behalf of other people as much as I can. What is my life about if not being useful?
Dr. Martin is an emergency medicine physician and faculty member at the MGH Center for Social Justice and Health Equity at Harvard Medical School, Boston.
A version of this article first appeared on Medscape.com.