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A cigarette in one hand and a Fitbit on the other
A cardiologist friend of mine told me a story about one of his patients. The man had recently been in to see him for an office visit. He had quite a scare needing two stents after an episode of prolonged chest pain and, during the office visit, apparently had said that he had “found religion” and was going to change his ways. He showed off the Fitbit that he had gotten and shared his excitement about using a new app to track his diet on his smart phone. His blood pressure was a little elevated, so my friend added a third antihypertensive in an effort to get his blood pressure under control. He referred the patient back to his primary care physician to address his elevated hemoglobin A1c.
My friend saw the patient again a couple of weeks later – this time at the mall. As he was driving through the parking lot, he noticed his patient sitting on a bench outside the entrance. He also noticed a cigarette in his patient’s right hand and saw the Fitbit still on his wrist. Now, it’s not that there is anything wrong with wearing a Fitbit, but …
My friend is an incredibly respectful person, and very nice. He decided not to say hello and risk embarrassing his patient, so he walked to a different door far from the bench and went inside. Nonetheless, the image bothered him. It bothered him enough to repeat the story to me 2 weeks later. It bothers me too.
The other day I was talking to a healthy young nurse with whom I work. She has been trying to get into shape, and her goal is to get to the gym 5 days a week after work. She read on a popular website that she should use a heart rate monitor to keep track of her training and that, if her heart rate is too slow, she should run faster and, if her heart rate is too fast, she should slow down. She was discouraged the other day, however, because her watch indicated that her pulse was going up to 170 while she was running hard, and she had heard that could be dangerous for her heart.
When she doesn’t push hard, though, she told me that her heart rate often plateaus at about 110, sometimes 115. She has been finding it difficult to achieve her calculated target heart rate of 120-160 beats per minute. She is frustrated and was going to skip her workout that evening. I explained to her that she should stop checking her pulse and just run – if she felt she was running too slow she could run faster.
With everything that we have learned about science and technology, the reality is that we are still people, with all our weaknesses and strengths. We often set goals with ambivalence, then rush forward hoping that a technological solution will move us in the direction we think we want to move. Unfortunately, owning a Fitbit will not make us more fit, and checking our pulse every five minutes while working out will not lead to a better exercise session. With the availability of so much technology for tracking our daily exercise, vital signs, and various other measures of health, we need to be more careful than ever to determine specifically what it is that we are trying to accomplish with the use of our technology.
When it comes to good health, it is the fundamentals that matter, and achieving the fundamentals requires being mindful and making repeated efforts to master them. For almost all adults, the most important habits to develop are still related to diet and exercise. Consuming the right diet and exercising adequately requires that the correct choices be made each and every day, all day long. Technology can help but will not do it for us. We need to be thoughtful about how we use technology and explicit about how we expect it to help. After a reasonable amount of time, we should evaluate to see if it is working for us. If it is, then we should continue to use it. If it is not, then we should stop using it or make a different change, like performing a new type of exercise.
Our goal should be to have intelligent empathic integration of technological and behavioral techniques to achieve an optimal health outcome. Putting running shoes by the bed at night is a great thing to do to encourage us to run in the morning. Choosing motivational music can help us get the energy and enthusiasm to go for that run (our favorites include the Rocky theme song and “I Didn’t Come this Far to Only Come this Far”). A visual reminder over the refrigerator can “nudge” us to make good choices as we open the door.
For those who want to learn more about how to integrate behavioral management into their advice for patients we highly recommend reading “Switch: How to Change Things When Change Is Hard” by Chip Heath and “Nudge: Improving Decisions About Health, Wealth, and Happiness” by Richard Thaler. We have always been, and remain, excited about the promise of technology to help us accomplish our goals. That said, we told the nurse to stop checking her pulse, to put on some music, and to appreciate the leaves on the trees this autumn while she was running. As for the gentleman outside the mall, well …
We are interested in your thoughts. Please email us at [email protected].
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on Twitter @doctornotte. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
A cardiologist friend of mine told me a story about one of his patients. The man had recently been in to see him for an office visit. He had quite a scare needing two stents after an episode of prolonged chest pain and, during the office visit, apparently had said that he had “found religion” and was going to change his ways. He showed off the Fitbit that he had gotten and shared his excitement about using a new app to track his diet on his smart phone. His blood pressure was a little elevated, so my friend added a third antihypertensive in an effort to get his blood pressure under control. He referred the patient back to his primary care physician to address his elevated hemoglobin A1c.
My friend saw the patient again a couple of weeks later – this time at the mall. As he was driving through the parking lot, he noticed his patient sitting on a bench outside the entrance. He also noticed a cigarette in his patient’s right hand and saw the Fitbit still on his wrist. Now, it’s not that there is anything wrong with wearing a Fitbit, but …
My friend is an incredibly respectful person, and very nice. He decided not to say hello and risk embarrassing his patient, so he walked to a different door far from the bench and went inside. Nonetheless, the image bothered him. It bothered him enough to repeat the story to me 2 weeks later. It bothers me too.
The other day I was talking to a healthy young nurse with whom I work. She has been trying to get into shape, and her goal is to get to the gym 5 days a week after work. She read on a popular website that she should use a heart rate monitor to keep track of her training and that, if her heart rate is too slow, she should run faster and, if her heart rate is too fast, she should slow down. She was discouraged the other day, however, because her watch indicated that her pulse was going up to 170 while she was running hard, and she had heard that could be dangerous for her heart.
When she doesn’t push hard, though, she told me that her heart rate often plateaus at about 110, sometimes 115. She has been finding it difficult to achieve her calculated target heart rate of 120-160 beats per minute. She is frustrated and was going to skip her workout that evening. I explained to her that she should stop checking her pulse and just run – if she felt she was running too slow she could run faster.
With everything that we have learned about science and technology, the reality is that we are still people, with all our weaknesses and strengths. We often set goals with ambivalence, then rush forward hoping that a technological solution will move us in the direction we think we want to move. Unfortunately, owning a Fitbit will not make us more fit, and checking our pulse every five minutes while working out will not lead to a better exercise session. With the availability of so much technology for tracking our daily exercise, vital signs, and various other measures of health, we need to be more careful than ever to determine specifically what it is that we are trying to accomplish with the use of our technology.
When it comes to good health, it is the fundamentals that matter, and achieving the fundamentals requires being mindful and making repeated efforts to master them. For almost all adults, the most important habits to develop are still related to diet and exercise. Consuming the right diet and exercising adequately requires that the correct choices be made each and every day, all day long. Technology can help but will not do it for us. We need to be thoughtful about how we use technology and explicit about how we expect it to help. After a reasonable amount of time, we should evaluate to see if it is working for us. If it is, then we should continue to use it. If it is not, then we should stop using it or make a different change, like performing a new type of exercise.
Our goal should be to have intelligent empathic integration of technological and behavioral techniques to achieve an optimal health outcome. Putting running shoes by the bed at night is a great thing to do to encourage us to run in the morning. Choosing motivational music can help us get the energy and enthusiasm to go for that run (our favorites include the Rocky theme song and “I Didn’t Come this Far to Only Come this Far”). A visual reminder over the refrigerator can “nudge” us to make good choices as we open the door.
For those who want to learn more about how to integrate behavioral management into their advice for patients we highly recommend reading “Switch: How to Change Things When Change Is Hard” by Chip Heath and “Nudge: Improving Decisions About Health, Wealth, and Happiness” by Richard Thaler. We have always been, and remain, excited about the promise of technology to help us accomplish our goals. That said, we told the nurse to stop checking her pulse, to put on some music, and to appreciate the leaves on the trees this autumn while she was running. As for the gentleman outside the mall, well …
We are interested in your thoughts. Please email us at [email protected].
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on Twitter @doctornotte. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
A cardiologist friend of mine told me a story about one of his patients. The man had recently been in to see him for an office visit. He had quite a scare needing two stents after an episode of prolonged chest pain and, during the office visit, apparently had said that he had “found religion” and was going to change his ways. He showed off the Fitbit that he had gotten and shared his excitement about using a new app to track his diet on his smart phone. His blood pressure was a little elevated, so my friend added a third antihypertensive in an effort to get his blood pressure under control. He referred the patient back to his primary care physician to address his elevated hemoglobin A1c.
My friend saw the patient again a couple of weeks later – this time at the mall. As he was driving through the parking lot, he noticed his patient sitting on a bench outside the entrance. He also noticed a cigarette in his patient’s right hand and saw the Fitbit still on his wrist. Now, it’s not that there is anything wrong with wearing a Fitbit, but …
My friend is an incredibly respectful person, and very nice. He decided not to say hello and risk embarrassing his patient, so he walked to a different door far from the bench and went inside. Nonetheless, the image bothered him. It bothered him enough to repeat the story to me 2 weeks later. It bothers me too.
The other day I was talking to a healthy young nurse with whom I work. She has been trying to get into shape, and her goal is to get to the gym 5 days a week after work. She read on a popular website that she should use a heart rate monitor to keep track of her training and that, if her heart rate is too slow, she should run faster and, if her heart rate is too fast, she should slow down. She was discouraged the other day, however, because her watch indicated that her pulse was going up to 170 while she was running hard, and she had heard that could be dangerous for her heart.
When she doesn’t push hard, though, she told me that her heart rate often plateaus at about 110, sometimes 115. She has been finding it difficult to achieve her calculated target heart rate of 120-160 beats per minute. She is frustrated and was going to skip her workout that evening. I explained to her that she should stop checking her pulse and just run – if she felt she was running too slow she could run faster.
With everything that we have learned about science and technology, the reality is that we are still people, with all our weaknesses and strengths. We often set goals with ambivalence, then rush forward hoping that a technological solution will move us in the direction we think we want to move. Unfortunately, owning a Fitbit will not make us more fit, and checking our pulse every five minutes while working out will not lead to a better exercise session. With the availability of so much technology for tracking our daily exercise, vital signs, and various other measures of health, we need to be more careful than ever to determine specifically what it is that we are trying to accomplish with the use of our technology.
When it comes to good health, it is the fundamentals that matter, and achieving the fundamentals requires being mindful and making repeated efforts to master them. For almost all adults, the most important habits to develop are still related to diet and exercise. Consuming the right diet and exercising adequately requires that the correct choices be made each and every day, all day long. Technology can help but will not do it for us. We need to be thoughtful about how we use technology and explicit about how we expect it to help. After a reasonable amount of time, we should evaluate to see if it is working for us. If it is, then we should continue to use it. If it is not, then we should stop using it or make a different change, like performing a new type of exercise.
Our goal should be to have intelligent empathic integration of technological and behavioral techniques to achieve an optimal health outcome. Putting running shoes by the bed at night is a great thing to do to encourage us to run in the morning. Choosing motivational music can help us get the energy and enthusiasm to go for that run (our favorites include the Rocky theme song and “I Didn’t Come this Far to Only Come this Far”). A visual reminder over the refrigerator can “nudge” us to make good choices as we open the door.
For those who want to learn more about how to integrate behavioral management into their advice for patients we highly recommend reading “Switch: How to Change Things When Change Is Hard” by Chip Heath and “Nudge: Improving Decisions About Health, Wealth, and Happiness” by Richard Thaler. We have always been, and remain, excited about the promise of technology to help us accomplish our goals. That said, we told the nurse to stop checking her pulse, to put on some music, and to appreciate the leaves on the trees this autumn while she was running. As for the gentleman outside the mall, well …
We are interested in your thoughts. Please email us at [email protected].
Dr. Notte is a family physician and associate chief medical information officer for Abington (Pa.) Jefferson Health. Follow him on Twitter @doctornotte. Dr. Skolnik is professor of family and community medicine at Jefferson Medical College, Philadelphia, and an associate director of the family medicine residency program at Abington Jefferson Health.
Will changing the names of psychiatric medications lead to better treatment?
Back in 1980, the American Psychiatric Association dropped the word “neurosis” from the DSM-III, so that if you had been neurotic, after 1980, you were neurotic no longer.
At the time, I discussed this on my daily radio show. For those folks who were nervous, worried, fearful, and full of anxieties about themselves, their families, welfare, health, and the environment around them, a new set of labels was introduced to more specifically describe one or more problems related to anxiety.
For codification, and at times, a clearer understanding of a specific problem, the change was made to be helpful. Certainly, for insurers and pharmacologic treatments, it worked. However, it’s interesting that the word and concept, neurosis, which still is used by some psychiatrists and psychologists – although not scientific – does offer a clear overall picture of a suffering, anxiety-ridden person who might have a combination of an anxiety disorder, panic attacks, somatic symptoms, and endless worry. This overlapping picture often is seen in clinical practice more than the multiple one-dimensional labels that are currently used. So be it.
This all leads me to what I’ve recently learned about the Neuroscience-based Nomenclature (NbN) Project. According to a recent article in the APA’s Psychiatric News, the group’s board of trustees has endorsed a proposal that would change or revise the names of psychiatric medications so that the names reflect their mechanism of action – a move seemingly focused on a pure biological model.
For example, according to the article, the medication perphenazine would be renamed a “D2 receptor antagonist” rather than an antipsychotic. For depression, we might have a serotonergic reuptake inhibitor, according to the report, and of course, the list of changes would go on – based on current knowledge of biological activity. It’s true that in general medicine, there are examples where mode of action is discussed. For example, in cardiology we have beta-blockers and alpha-blockers, which are descriptive of their actions. As doctors who have trained for years and know the mechanism of action of various medications, we will understand all this. But in patient care, both doctors and their patients often understand and feel comfortable using descriptive terms indicating the treatment modality, such as antibiotics, antivirals, antifungals, anti-inflammatory medications, as well as anti-itching, antiaging, and antispasmodic drugs.
So, I am concerned about these proposed changes. In an era focused on patient-centered care, where we seek to make it simpler for the patient/health care consumer, we might make it harder for the patient to grasp what’s going on.
It’s very important to keep in mind that we as physicians know the ins and outs of medications, and that even the most educated and bright patients who are not in medicine do not know what our education has taught us. For example, regardless of specialty, we all know the difference between left-sided and right-sided heart failure. Those outside of medicine, however, rarely know the difference. They understand heart disease as a rule. People in general might understand some general concepts, such as RBC, WBC, and platelets. A patient will speak of taking a blood thinner but rarely know or understand the differences between antiplatelets and anticoagulants. And why should they know this? 
The point here is that I believe good patient care is keeping it simple and taking the time to explain what’s being treated, aiming to inform patients using down-to-earth, accessible language rather than the language of biochemistry.
It’s true that in psychiatry, wider use of certain medications than originally indicated has grown tremendously as well as off-label use. In light of that, the NbN idea is laudable. However, it would seem more practical to leave the traditional modes of action in place and expand our discussions with patients as to why we are using a specific medication. I have found a very simple and even rewarding way to explain to patients, for example, that yes, this is an antiseizure medication but it is now used in psychiatry as a mood stabilizer.
Another important point is the question of whether using nomenclature that describes the exact location of the problem is all that accurate. Currently, we know we still have a lot to learn about brain chemistry and neuronal transmission in mental disorders, just as in many medical disorders, there are gaps in our understanding of many illnesses and subsequent molecular changes.
Just as the DSM-III left behind the all-encompassing and descriptive word neurosis and the APA has changed labels in the DSM-IV and DSM-5, so the NbN project would change the nomenclature of current psychotropic medications. The intentions are good, but the idea that those changes will foster better patient understanding defies common sense. A better idea might be to continue use of both scientific names and names of commonly used actions of the medications, leaving both in place and letting clinicians decide what nomenclature best suits each patient.
It will be a sad day when psychiatrists become so medically and “scientifically” driven that we cannot explain to a patient, “I’m prescribing this antidepressant because it’s now used to treat anxiety,” or “Yes, this medicine is labeled ‘antipsychotic,’ but you’re not psychotic. It may help your mood swings and may even help you sleep better.” Now, is that hard? Is talking to a person and explaining the treatment no longer part of care? The take-home messages from the recent APA/Institute of Psychiatric Services meeting I attended seemed to suggest that human attention and care have great value. My father, a surgeon, always said that you learn a lot by simply talking to patients – and they learn from you.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019).
Back in 1980, the American Psychiatric Association dropped the word “neurosis” from the DSM-III, so that if you had been neurotic, after 1980, you were neurotic no longer.
At the time, I discussed this on my daily radio show. For those folks who were nervous, worried, fearful, and full of anxieties about themselves, their families, welfare, health, and the environment around them, a new set of labels was introduced to more specifically describe one or more problems related to anxiety.
For codification, and at times, a clearer understanding of a specific problem, the change was made to be helpful. Certainly, for insurers and pharmacologic treatments, it worked. However, it’s interesting that the word and concept, neurosis, which still is used by some psychiatrists and psychologists – although not scientific – does offer a clear overall picture of a suffering, anxiety-ridden person who might have a combination of an anxiety disorder, panic attacks, somatic symptoms, and endless worry. This overlapping picture often is seen in clinical practice more than the multiple one-dimensional labels that are currently used. So be it.
This all leads me to what I’ve recently learned about the Neuroscience-based Nomenclature (NbN) Project. According to a recent article in the APA’s Psychiatric News, the group’s board of trustees has endorsed a proposal that would change or revise the names of psychiatric medications so that the names reflect their mechanism of action – a move seemingly focused on a pure biological model.
For example, according to the article, the medication perphenazine would be renamed a “D2 receptor antagonist” rather than an antipsychotic. For depression, we might have a serotonergic reuptake inhibitor, according to the report, and of course, the list of changes would go on – based on current knowledge of biological activity. It’s true that in general medicine, there are examples where mode of action is discussed. For example, in cardiology we have beta-blockers and alpha-blockers, which are descriptive of their actions. As doctors who have trained for years and know the mechanism of action of various medications, we will understand all this. But in patient care, both doctors and their patients often understand and feel comfortable using descriptive terms indicating the treatment modality, such as antibiotics, antivirals, antifungals, anti-inflammatory medications, as well as anti-itching, antiaging, and antispasmodic drugs.
So, I am concerned about these proposed changes. In an era focused on patient-centered care, where we seek to make it simpler for the patient/health care consumer, we might make it harder for the patient to grasp what’s going on.
It’s very important to keep in mind that we as physicians know the ins and outs of medications, and that even the most educated and bright patients who are not in medicine do not know what our education has taught us. For example, regardless of specialty, we all know the difference between left-sided and right-sided heart failure. Those outside of medicine, however, rarely know the difference. They understand heart disease as a rule. People in general might understand some general concepts, such as RBC, WBC, and platelets. A patient will speak of taking a blood thinner but rarely know or understand the differences between antiplatelets and anticoagulants. And why should they know this?
The point here is that I believe good patient care is keeping it simple and taking the time to explain what’s being treated, aiming to inform patients using down-to-earth, accessible language rather than the language of biochemistry.
It’s true that in psychiatry, wider use of certain medications than originally indicated has grown tremendously as well as off-label use. In light of that, the NbN idea is laudable. However, it would seem more practical to leave the traditional modes of action in place and expand our discussions with patients as to why we are using a specific medication. I have found a very simple and even rewarding way to explain to patients, for example, that yes, this is an antiseizure medication but it is now used in psychiatry as a mood stabilizer.
Another important point is the question of whether using nomenclature that describes the exact location of the problem is all that accurate. Currently, we know we still have a lot to learn about brain chemistry and neuronal transmission in mental disorders, just as in many medical disorders, there are gaps in our understanding of many illnesses and subsequent molecular changes.
Just as the DSM-III left behind the all-encompassing and descriptive word neurosis and the APA has changed labels in the DSM-IV and DSM-5, so the NbN project would change the nomenclature of current psychotropic medications. The intentions are good, but the idea that those changes will foster better patient understanding defies common sense. A better idea might be to continue use of both scientific names and names of commonly used actions of the medications, leaving both in place and letting clinicians decide what nomenclature best suits each patient.
It will be a sad day when psychiatrists become so medically and “scientifically” driven that we cannot explain to a patient, “I’m prescribing this antidepressant because it’s now used to treat anxiety,” or “Yes, this medicine is labeled ‘antipsychotic,’ but you’re not psychotic. It may help your mood swings and may even help you sleep better.” Now, is that hard? Is talking to a person and explaining the treatment no longer part of care? The take-home messages from the recent APA/Institute of Psychiatric Services meeting I attended seemed to suggest that human attention and care have great value. My father, a surgeon, always said that you learn a lot by simply talking to patients – and they learn from you.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019).
Back in 1980, the American Psychiatric Association dropped the word “neurosis” from the DSM-III, so that if you had been neurotic, after 1980, you were neurotic no longer.
At the time, I discussed this on my daily radio show. For those folks who were nervous, worried, fearful, and full of anxieties about themselves, their families, welfare, health, and the environment around them, a new set of labels was introduced to more specifically describe one or more problems related to anxiety.
For codification, and at times, a clearer understanding of a specific problem, the change was made to be helpful. Certainly, for insurers and pharmacologic treatments, it worked. However, it’s interesting that the word and concept, neurosis, which still is used by some psychiatrists and psychologists – although not scientific – does offer a clear overall picture of a suffering, anxiety-ridden person who might have a combination of an anxiety disorder, panic attacks, somatic symptoms, and endless worry. This overlapping picture often is seen in clinical practice more than the multiple one-dimensional labels that are currently used. So be it.
This all leads me to what I’ve recently learned about the Neuroscience-based Nomenclature (NbN) Project. According to a recent article in the APA’s Psychiatric News, the group’s board of trustees has endorsed a proposal that would change or revise the names of psychiatric medications so that the names reflect their mechanism of action – a move seemingly focused on a pure biological model.
For example, according to the article, the medication perphenazine would be renamed a “D2 receptor antagonist” rather than an antipsychotic. For depression, we might have a serotonergic reuptake inhibitor, according to the report, and of course, the list of changes would go on – based on current knowledge of biological activity. It’s true that in general medicine, there are examples where mode of action is discussed. For example, in cardiology we have beta-blockers and alpha-blockers, which are descriptive of their actions. As doctors who have trained for years and know the mechanism of action of various medications, we will understand all this. But in patient care, both doctors and their patients often understand and feel comfortable using descriptive terms indicating the treatment modality, such as antibiotics, antivirals, antifungals, anti-inflammatory medications, as well as anti-itching, antiaging, and antispasmodic drugs.
So, I am concerned about these proposed changes. In an era focused on patient-centered care, where we seek to make it simpler for the patient/health care consumer, we might make it harder for the patient to grasp what’s going on.
It’s very important to keep in mind that we as physicians know the ins and outs of medications, and that even the most educated and bright patients who are not in medicine do not know what our education has taught us. For example, regardless of specialty, we all know the difference between left-sided and right-sided heart failure. Those outside of medicine, however, rarely know the difference. They understand heart disease as a rule. People in general might understand some general concepts, such as RBC, WBC, and platelets. A patient will speak of taking a blood thinner but rarely know or understand the differences between antiplatelets and anticoagulants. And why should they know this?
The point here is that I believe good patient care is keeping it simple and taking the time to explain what’s being treated, aiming to inform patients using down-to-earth, accessible language rather than the language of biochemistry.
It’s true that in psychiatry, wider use of certain medications than originally indicated has grown tremendously as well as off-label use. In light of that, the NbN idea is laudable. However, it would seem more practical to leave the traditional modes of action in place and expand our discussions with patients as to why we are using a specific medication. I have found a very simple and even rewarding way to explain to patients, for example, that yes, this is an antiseizure medication but it is now used in psychiatry as a mood stabilizer.
Another important point is the question of whether using nomenclature that describes the exact location of the problem is all that accurate. Currently, we know we still have a lot to learn about brain chemistry and neuronal transmission in mental disorders, just as in many medical disorders, there are gaps in our understanding of many illnesses and subsequent molecular changes.
Just as the DSM-III left behind the all-encompassing and descriptive word neurosis and the APA has changed labels in the DSM-IV and DSM-5, so the NbN project would change the nomenclature of current psychotropic medications. The intentions are good, but the idea that those changes will foster better patient understanding defies common sense. A better idea might be to continue use of both scientific names and names of commonly used actions of the medications, leaving both in place and letting clinicians decide what nomenclature best suits each patient.
It will be a sad day when psychiatrists become so medically and “scientifically” driven that we cannot explain to a patient, “I’m prescribing this antidepressant because it’s now used to treat anxiety,” or “Yes, this medicine is labeled ‘antipsychotic,’ but you’re not psychotic. It may help your mood swings and may even help you sleep better.” Now, is that hard? Is talking to a person and explaining the treatment no longer part of care? The take-home messages from the recent APA/Institute of Psychiatric Services meeting I attended seemed to suggest that human attention and care have great value. My father, a surgeon, always said that you learn a lot by simply talking to patients – and they learn from you.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019).
Is carpal tunnel syndrome the tip of the iceberg?
He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.
A cardiac examination found normal heart sounds with no murmurs.
A chest examination found dullness to percussion at both bases and rales.
A chest x-ray showed bilateral effusions and mild pulmonary edema.
The brain natriuretic peptide test found a level of 1,300 picograms/mL.
An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.
What history would be the most helpful in making a diagnosis?
A. History of prostate cancer
B. History of carpal tunnel syndrome
C. History of playing professional football
D. History of hyperlipidemia
E. History of ulcerative colitis
The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.
This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.
Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.
CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.
Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2
Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3
In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.
The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.
Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.
2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.
3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.
4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.
A cardiac examination found normal heart sounds with no murmurs.
A chest examination found dullness to percussion at both bases and rales.
A chest x-ray showed bilateral effusions and mild pulmonary edema.
The brain natriuretic peptide test found a level of 1,300 picograms/mL.
An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.
What history would be the most helpful in making a diagnosis?
A. History of prostate cancer
B. History of carpal tunnel syndrome
C. History of playing professional football
D. History of hyperlipidemia
E. History of ulcerative colitis
The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.
This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.
Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.
CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.
Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2
Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3
In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.
The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.
Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.
2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.
3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.
4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
He takes the following medications: felodipine and atorvastatin. On exam, his blood pressure is 110/60 mm Hg, and his pulse is 90 beats per minute.
A cardiac examination found normal heart sounds with no murmurs.
A chest examination found dullness to percussion at both bases and rales.
A chest x-ray showed bilateral effusions and mild pulmonary edema.
The brain natriuretic peptide test found a level of 1,300 picograms/mL.
An ECG found increased ventricular wall thickness, an ejection fraction of 32%, and normal aortic and mitral valves.
What history would be the most helpful in making a diagnosis?
A. History of prostate cancer
B. History of carpal tunnel syndrome
C. History of playing professional football
D. History of hyperlipidemia
E. History of ulcerative colitis
The correct answer here would be B. history of carpal tunnel syndrome (CTS). This patient has clinical heart failure, without a history of clinical ischemic disease. The differential diagnosis for causes of heart failure is long, with the most common causes being chronic hypertension and ischemic heart disease. Other common causes include chronic untreated sleep apnea and valvular heart disease.
This patient really does not have clear reasons for having clinical heart failure. His cardiovascular risk factors have been well controlled, and no valvular disease was found on ECG.
Several recent reports have raised the importance of a history of CTS significantly increasing the likelihood of amyloidosis being the cause of underlying heart failure.
CTS is such a common clinical entity that it is easy to not appreciate its presence as a clue to possible amyloid cardiomyopathy. Fosbøl et al. reported that a diagnosis of CTS was associated with a higher incidence of heart failure (hazard ratio, 1.54; CI, 1.45-1.64).1 They found a highly increased risk of amyloid (HR, 12.2) in patients who had surgery for CTS.
Sperry et al. found that over 10% of patients who underwent carpal tunnel release stained for amyloid on biopsy specimens, and that concomitant cardiac evaluation identified patients with cardiac involvement.2
Pinney et al. found that 48% of patients with transthyretin amyloidosis had a history of CTS.3
In a retrospective study of patients with wild-type transthyretin amyloid (253), patients with hereditary transthyretin amyloid (136), and asymptomatic gene carriers (77), participants were screened for a history of spinal stenosis and CTS.4 Almost 60% of the patients with amyloid had a history of CTS, and 11% had a history of spinal stenosis. Patients with CTS and hereditary amyloid had thicker interventricular septums, higher left ventricular mass, and lower Karnovsky index than those without CTS.
The diagnosis of CTS, especially in those who need surgery for treatment or have bilateral disease, should make us consider the possibility of underlying amyloidosis.
Pearl: In patients who have heart failure and a history of CTS, amyloidosis should be considered as a cause.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at that university. Contact Dr. Paauw at [email protected].
References
1. Fosbøl EL et al. J Am Coll Cardiol. 2019;74:15-23.
2. Sperry BW et al. J Am Coll Cardiol. 2018 Oct 23;72(17):2040-50.
3. Pinney JH et al. J Am Heart Assoc. 2013 Apr 22;2(2):e000098.
4. Aus dem Siepen F et al. Clin Res Cardiol. 2019 Apr 5. doi: 10.1007/s00392-019-01467-1.
Flu vaccine: Larger impact on influenza burden than you thought?
ID Week, the annual meeting of the Infectious Disease Society of America, provided valuable insights into past season’s endemic influenza burden and the effectiveness of prevention strategies. Each year, there are from 9million to 49 million influenza cases in the United States, 140,000-960,000 hospitalized cases, and 12,000-70,000 deaths directly attributable to influenza infection. The burden disproportionately falls on infants and adults 65 years of age and older; 11,000-48,000 children are hospitalized, and as many as several hundred children may die from influenza and related complications. School age children (aged 5-19 years) and adults (aged 30-39 years) are a major part of the transmission cycle. Influenza vaccine underlies the prevention strategy for limiting the burden of disease in U.S. populations. ID Week provided new insights into critical questions about influenza vaccines.
1. What is the effectiveness of influenza vaccine against severe disease (hospitalization) in children? Does it vary by age? By type or subtype?
Angela P. Campbell, MD, MPH, of the Centers for Disease Control and Prevention, and associates presented data on influenza vaccine effectiveness from the New Vaccine Surveillance Network in children for the 2016-2017 and 2017-2018 season (ID Week session 99; Abstract 899). During both 2016-2017 and 2017-2018, H3N2 was the dominant virus and influenza B represented about one-third of cases, and H1N1 was a greater percentage of cases in 2017-2018. Influenza positivity among children younger than 18 years of age admitted to hospital with respiratory disease was 14% among unvaccinated and 8% among vaccinated children; effectiveness again hospitalization was 50%. Vaccine effectiveness (VE) was not statistically different between children younger than 8 years of age and those older that 8 years but did differ by vaccine type. VE was 76% against H1N1 disease, 59% again B disease, and only 33% against H3N2 disease.
Clearly, vaccination with influenza vaccine prevents serious respiratory disease. However, the impact of vaccine will vary by season and by which influenza stains are circulating in the community. The authors concluded that further understanding of the lower VE against H3N2 disease is needed.
2. Does the priming dose of influenza vaccine improve vaccine effectiveness?
Current recommendations call for a two-dose series for influenza vaccine in children aged 6 months through 8 years who have not had prior influenza vaccine. The recommendation is based on evidence demonstrating higher antibody responses in children receiving two doses, compared with a single dose. Using data from the U.S. Influenza Vaccine Effectiveness Network, Jessie R. Chung, MPH, of the CDC, and associates compared VE in children younger than 2 years receiving two doses in the first year of flu immunization (fully immunized), compared with those who received only one dose (partially immunized) (ID Week session 99; Abstract 900). VE was 53% for fully immunized and 23% for partially immunized children. Receipt of a single dose did not provide statistically significant protection against influenza. Surprisingly (to me), of 5,355 children aged 6 months to less than 2 years with no prior influenza vaccine, 1,870 (35%) received only one dose in the season.
The data strongly support the current recommendations for a priming dose, especially in young children, in the first season of influenza vaccine and warrants increased efforts to increase the update of second doses during the season. Hopefully we can do better in 2019!
3. Should we wait to vaccinate with influenza vaccine?
Some evidence suggests that waning immunity to influenza vaccine, primarily in those aged 65 years and older, may explain increased disease activity toward the end of influenza season. Other explanations include increasing viral diversity throughout the season, resulting in reduced effectiveness. Do such concerns warrant delaying immunization? The onset and peak of influenza season varies by year; in October 2019, 3% of tests performed on patients with respiratory illness were influenza positive. The trade-offs for delaying immunization until October are the unpredictability of onset of influenza season, the requirement for two doses in infants, the need for 2 weeks to achieve peak antibody concentrations, and the potential that fewer individuals will be vaccinated. Kathy Neuzil, MD, MPH, from the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, reviewed recent modeling (for adults aged 65 years and older) and reported that delaying vaccine programs until October is associated with greater burden of hospitalization if 14% fewer individuals (who would be vaccinated in August/September) are vaccinated (ID Week; Session 940).
In response to these concerns, the CDC recommendations for 2019 are that, in children aged 6 months through 8 years who need two doses, start early so that you can achieve both doses before influenza season (MMWR 2019 Aug 23;68[3]:1-21).In older children and adults, who need only a single dose, early vaccination (August and early September) may lead to reduced protection late in the influenza season?
4. How can we optimize vaccine impact?
Vaccine impact refers to the affect on a population level and not at an individual level. Meagan C. Fitzpatrick, PhD, from the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, evaluated the benefits of our moderately effective influenza vaccines (VE 40%-60%) to the population beyond those who are vaccinated. Her conclusions were that even a modestly effective vaccine prevents 21 million cases of influenza, 129,000 hospitalizations, and 62,000 deaths. And that two-thirds of the deaths prevented are from herd benefit (or indirect effects). Although both coverage and vaccine effectiveness are important, she reported that population impact was most sensitive to coverage, compared with vaccine effectiveness. Dr. Fitzpatrick found that targeting school-age children 6-19 years of age and adults 30-39 years of age maximizes the public health benefits (herd effects) of influenza vaccine. In 2018 season, influenza coverage was 63% for at least one dose in children aged 6 months through 17 years and 45% in adults aged 18 years and older; in the two target age groups 5-17 and 30-39 years, coverage was 59% and approximately 35%, respectively (ID Week; Session 939).
Clearly, even our modestly effective influenza vaccines have significant public health benefit in protecting the U.S. populations from serious disease and death. Efforts to increase vaccine uptake in school-age children, both those with and without comorbidity, and the 30- to 39-year-old adult cohort would likely further reduce the burden of serious disease from influenza.
In summary, despite a vaccine that is only moderately effective, there is clear evidence to support current recommendations of universal immunization beginning at 6 months of age. Delaying until October 1 is a good idea only if the same number of individuals will receive influenza vaccine, otherwise the hypothetical benefit is lost.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and is senior attending physician, Boston Medical Center. Dr. Pelton has investigator-initiated research awards to Boston Medical Center from Pfizer and Merck Vaccines. He also received honorarium as an advisory board member, participation in symposium and consultation from Seqirus and Merck Vaccine, Pfizer, and Sanofi Pasteur. Email him at [email protected].
ID Week, the annual meeting of the Infectious Disease Society of America, provided valuable insights into past season’s endemic influenza burden and the effectiveness of prevention strategies. Each year, there are from 9million to 49 million influenza cases in the United States, 140,000-960,000 hospitalized cases, and 12,000-70,000 deaths directly attributable to influenza infection. The burden disproportionately falls on infants and adults 65 years of age and older; 11,000-48,000 children are hospitalized, and as many as several hundred children may die from influenza and related complications. School age children (aged 5-19 years) and adults (aged 30-39 years) are a major part of the transmission cycle. Influenza vaccine underlies the prevention strategy for limiting the burden of disease in U.S. populations. ID Week provided new insights into critical questions about influenza vaccines.
1. What is the effectiveness of influenza vaccine against severe disease (hospitalization) in children? Does it vary by age? By type or subtype?
Angela P. Campbell, MD, MPH, of the Centers for Disease Control and Prevention, and associates presented data on influenza vaccine effectiveness from the New Vaccine Surveillance Network in children for the 2016-2017 and 2017-2018 season (ID Week session 99; Abstract 899). During both 2016-2017 and 2017-2018, H3N2 was the dominant virus and influenza B represented about one-third of cases, and H1N1 was a greater percentage of cases in 2017-2018. Influenza positivity among children younger than 18 years of age admitted to hospital with respiratory disease was 14% among unvaccinated and 8% among vaccinated children; effectiveness again hospitalization was 50%. Vaccine effectiveness (VE) was not statistically different between children younger than 8 years of age and those older that 8 years but did differ by vaccine type. VE was 76% against H1N1 disease, 59% again B disease, and only 33% against H3N2 disease.
Clearly, vaccination with influenza vaccine prevents serious respiratory disease. However, the impact of vaccine will vary by season and by which influenza stains are circulating in the community. The authors concluded that further understanding of the lower VE against H3N2 disease is needed.
2. Does the priming dose of influenza vaccine improve vaccine effectiveness?
Current recommendations call for a two-dose series for influenza vaccine in children aged 6 months through 8 years who have not had prior influenza vaccine. The recommendation is based on evidence demonstrating higher antibody responses in children receiving two doses, compared with a single dose. Using data from the U.S. Influenza Vaccine Effectiveness Network, Jessie R. Chung, MPH, of the CDC, and associates compared VE in children younger than 2 years receiving two doses in the first year of flu immunization (fully immunized), compared with those who received only one dose (partially immunized) (ID Week session 99; Abstract 900). VE was 53% for fully immunized and 23% for partially immunized children. Receipt of a single dose did not provide statistically significant protection against influenza. Surprisingly (to me), of 5,355 children aged 6 months to less than 2 years with no prior influenza vaccine, 1,870 (35%) received only one dose in the season.
The data strongly support the current recommendations for a priming dose, especially in young children, in the first season of influenza vaccine and warrants increased efforts to increase the update of second doses during the season. Hopefully we can do better in 2019!
3. Should we wait to vaccinate with influenza vaccine?
Some evidence suggests that waning immunity to influenza vaccine, primarily in those aged 65 years and older, may explain increased disease activity toward the end of influenza season. Other explanations include increasing viral diversity throughout the season, resulting in reduced effectiveness. Do such concerns warrant delaying immunization? The onset and peak of influenza season varies by year; in October 2019, 3% of tests performed on patients with respiratory illness were influenza positive. The trade-offs for delaying immunization until October are the unpredictability of onset of influenza season, the requirement for two doses in infants, the need for 2 weeks to achieve peak antibody concentrations, and the potential that fewer individuals will be vaccinated. Kathy Neuzil, MD, MPH, from the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, reviewed recent modeling (for adults aged 65 years and older) and reported that delaying vaccine programs until October is associated with greater burden of hospitalization if 14% fewer individuals (who would be vaccinated in August/September) are vaccinated (ID Week; Session 940).
In response to these concerns, the CDC recommendations for 2019 are that, in children aged 6 months through 8 years who need two doses, start early so that you can achieve both doses before influenza season (MMWR 2019 Aug 23;68[3]:1-21).In older children and adults, who need only a single dose, early vaccination (August and early September) may lead to reduced protection late in the influenza season?
4. How can we optimize vaccine impact?
Vaccine impact refers to the affect on a population level and not at an individual level. Meagan C. Fitzpatrick, PhD, from the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, evaluated the benefits of our moderately effective influenza vaccines (VE 40%-60%) to the population beyond those who are vaccinated. Her conclusions were that even a modestly effective vaccine prevents 21 million cases of influenza, 129,000 hospitalizations, and 62,000 deaths. And that two-thirds of the deaths prevented are from herd benefit (or indirect effects). Although both coverage and vaccine effectiveness are important, she reported that population impact was most sensitive to coverage, compared with vaccine effectiveness. Dr. Fitzpatrick found that targeting school-age children 6-19 years of age and adults 30-39 years of age maximizes the public health benefits (herd effects) of influenza vaccine. In 2018 season, influenza coverage was 63% for at least one dose in children aged 6 months through 17 years and 45% in adults aged 18 years and older; in the two target age groups 5-17 and 30-39 years, coverage was 59% and approximately 35%, respectively (ID Week; Session 939).
Clearly, even our modestly effective influenza vaccines have significant public health benefit in protecting the U.S. populations from serious disease and death. Efforts to increase vaccine uptake in school-age children, both those with and without comorbidity, and the 30- to 39-year-old adult cohort would likely further reduce the burden of serious disease from influenza.
In summary, despite a vaccine that is only moderately effective, there is clear evidence to support current recommendations of universal immunization beginning at 6 months of age. Delaying until October 1 is a good idea only if the same number of individuals will receive influenza vaccine, otherwise the hypothetical benefit is lost.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and is senior attending physician, Boston Medical Center. Dr. Pelton has investigator-initiated research awards to Boston Medical Center from Pfizer and Merck Vaccines. He also received honorarium as an advisory board member, participation in symposium and consultation from Seqirus and Merck Vaccine, Pfizer, and Sanofi Pasteur. Email him at [email protected].
ID Week, the annual meeting of the Infectious Disease Society of America, provided valuable insights into past season’s endemic influenza burden and the effectiveness of prevention strategies. Each year, there are from 9million to 49 million influenza cases in the United States, 140,000-960,000 hospitalized cases, and 12,000-70,000 deaths directly attributable to influenza infection. The burden disproportionately falls on infants and adults 65 years of age and older; 11,000-48,000 children are hospitalized, and as many as several hundred children may die from influenza and related complications. School age children (aged 5-19 years) and adults (aged 30-39 years) are a major part of the transmission cycle. Influenza vaccine underlies the prevention strategy for limiting the burden of disease in U.S. populations. ID Week provided new insights into critical questions about influenza vaccines.
1. What is the effectiveness of influenza vaccine against severe disease (hospitalization) in children? Does it vary by age? By type or subtype?
Angela P. Campbell, MD, MPH, of the Centers for Disease Control and Prevention, and associates presented data on influenza vaccine effectiveness from the New Vaccine Surveillance Network in children for the 2016-2017 and 2017-2018 season (ID Week session 99; Abstract 899). During both 2016-2017 and 2017-2018, H3N2 was the dominant virus and influenza B represented about one-third of cases, and H1N1 was a greater percentage of cases in 2017-2018. Influenza positivity among children younger than 18 years of age admitted to hospital with respiratory disease was 14% among unvaccinated and 8% among vaccinated children; effectiveness again hospitalization was 50%. Vaccine effectiveness (VE) was not statistically different between children younger than 8 years of age and those older that 8 years but did differ by vaccine type. VE was 76% against H1N1 disease, 59% again B disease, and only 33% against H3N2 disease.
Clearly, vaccination with influenza vaccine prevents serious respiratory disease. However, the impact of vaccine will vary by season and by which influenza stains are circulating in the community. The authors concluded that further understanding of the lower VE against H3N2 disease is needed.
2. Does the priming dose of influenza vaccine improve vaccine effectiveness?
Current recommendations call for a two-dose series for influenza vaccine in children aged 6 months through 8 years who have not had prior influenza vaccine. The recommendation is based on evidence demonstrating higher antibody responses in children receiving two doses, compared with a single dose. Using data from the U.S. Influenza Vaccine Effectiveness Network, Jessie R. Chung, MPH, of the CDC, and associates compared VE in children younger than 2 years receiving two doses in the first year of flu immunization (fully immunized), compared with those who received only one dose (partially immunized) (ID Week session 99; Abstract 900). VE was 53% for fully immunized and 23% for partially immunized children. Receipt of a single dose did not provide statistically significant protection against influenza. Surprisingly (to me), of 5,355 children aged 6 months to less than 2 years with no prior influenza vaccine, 1,870 (35%) received only one dose in the season.
The data strongly support the current recommendations for a priming dose, especially in young children, in the first season of influenza vaccine and warrants increased efforts to increase the update of second doses during the season. Hopefully we can do better in 2019!
3. Should we wait to vaccinate with influenza vaccine?
Some evidence suggests that waning immunity to influenza vaccine, primarily in those aged 65 years and older, may explain increased disease activity toward the end of influenza season. Other explanations include increasing viral diversity throughout the season, resulting in reduced effectiveness. Do such concerns warrant delaying immunization? The onset and peak of influenza season varies by year; in October 2019, 3% of tests performed on patients with respiratory illness were influenza positive. The trade-offs for delaying immunization until October are the unpredictability of onset of influenza season, the requirement for two doses in infants, the need for 2 weeks to achieve peak antibody concentrations, and the potential that fewer individuals will be vaccinated. Kathy Neuzil, MD, MPH, from the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, reviewed recent modeling (for adults aged 65 years and older) and reported that delaying vaccine programs until October is associated with greater burden of hospitalization if 14% fewer individuals (who would be vaccinated in August/September) are vaccinated (ID Week; Session 940).
In response to these concerns, the CDC recommendations for 2019 are that, in children aged 6 months through 8 years who need two doses, start early so that you can achieve both doses before influenza season (MMWR 2019 Aug 23;68[3]:1-21).In older children and adults, who need only a single dose, early vaccination (August and early September) may lead to reduced protection late in the influenza season?
4. How can we optimize vaccine impact?
Vaccine impact refers to the affect on a population level and not at an individual level. Meagan C. Fitzpatrick, PhD, from the Center for Vaccine Development and Global Health, University of Maryland School of Medicine, evaluated the benefits of our moderately effective influenza vaccines (VE 40%-60%) to the population beyond those who are vaccinated. Her conclusions were that even a modestly effective vaccine prevents 21 million cases of influenza, 129,000 hospitalizations, and 62,000 deaths. And that two-thirds of the deaths prevented are from herd benefit (or indirect effects). Although both coverage and vaccine effectiveness are important, she reported that population impact was most sensitive to coverage, compared with vaccine effectiveness. Dr. Fitzpatrick found that targeting school-age children 6-19 years of age and adults 30-39 years of age maximizes the public health benefits (herd effects) of influenza vaccine. In 2018 season, influenza coverage was 63% for at least one dose in children aged 6 months through 17 years and 45% in adults aged 18 years and older; in the two target age groups 5-17 and 30-39 years, coverage was 59% and approximately 35%, respectively (ID Week; Session 939).
Clearly, even our modestly effective influenza vaccines have significant public health benefit in protecting the U.S. populations from serious disease and death. Efforts to increase vaccine uptake in school-age children, both those with and without comorbidity, and the 30- to 39-year-old adult cohort would likely further reduce the burden of serious disease from influenza.
In summary, despite a vaccine that is only moderately effective, there is clear evidence to support current recommendations of universal immunization beginning at 6 months of age. Delaying until October 1 is a good idea only if the same number of individuals will receive influenza vaccine, otherwise the hypothetical benefit is lost.
Dr. Pelton is professor of pediatrics and epidemiology at Boston University schools of medicine and public health and is senior attending physician, Boston Medical Center. Dr. Pelton has investigator-initiated research awards to Boston Medical Center from Pfizer and Merck Vaccines. He also received honorarium as an advisory board member, participation in symposium and consultation from Seqirus and Merck Vaccine, Pfizer, and Sanofi Pasteur. Email him at [email protected].
Sixty-five roses
Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.
My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.
away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”
Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).
Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).
Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.
This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.
My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.
I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*
Oh boy. I had to go sit in my office, turn out the lights, and cry.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.
Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.
My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.
away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”
Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).
Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).
Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.
This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.
My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.
I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*
Oh boy. I had to go sit in my office, turn out the lights, and cry.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.
Like many of you, my wife and I took the DNA plunge for fun and spit in the cup. She is genetically perfect, but I, however, am a carrier for alpha-1 anti-trypsin deficiency, hemochromatosis, and like 1 in 19 Irish people, cystic fibrosis. Plus, I was in the top 20% for Neanderthal genes.
My Y chromosome had traveled to the United States from Europe, where it had spent several hundred years in Ireland (in the house of Neal); wandering to Ireland from the Middle East, and originating in Siberia! Fascinating stuff.
away. It is hypothesized that the very-high-frequency deleterious genes have a survival advantage in the heterozygous state, coined the “heterozygote advantage.”
Alpha-1 antitrypsin deficiency allows the body to concentrate an inflammatory response in the lungs and liver, perhaps providing protection against tuberculosis (Am J Respir Crit Care Med. 2006 May 15;173[10]:1072-7).
Hemochromatosis allows for increased iron absorption attributable to decreased iron in a grain-based diet, and facilitates thyroid-stimulating hormone release in cold environments (Am J Phys Anthropol. 2016 May;160[1]:86-101).
Cystic fibrosis carriers are more resistant to diarrheal illness, particularly cholera and typhoid fever since they have only one exudative chloride channel to switch on. Their sputum is also thicker, interfering with microdroplet generation and spread of the bacilli to others.
This topic and learning of my CF carrier status bring to mind one of my patients. When doing skin exams, I sometimes ask patients about elaborate tattoos (not the obvious youthful misadventures). “Nice ink” I will say, and I wait and see if they want to elaborate. This particular patient was enthusiastic and explained that the elaborate floral design with roses on his right leg was in memory of his daughter. I asked what had happened, expecting a tragic car wreck, or perhaps cancer or a drug overdose. He cheerfully explained she had died of cystic fibrosis at age 21, a year after a lung transplant.
My eyes started to water. My patient was upbeat and said she had lived with gusto and survived long enough to buy him a triple gin and tonic at bar. She had always had a bright outlook, despite her debilitating and eventually fatal disease.
I had to ask more about the memorial tattoo. He explained that her initials were linked with his at the bottom of the bouquet of many, many roses. “Why roses?” I asked. “Well,” he said, “when she was little, she could not pronounce cystic fibrosis, so she always said, ‘My daddy says I have 65 roses.’ ”*
Oh boy. I had to go sit in my office, turn out the lights, and cry.
Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. Write to him at [email protected].
* This is in fact, what many children with the disease call it, and is the symbol of the Cystic Fibrosis Foundation, a story originating in 1965, when a 4-year-old with cystic fibrosis asked his mother about “65 Roses” after he heard her talking on the phone raising funds for research.
Psychodiagnostic testing services: The elusive quest for clinicians
Assessment psychologists should be colocated in specialty practices
Imagine the clinical care consequences if patients seen in specialty or primary care practices did not have ready access to laboratory, other medical tests, and/or consultative services deemed critical to quickly establishing diagnostic status and the development of an appropriate treatment plan. For instance, what would be the implications if a dentistry practice did not employ a dental hygienist; an otolaryngology group was not staffed with an audiologist; or a gastroenterology practice had no one available for digestive/nutritional consultation support.
Consider a neurologist who suspects that a patient has a potentially life-threatening brain condition, but the patient has to wait months for brain imaging or – even worse – is tasked to find their own provider for this diagnostic test only to be told that the neuroimaging service does not take their insurance and/or there are no available appointments for several months.
Situations of this kind would not be – and should not be – tolerated by medical professionals or their patients.
A common “real-world” scenario: After evaluation, a psychiatrist needs clarification regarding a possible subtle psychotic process, or, in another instance, suspects that there is an early degenerative cognitive change underlying recent changes in mood and personality. However, the psychiatrist has no dependable access to an assessment psychologist to assist in cases of this kind.
Patients are frequently told by psychiatrists and other physicians that they should have psychodiagnostic testing to arrive at a clearer picture of their clinical status and treatment needs. However, most medical practices, in particular, psychiatry, pediatrics, neurology, and neurosurgery, who see substantial numbers of patients who could benefit from testing, do not employ psychologists. When they do, many do not possess the requisite assessment skills to address the reason(s) for referral.
If the patient needing testing services is fortunate enough, he/she is referred to a well-trained psychologist within commuting distance who takes the patient’s insurance and is able to set up a timely appointment – an unlikely set of circumstances in today’s health care environment.
Some state psychological associations allow for a “matching service” of sorts in the form of announcements in the organization’s listserv, which reviews the referral and includes a back channel for psychologists to contact the patient regarding their availability for testing.
Over the past 2 decades, significant advancements have been made in the integration of primary and mental health care. Those need to continue to include colocating assessment psychologists in medical specialty practices, such as psychiatry, which make frequent referrals for psychodiagnostic testing or would like to but have no place to turn.
Dr. Pollak is affiliated with the Seacoast Mental Health Center in Portsmouth, N.H.
Assessment psychologists should be colocated in specialty practices
Assessment psychologists should be colocated in specialty practices
Imagine the clinical care consequences if patients seen in specialty or primary care practices did not have ready access to laboratory, other medical tests, and/or consultative services deemed critical to quickly establishing diagnostic status and the development of an appropriate treatment plan. For instance, what would be the implications if a dentistry practice did not employ a dental hygienist; an otolaryngology group was not staffed with an audiologist; or a gastroenterology practice had no one available for digestive/nutritional consultation support.
Consider a neurologist who suspects that a patient has a potentially life-threatening brain condition, but the patient has to wait months for brain imaging or – even worse – is tasked to find their own provider for this diagnostic test only to be told that the neuroimaging service does not take their insurance and/or there are no available appointments for several months.
Situations of this kind would not be – and should not be – tolerated by medical professionals or their patients.
A common “real-world” scenario: After evaluation, a psychiatrist needs clarification regarding a possible subtle psychotic process, or, in another instance, suspects that there is an early degenerative cognitive change underlying recent changes in mood and personality. However, the psychiatrist has no dependable access to an assessment psychologist to assist in cases of this kind.
Patients are frequently told by psychiatrists and other physicians that they should have psychodiagnostic testing to arrive at a clearer picture of their clinical status and treatment needs. However, most medical practices, in particular, psychiatry, pediatrics, neurology, and neurosurgery, who see substantial numbers of patients who could benefit from testing, do not employ psychologists. When they do, many do not possess the requisite assessment skills to address the reason(s) for referral.
If the patient needing testing services is fortunate enough, he/she is referred to a well-trained psychologist within commuting distance who takes the patient’s insurance and is able to set up a timely appointment – an unlikely set of circumstances in today’s health care environment.
Some state psychological associations allow for a “matching service” of sorts in the form of announcements in the organization’s listserv, which reviews the referral and includes a back channel for psychologists to contact the patient regarding their availability for testing.
Over the past 2 decades, significant advancements have been made in the integration of primary and mental health care. Those need to continue to include colocating assessment psychologists in medical specialty practices, such as psychiatry, which make frequent referrals for psychodiagnostic testing or would like to but have no place to turn.
Dr. Pollak is affiliated with the Seacoast Mental Health Center in Portsmouth, N.H.
Imagine the clinical care consequences if patients seen in specialty or primary care practices did not have ready access to laboratory, other medical tests, and/or consultative services deemed critical to quickly establishing diagnostic status and the development of an appropriate treatment plan. For instance, what would be the implications if a dentistry practice did not employ a dental hygienist; an otolaryngology group was not staffed with an audiologist; or a gastroenterology practice had no one available for digestive/nutritional consultation support.
Consider a neurologist who suspects that a patient has a potentially life-threatening brain condition, but the patient has to wait months for brain imaging or – even worse – is tasked to find their own provider for this diagnostic test only to be told that the neuroimaging service does not take their insurance and/or there are no available appointments for several months.
Situations of this kind would not be – and should not be – tolerated by medical professionals or their patients.
A common “real-world” scenario: After evaluation, a psychiatrist needs clarification regarding a possible subtle psychotic process, or, in another instance, suspects that there is an early degenerative cognitive change underlying recent changes in mood and personality. However, the psychiatrist has no dependable access to an assessment psychologist to assist in cases of this kind.
Patients are frequently told by psychiatrists and other physicians that they should have psychodiagnostic testing to arrive at a clearer picture of their clinical status and treatment needs. However, most medical practices, in particular, psychiatry, pediatrics, neurology, and neurosurgery, who see substantial numbers of patients who could benefit from testing, do not employ psychologists. When they do, many do not possess the requisite assessment skills to address the reason(s) for referral.
If the patient needing testing services is fortunate enough, he/she is referred to a well-trained psychologist within commuting distance who takes the patient’s insurance and is able to set up a timely appointment – an unlikely set of circumstances in today’s health care environment.
Some state psychological associations allow for a “matching service” of sorts in the form of announcements in the organization’s listserv, which reviews the referral and includes a back channel for psychologists to contact the patient regarding their availability for testing.
Over the past 2 decades, significant advancements have been made in the integration of primary and mental health care. Those need to continue to include colocating assessment psychologists in medical specialty practices, such as psychiatry, which make frequent referrals for psychodiagnostic testing or would like to but have no place to turn.
Dr. Pollak is affiliated with the Seacoast Mental Health Center in Portsmouth, N.H.
Primary CNS lymphoma: R-CHOP hits back
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma solely confined to the CNS. The majority of PCNSL histologically presents as diffuse large B-cell lymphoma (DLBCL). However, outcomes in these patients are notably inferior, compared with nodal or other extranodal DLBCL. In order to achieve long-term progression-free survival, high-dose methotrexate (HD-MTX)–based chemotherapy followed by consolidation is needed. However, this treatment is associated with high toxicity burden and it is restricted to a select patient population – the young and fit – and requires administration at specialized hematological centers.
In the 1990s, the conventional DLBCL treatment regimen with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was tested in PCNSL patients. The results were rather disappointing. The addition of CHOP to whole brain radiation or HD-MTX could not improve survival.1-3 The reason for CHOP failure was poor CNS penetration of doxorubicin and cyclophosphamide because of their high molecular weight. Consequently, it was concluded that there is no role for CHOP-like chemotherapy in the treatment of PCNSL.4
But is this really the case? Twenty years later, this traditional view has been challenged by Andres J.M. Ferreri, MD, and colleagues in the INGRID trial.5 Dr. Ferreri presented findings from the trial at the International Conference on Malignant Lymphoma in Lugano, Switzerland, which was greeted with much excitement.6
INGRID is a phase 2 trial conducted on patients with refractory/relapsed PCNSL. It consisted of a CHOP plus rituximab (R-CHOP) regimen, which was upgraded by engineered tumor necrosis factor–alpha (TNF-alpha). The idea was to enhance the blood-brain barrier (BBB) permeability and consequently improve the efficacy of R-CHOP in PCNSL. The use of human TNF-alpha is limited by relevant toxicities. In order to avoid that, a fusion of human TNF-alpha and CNGRCG peptide (called NGR-TNF) was developed.
CNGRCG peptide is a ligand of CD13, an aminopeptidase that is expressed almost exclusively on tumor blood vessels. Preclinical data showed that binding of CNGRCG to CD13 results in targeted – local, not systemic – delivery of TNF-alpha to the tumor blood vessels. Consequently, TNF-alpha led to increased vascular permeability in tumor tissue and enabled higher penetration of chemotherapeutic agents.7,8
Altogether, 12 heavily pretreated PCNSL patients were included in the INGRID trial. Seven patients had two or more previous treatment regimens. Within this trial, patients received R-CHOP with NGR-TNF (0.8 mcg/m2) applied 2 hours prior to R-CHOP. The great majority of grade 3/4 adverse events were hematological toxicities. Importantly, no neurological side effects of any grade occurred.
The primary aim of this study was to investigate the CD13 expression on tumor tissue and provide a proof of concept for the use of NGR-TNF/R-CHOP. Indeed, CD13 expression was observed on tumor vessels in all patients. Consequently, increased BBB permeability in tumor tissue after NGR-TNF infusion was observed using dynamic contrast-enhanced MRI and by brain scintigraphy (SPECT). This was assessed 1 day after NGR-TNF/R-CHOP treatment. More importantly, this effect on BBB seems to be sustained because it was also observed after the last cycle of NGR-TNF/R-CHOP. The fact that there was no change of drug concentrations of R-CHOP components in plasma or cerebrospinal fluid suggests that the effect of NGR-TNF is restricted to tumor vessels.
The authors also reported preliminary results regarding response rates to NGR-TNF/R-CHOP. The overall response rate was 75%. Of note, six patients achieved complete remission and one patient achieved a partial remission. The median duration of response was 10 months (range, 7-14 months), and nine patients were able to proceed to consolidation treatment.
These preliminary results are encouraging and open a new window for the treatment strategies in PCNSL patients. NGR-TNF/R-CHOP treatment induced responses in 75% of these heavily pretreated patients. The low toxicity profile and feasibility of this regimen could allow clinicians to carry out this treatment approach in outpatient settings, as well as in older and comorbid patients. Extensive supportive therapy – such as intensive hydration or leucovorin-rescue by HD-MTX – is not needed.
These results will need to be confirmed through testing in a larger patient population. Dr. Ferreri and colleagues are currently conducting the extended phase of this study and aim to recruit 28 patients. If they report positive results from that study, evaluation of NGR-TNF/R-CHOP as a first-line treatment of PCNSL seems to be the next reasonable step.
Dr. Zeremski and Dr. Fischer are both in the department of hematology/oncology and affiliated with the Health Campus Immunology, Infectiology and Inflammation at Otto-von-Guericke University Magdeburg (Germany). Dr. Fischer is a member of the editorial advisory board of Hematology News. The authors reported having no conflicts of interest.
References
1. J Clin Oncol. 1996;14:556-64.
2. Cancer. 2000;89:1359-70.
3. J Neurooncol. 1996;30:257-65.
4. Guidelines on the diagnosis and management of adult patients with primary CNS lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL). British Society for Haematology/British Committee for Standards in Haematology; HO/016, 2009.
5. Blood. 2019;134:252-62.
6. Hematol Oncol. 2019; 37:159.
7. BioDrugs. 2013;27:591-603.
8. J Clin Invest. 2002;110:475-82.
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma solely confined to the CNS. The majority of PCNSL histologically presents as diffuse large B-cell lymphoma (DLBCL). However, outcomes in these patients are notably inferior, compared with nodal or other extranodal DLBCL. In order to achieve long-term progression-free survival, high-dose methotrexate (HD-MTX)–based chemotherapy followed by consolidation is needed. However, this treatment is associated with high toxicity burden and it is restricted to a select patient population – the young and fit – and requires administration at specialized hematological centers.
In the 1990s, the conventional DLBCL treatment regimen with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was tested in PCNSL patients. The results were rather disappointing. The addition of CHOP to whole brain radiation or HD-MTX could not improve survival.1-3 The reason for CHOP failure was poor CNS penetration of doxorubicin and cyclophosphamide because of their high molecular weight. Consequently, it was concluded that there is no role for CHOP-like chemotherapy in the treatment of PCNSL.4
But is this really the case? Twenty years later, this traditional view has been challenged by Andres J.M. Ferreri, MD, and colleagues in the INGRID trial.5 Dr. Ferreri presented findings from the trial at the International Conference on Malignant Lymphoma in Lugano, Switzerland, which was greeted with much excitement.6
INGRID is a phase 2 trial conducted on patients with refractory/relapsed PCNSL. It consisted of a CHOP plus rituximab (R-CHOP) regimen, which was upgraded by engineered tumor necrosis factor–alpha (TNF-alpha). The idea was to enhance the blood-brain barrier (BBB) permeability and consequently improve the efficacy of R-CHOP in PCNSL. The use of human TNF-alpha is limited by relevant toxicities. In order to avoid that, a fusion of human TNF-alpha and CNGRCG peptide (called NGR-TNF) was developed.
CNGRCG peptide is a ligand of CD13, an aminopeptidase that is expressed almost exclusively on tumor blood vessels. Preclinical data showed that binding of CNGRCG to CD13 results in targeted – local, not systemic – delivery of TNF-alpha to the tumor blood vessels. Consequently, TNF-alpha led to increased vascular permeability in tumor tissue and enabled higher penetration of chemotherapeutic agents.7,8
Altogether, 12 heavily pretreated PCNSL patients were included in the INGRID trial. Seven patients had two or more previous treatment regimens. Within this trial, patients received R-CHOP with NGR-TNF (0.8 mcg/m2) applied 2 hours prior to R-CHOP. The great majority of grade 3/4 adverse events were hematological toxicities. Importantly, no neurological side effects of any grade occurred.
The primary aim of this study was to investigate the CD13 expression on tumor tissue and provide a proof of concept for the use of NGR-TNF/R-CHOP. Indeed, CD13 expression was observed on tumor vessels in all patients. Consequently, increased BBB permeability in tumor tissue after NGR-TNF infusion was observed using dynamic contrast-enhanced MRI and by brain scintigraphy (SPECT). This was assessed 1 day after NGR-TNF/R-CHOP treatment. More importantly, this effect on BBB seems to be sustained because it was also observed after the last cycle of NGR-TNF/R-CHOP. The fact that there was no change of drug concentrations of R-CHOP components in plasma or cerebrospinal fluid suggests that the effect of NGR-TNF is restricted to tumor vessels.
The authors also reported preliminary results regarding response rates to NGR-TNF/R-CHOP. The overall response rate was 75%. Of note, six patients achieved complete remission and one patient achieved a partial remission. The median duration of response was 10 months (range, 7-14 months), and nine patients were able to proceed to consolidation treatment.
These preliminary results are encouraging and open a new window for the treatment strategies in PCNSL patients. NGR-TNF/R-CHOP treatment induced responses in 75% of these heavily pretreated patients. The low toxicity profile and feasibility of this regimen could allow clinicians to carry out this treatment approach in outpatient settings, as well as in older and comorbid patients. Extensive supportive therapy – such as intensive hydration or leucovorin-rescue by HD-MTX – is not needed.
These results will need to be confirmed through testing in a larger patient population. Dr. Ferreri and colleagues are currently conducting the extended phase of this study and aim to recruit 28 patients. If they report positive results from that study, evaluation of NGR-TNF/R-CHOP as a first-line treatment of PCNSL seems to be the next reasonable step.
Dr. Zeremski and Dr. Fischer are both in the department of hematology/oncology and affiliated with the Health Campus Immunology, Infectiology and Inflammation at Otto-von-Guericke University Magdeburg (Germany). Dr. Fischer is a member of the editorial advisory board of Hematology News. The authors reported having no conflicts of interest.
References
1. J Clin Oncol. 1996;14:556-64.
2. Cancer. 2000;89:1359-70.
3. J Neurooncol. 1996;30:257-65.
4. Guidelines on the diagnosis and management of adult patients with primary CNS lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL). British Society for Haematology/British Committee for Standards in Haematology; HO/016, 2009.
5. Blood. 2019;134:252-62.
6. Hematol Oncol. 2019; 37:159.
7. BioDrugs. 2013;27:591-603.
8. J Clin Invest. 2002;110:475-82.
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma solely confined to the CNS. The majority of PCNSL histologically presents as diffuse large B-cell lymphoma (DLBCL). However, outcomes in these patients are notably inferior, compared with nodal or other extranodal DLBCL. In order to achieve long-term progression-free survival, high-dose methotrexate (HD-MTX)–based chemotherapy followed by consolidation is needed. However, this treatment is associated with high toxicity burden and it is restricted to a select patient population – the young and fit – and requires administration at specialized hematological centers.
In the 1990s, the conventional DLBCL treatment regimen with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was tested in PCNSL patients. The results were rather disappointing. The addition of CHOP to whole brain radiation or HD-MTX could not improve survival.1-3 The reason for CHOP failure was poor CNS penetration of doxorubicin and cyclophosphamide because of their high molecular weight. Consequently, it was concluded that there is no role for CHOP-like chemotherapy in the treatment of PCNSL.4
But is this really the case? Twenty years later, this traditional view has been challenged by Andres J.M. Ferreri, MD, and colleagues in the INGRID trial.5 Dr. Ferreri presented findings from the trial at the International Conference on Malignant Lymphoma in Lugano, Switzerland, which was greeted with much excitement.6
INGRID is a phase 2 trial conducted on patients with refractory/relapsed PCNSL. It consisted of a CHOP plus rituximab (R-CHOP) regimen, which was upgraded by engineered tumor necrosis factor–alpha (TNF-alpha). The idea was to enhance the blood-brain barrier (BBB) permeability and consequently improve the efficacy of R-CHOP in PCNSL. The use of human TNF-alpha is limited by relevant toxicities. In order to avoid that, a fusion of human TNF-alpha and CNGRCG peptide (called NGR-TNF) was developed.
CNGRCG peptide is a ligand of CD13, an aminopeptidase that is expressed almost exclusively on tumor blood vessels. Preclinical data showed that binding of CNGRCG to CD13 results in targeted – local, not systemic – delivery of TNF-alpha to the tumor blood vessels. Consequently, TNF-alpha led to increased vascular permeability in tumor tissue and enabled higher penetration of chemotherapeutic agents.7,8
Altogether, 12 heavily pretreated PCNSL patients were included in the INGRID trial. Seven patients had two or more previous treatment regimens. Within this trial, patients received R-CHOP with NGR-TNF (0.8 mcg/m2) applied 2 hours prior to R-CHOP. The great majority of grade 3/4 adverse events were hematological toxicities. Importantly, no neurological side effects of any grade occurred.
The primary aim of this study was to investigate the CD13 expression on tumor tissue and provide a proof of concept for the use of NGR-TNF/R-CHOP. Indeed, CD13 expression was observed on tumor vessels in all patients. Consequently, increased BBB permeability in tumor tissue after NGR-TNF infusion was observed using dynamic contrast-enhanced MRI and by brain scintigraphy (SPECT). This was assessed 1 day after NGR-TNF/R-CHOP treatment. More importantly, this effect on BBB seems to be sustained because it was also observed after the last cycle of NGR-TNF/R-CHOP. The fact that there was no change of drug concentrations of R-CHOP components in plasma or cerebrospinal fluid suggests that the effect of NGR-TNF is restricted to tumor vessels.
The authors also reported preliminary results regarding response rates to NGR-TNF/R-CHOP. The overall response rate was 75%. Of note, six patients achieved complete remission and one patient achieved a partial remission. The median duration of response was 10 months (range, 7-14 months), and nine patients were able to proceed to consolidation treatment.
These preliminary results are encouraging and open a new window for the treatment strategies in PCNSL patients. NGR-TNF/R-CHOP treatment induced responses in 75% of these heavily pretreated patients. The low toxicity profile and feasibility of this regimen could allow clinicians to carry out this treatment approach in outpatient settings, as well as in older and comorbid patients. Extensive supportive therapy – such as intensive hydration or leucovorin-rescue by HD-MTX – is not needed.
These results will need to be confirmed through testing in a larger patient population. Dr. Ferreri and colleagues are currently conducting the extended phase of this study and aim to recruit 28 patients. If they report positive results from that study, evaluation of NGR-TNF/R-CHOP as a first-line treatment of PCNSL seems to be the next reasonable step.
Dr. Zeremski and Dr. Fischer are both in the department of hematology/oncology and affiliated with the Health Campus Immunology, Infectiology and Inflammation at Otto-von-Guericke University Magdeburg (Germany). Dr. Fischer is a member of the editorial advisory board of Hematology News. The authors reported having no conflicts of interest.
References
1. J Clin Oncol. 1996;14:556-64.
2. Cancer. 2000;89:1359-70.
3. J Neurooncol. 1996;30:257-65.
4. Guidelines on the diagnosis and management of adult patients with primary CNS lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL). British Society for Haematology/British Committee for Standards in Haematology; HO/016, 2009.
5. Blood. 2019;134:252-62.
6. Hematol Oncol. 2019; 37:159.
7. BioDrugs. 2013;27:591-603.
8. J Clin Invest. 2002;110:475-82.
Psilocybin research at Johns Hopkins
A new center opens to study novel treatment uses for psychedelics
Psychiatry Grand Rounds started on Monday, Oct. 7, 2019, as they do every Monday at Johns Hopkins, with the department chair interviewing a patient.
The patient told James Potash, MD, that he had suffered with depression for many years and that medications were only a partial fix. His participation in a psilocybin trial at Johns Hopkins in Baltimore was different, and 3 months after the second, and final, treatment, he felt remarkably better. The treatment had quieted the self-deprecating script that had looped through his thoughts for years. “It was nothing like what I was expecting,” the patient said. “I didn’t feel out of control. And now I’m not fighting with myself all day.”
Grand Rounds at Hopkins are different from those at other institutions in that the rounds are given by departments’ full-time faculty members; psychiatrists from other institutions are invited to come speak at other times during the week. But Grand Rounds are reserved for the faculty to present their own research. The patient interview was followed by a lecture by Roland Griffiths, PhD, on “Psilocybin: A potentially promising treatment for depression.” Dr. Griffiths has been studying the effects of psychedelic drugs for the past 40 years; he’s been at Hopkins since 1972. The Grand Rounds presentation came just weeks after it was announced that Dr. Griffiths would be heading the Johns Hopkins Center for Psychedelic & Consciousness Research, funded with $17 million in private donations.
Dr. Griffiths began by talking about the history of psychedelic drug research and the fact that research had been dormant for several decades. “There was – and still is – concern about potential adverse reactions, including panic reactions and the possibility of precipitating psychosis,” he said.
Originally, he conducted several studies in healthy volunteers with no history of psychedelic use. Participants had one or more day-long sessions with staff members who would then serve as monitors when psilocybin was administered; these preliminary meetings were designed to build trust and rapport with the team and to decrease the risk of adverse reactions. On session days when psilocybin was administered, participants were told to eat a low-fat breakfast and then were given a high dose of psilocybin in a capsule. The next 6 hours were spent with the volunteer lying on a couch with an eye mask, headphones with soft music, and two monitors in the room. “The room is decorated like a living room. We created a container for people to explore their inner experience.”
Dr. Griffiths talked about the experiences people reported.
“There were large increases in personally meaningful and insight-type experiences. People reported a sense of unity and interconnectedness of all things, accompanied by a sense of preciousness or reverence, and by the sense that ... the experience was more real or true than everyday waking consciousness. Although the acute effects of psilocybin resolved by the end of the session day, the memories remain and people reported enduring changes in mood, attitude, and behavior.”
The data were remarkable. One month after these high-dose psilocybin sessions, 78% of the volunteers rated the experience as among the top five most personally meaningful experiences of their lives, 94% said they had an increased sense of well-being with improved life satisfaction, and nearly 90% endorsed positive behavior change. Six months after the last session, participants still endorsed having more positive relationships, feeling more love, tolerance, empathy and compassion, friends, family members, and others. Family members and work colleagues who were interviewed noted these positive changes as well.
At this point in Grand Rounds, I was ready to volunteer. My best estimate (tongue in cheek, with no corroboration) is that about half of the audience was waiting on free psilocybin samples, while the other half was remembering Timothy Leary, PhD, bad trips, and psychosis. “We’ve been down this road before,” the gentleman next to me commented.
Dr. Griffiths went on to talk about trials of psilocybin in clinical populations. In one study, the effects of psilocybin were examined in cancer patients with depression and anxiety. Of the 51 cancer patients, half previously had been treated with psychotropic medications before coming to the study. This randomized, double-blind crossover study compared high-dose psilocybin with an extremely low dose of psilocybin used as the placebo.
Another study looked at patients with major depression who, like the patient interviewed, had not had full resolution of symptoms with conventional antidepressants. Of the 24 participants in that group, 69% reported clinically significant improvement 12 weeks after the treatment. Just over half of participants reported a full remission to normal.
Dr. Griffiths ended by concluding that the positive experiences people have with psilocybin are associated with “enduring positive trait changes in attitudes, mood and behavior, spirituality, and altruism ... and that such experiences are now amenable to systematic prospective scientific study.”
J. Raymond DePaulo, MD, chair of the National Network of Depression Centers and former chair of psychiatry at Johns Hopkins, noted that he used to be skeptical. He has been impressed that Dr. Griffiths has listened to criticism and addressed concerns others have raised. “When it was suggested that this was the result of delirium, he started giving people cognitive tests while they were using psilocybin and he showed it wasn’t the case.”
“I have always objected to words like ‘psychedelic’ and ‘hallucinogen,’ ” said Dr. DePaulo. “They are confusing and inaccurate. No one takes these medications because they want to hallucinate. They take them to change their mood. That said, I am thrilled that we are on the precipice of being able to use this to treat depression.”
Since 1999, the Johns Hopkins Psilocybin Research Project has conducted more than 700 sessions with 369 participants. When might psilocybin be available to patients outside of a research protocol? Two companies have obtained approval from the Food and Drug Administration to initiate registration in trials for treatment of depression. Dr. Griffiths estimates that it could be another 5 years before psilocybin will be available for medical use.
The new center with its generous funding will allow for more studies with more patient populations. The center’s projects will look at using psilocybin as a treatment for opioid use disorder, comorbid depression and alcohol use disorder, anorexia nervosa, depression in Alzheimer’s disease, posttreatment Lyme disease syndrome, and PTSD.
Scott Aaronson, MD, is a mood disorder expert and director of clinical research at the Sheppard Pratt Health System in Towson/Baltimore. Dr. Aaronson, who also studies psilocybin as a treatment for depression, noted: “The problem with the development of psychedelics is that we are not really prepared to capture the improvement we see with their use, as the main changes are not in the classic markers of depression like the Montgomery-Åsberg or the Hamilton Depression rating scales, but [rather] in the patient’s perception of who they are, how they fit in with the world, and what is most important. We need to develop ways to capture those critical changes and work with the FDA to develop an entirely new vision of what constitutes improvement in psychiatric illness. My overall take is that it is a terrific time to specialize in treatment-resistant mood disorders!”
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.
A new center opens to study novel treatment uses for psychedelics
A new center opens to study novel treatment uses for psychedelics
Psychiatry Grand Rounds started on Monday, Oct. 7, 2019, as they do every Monday at Johns Hopkins, with the department chair interviewing a patient.
The patient told James Potash, MD, that he had suffered with depression for many years and that medications were only a partial fix. His participation in a psilocybin trial at Johns Hopkins in Baltimore was different, and 3 months after the second, and final, treatment, he felt remarkably better. The treatment had quieted the self-deprecating script that had looped through his thoughts for years. “It was nothing like what I was expecting,” the patient said. “I didn’t feel out of control. And now I’m not fighting with myself all day.”
Grand Rounds at Hopkins are different from those at other institutions in that the rounds are given by departments’ full-time faculty members; psychiatrists from other institutions are invited to come speak at other times during the week. But Grand Rounds are reserved for the faculty to present their own research. The patient interview was followed by a lecture by Roland Griffiths, PhD, on “Psilocybin: A potentially promising treatment for depression.” Dr. Griffiths has been studying the effects of psychedelic drugs for the past 40 years; he’s been at Hopkins since 1972. The Grand Rounds presentation came just weeks after it was announced that Dr. Griffiths would be heading the Johns Hopkins Center for Psychedelic & Consciousness Research, funded with $17 million in private donations.
Dr. Griffiths began by talking about the history of psychedelic drug research and the fact that research had been dormant for several decades. “There was – and still is – concern about potential adverse reactions, including panic reactions and the possibility of precipitating psychosis,” he said.
Originally, he conducted several studies in healthy volunteers with no history of psychedelic use. Participants had one or more day-long sessions with staff members who would then serve as monitors when psilocybin was administered; these preliminary meetings were designed to build trust and rapport with the team and to decrease the risk of adverse reactions. On session days when psilocybin was administered, participants were told to eat a low-fat breakfast and then were given a high dose of psilocybin in a capsule. The next 6 hours were spent with the volunteer lying on a couch with an eye mask, headphones with soft music, and two monitors in the room. “The room is decorated like a living room. We created a container for people to explore their inner experience.”
Dr. Griffiths talked about the experiences people reported.
“There were large increases in personally meaningful and insight-type experiences. People reported a sense of unity and interconnectedness of all things, accompanied by a sense of preciousness or reverence, and by the sense that ... the experience was more real or true than everyday waking consciousness. Although the acute effects of psilocybin resolved by the end of the session day, the memories remain and people reported enduring changes in mood, attitude, and behavior.”
The data were remarkable. One month after these high-dose psilocybin sessions, 78% of the volunteers rated the experience as among the top five most personally meaningful experiences of their lives, 94% said they had an increased sense of well-being with improved life satisfaction, and nearly 90% endorsed positive behavior change. Six months after the last session, participants still endorsed having more positive relationships, feeling more love, tolerance, empathy and compassion, friends, family members, and others. Family members and work colleagues who were interviewed noted these positive changes as well.
At this point in Grand Rounds, I was ready to volunteer. My best estimate (tongue in cheek, with no corroboration) is that about half of the audience was waiting on free psilocybin samples, while the other half was remembering Timothy Leary, PhD, bad trips, and psychosis. “We’ve been down this road before,” the gentleman next to me commented.
Dr. Griffiths went on to talk about trials of psilocybin in clinical populations. In one study, the effects of psilocybin were examined in cancer patients with depression and anxiety. Of the 51 cancer patients, half previously had been treated with psychotropic medications before coming to the study. This randomized, double-blind crossover study compared high-dose psilocybin with an extremely low dose of psilocybin used as the placebo.
Another study looked at patients with major depression who, like the patient interviewed, had not had full resolution of symptoms with conventional antidepressants. Of the 24 participants in that group, 69% reported clinically significant improvement 12 weeks after the treatment. Just over half of participants reported a full remission to normal.
Dr. Griffiths ended by concluding that the positive experiences people have with psilocybin are associated with “enduring positive trait changes in attitudes, mood and behavior, spirituality, and altruism ... and that such experiences are now amenable to systematic prospective scientific study.”
J. Raymond DePaulo, MD, chair of the National Network of Depression Centers and former chair of psychiatry at Johns Hopkins, noted that he used to be skeptical. He has been impressed that Dr. Griffiths has listened to criticism and addressed concerns others have raised. “When it was suggested that this was the result of delirium, he started giving people cognitive tests while they were using psilocybin and he showed it wasn’t the case.”
“I have always objected to words like ‘psychedelic’ and ‘hallucinogen,’ ” said Dr. DePaulo. “They are confusing and inaccurate. No one takes these medications because they want to hallucinate. They take them to change their mood. That said, I am thrilled that we are on the precipice of being able to use this to treat depression.”
Since 1999, the Johns Hopkins Psilocybin Research Project has conducted more than 700 sessions with 369 participants. When might psilocybin be available to patients outside of a research protocol? Two companies have obtained approval from the Food and Drug Administration to initiate registration in trials for treatment of depression. Dr. Griffiths estimates that it could be another 5 years before psilocybin will be available for medical use.
The new center with its generous funding will allow for more studies with more patient populations. The center’s projects will look at using psilocybin as a treatment for opioid use disorder, comorbid depression and alcohol use disorder, anorexia nervosa, depression in Alzheimer’s disease, posttreatment Lyme disease syndrome, and PTSD.
Scott Aaronson, MD, is a mood disorder expert and director of clinical research at the Sheppard Pratt Health System in Towson/Baltimore. Dr. Aaronson, who also studies psilocybin as a treatment for depression, noted: “The problem with the development of psychedelics is that we are not really prepared to capture the improvement we see with their use, as the main changes are not in the classic markers of depression like the Montgomery-Åsberg or the Hamilton Depression rating scales, but [rather] in the patient’s perception of who they are, how they fit in with the world, and what is most important. We need to develop ways to capture those critical changes and work with the FDA to develop an entirely new vision of what constitutes improvement in psychiatric illness. My overall take is that it is a terrific time to specialize in treatment-resistant mood disorders!”
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.
Psychiatry Grand Rounds started on Monday, Oct. 7, 2019, as they do every Monday at Johns Hopkins, with the department chair interviewing a patient.
The patient told James Potash, MD, that he had suffered with depression for many years and that medications were only a partial fix. His participation in a psilocybin trial at Johns Hopkins in Baltimore was different, and 3 months after the second, and final, treatment, he felt remarkably better. The treatment had quieted the self-deprecating script that had looped through his thoughts for years. “It was nothing like what I was expecting,” the patient said. “I didn’t feel out of control. And now I’m not fighting with myself all day.”
Grand Rounds at Hopkins are different from those at other institutions in that the rounds are given by departments’ full-time faculty members; psychiatrists from other institutions are invited to come speak at other times during the week. But Grand Rounds are reserved for the faculty to present their own research. The patient interview was followed by a lecture by Roland Griffiths, PhD, on “Psilocybin: A potentially promising treatment for depression.” Dr. Griffiths has been studying the effects of psychedelic drugs for the past 40 years; he’s been at Hopkins since 1972. The Grand Rounds presentation came just weeks after it was announced that Dr. Griffiths would be heading the Johns Hopkins Center for Psychedelic & Consciousness Research, funded with $17 million in private donations.
Dr. Griffiths began by talking about the history of psychedelic drug research and the fact that research had been dormant for several decades. “There was – and still is – concern about potential adverse reactions, including panic reactions and the possibility of precipitating psychosis,” he said.
Originally, he conducted several studies in healthy volunteers with no history of psychedelic use. Participants had one or more day-long sessions with staff members who would then serve as monitors when psilocybin was administered; these preliminary meetings were designed to build trust and rapport with the team and to decrease the risk of adverse reactions. On session days when psilocybin was administered, participants were told to eat a low-fat breakfast and then were given a high dose of psilocybin in a capsule. The next 6 hours were spent with the volunteer lying on a couch with an eye mask, headphones with soft music, and two monitors in the room. “The room is decorated like a living room. We created a container for people to explore their inner experience.”
Dr. Griffiths talked about the experiences people reported.
“There were large increases in personally meaningful and insight-type experiences. People reported a sense of unity and interconnectedness of all things, accompanied by a sense of preciousness or reverence, and by the sense that ... the experience was more real or true than everyday waking consciousness. Although the acute effects of psilocybin resolved by the end of the session day, the memories remain and people reported enduring changes in mood, attitude, and behavior.”
The data were remarkable. One month after these high-dose psilocybin sessions, 78% of the volunteers rated the experience as among the top five most personally meaningful experiences of their lives, 94% said they had an increased sense of well-being with improved life satisfaction, and nearly 90% endorsed positive behavior change. Six months after the last session, participants still endorsed having more positive relationships, feeling more love, tolerance, empathy and compassion, friends, family members, and others. Family members and work colleagues who were interviewed noted these positive changes as well.
At this point in Grand Rounds, I was ready to volunteer. My best estimate (tongue in cheek, with no corroboration) is that about half of the audience was waiting on free psilocybin samples, while the other half was remembering Timothy Leary, PhD, bad trips, and psychosis. “We’ve been down this road before,” the gentleman next to me commented.
Dr. Griffiths went on to talk about trials of psilocybin in clinical populations. In one study, the effects of psilocybin were examined in cancer patients with depression and anxiety. Of the 51 cancer patients, half previously had been treated with psychotropic medications before coming to the study. This randomized, double-blind crossover study compared high-dose psilocybin with an extremely low dose of psilocybin used as the placebo.
Another study looked at patients with major depression who, like the patient interviewed, had not had full resolution of symptoms with conventional antidepressants. Of the 24 participants in that group, 69% reported clinically significant improvement 12 weeks after the treatment. Just over half of participants reported a full remission to normal.
Dr. Griffiths ended by concluding that the positive experiences people have with psilocybin are associated with “enduring positive trait changes in attitudes, mood and behavior, spirituality, and altruism ... and that such experiences are now amenable to systematic prospective scientific study.”
J. Raymond DePaulo, MD, chair of the National Network of Depression Centers and former chair of psychiatry at Johns Hopkins, noted that he used to be skeptical. He has been impressed that Dr. Griffiths has listened to criticism and addressed concerns others have raised. “When it was suggested that this was the result of delirium, he started giving people cognitive tests while they were using psilocybin and he showed it wasn’t the case.”
“I have always objected to words like ‘psychedelic’ and ‘hallucinogen,’ ” said Dr. DePaulo. “They are confusing and inaccurate. No one takes these medications because they want to hallucinate. They take them to change their mood. That said, I am thrilled that we are on the precipice of being able to use this to treat depression.”
Since 1999, the Johns Hopkins Psilocybin Research Project has conducted more than 700 sessions with 369 participants. When might psilocybin be available to patients outside of a research protocol? Two companies have obtained approval from the Food and Drug Administration to initiate registration in trials for treatment of depression. Dr. Griffiths estimates that it could be another 5 years before psilocybin will be available for medical use.
The new center with its generous funding will allow for more studies with more patient populations. The center’s projects will look at using psilocybin as a treatment for opioid use disorder, comorbid depression and alcohol use disorder, anorexia nervosa, depression in Alzheimer’s disease, posttreatment Lyme disease syndrome, and PTSD.
Scott Aaronson, MD, is a mood disorder expert and director of clinical research at the Sheppard Pratt Health System in Towson/Baltimore. Dr. Aaronson, who also studies psilocybin as a treatment for depression, noted: “The problem with the development of psychedelics is that we are not really prepared to capture the improvement we see with their use, as the main changes are not in the classic markers of depression like the Montgomery-Åsberg or the Hamilton Depression rating scales, but [rather] in the patient’s perception of who they are, how they fit in with the world, and what is most important. We need to develop ways to capture those critical changes and work with the FDA to develop an entirely new vision of what constitutes improvement in psychiatric illness. My overall take is that it is a terrific time to specialize in treatment-resistant mood disorders!”
Dr. Miller is coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.
Making and using guidelines
Modern medicine increasingly relies on the adoption and use of guidelines.
Forty years ago, medicine was like free-form, rhythmic gymnastics in which physicians would develop an artisanal treatment plan for each patient. Now, medicine frequently involves recognizing when we need to do a triple-twisting, double-back somersault (the Biles II) and then performing it. The belief is that better outcomes flow from reduced variability in diagnostic and treatment plans, based on guidelines developed from evidence-based medicine from large meta-analyses. This dogma, still unproven in real life, probably works best for 95% of patients. The physician must not omit a step of deciding whether their particular patient is one of the 5% of patients to whom the guideline does not apply.
To be useful, the guidelines must be based on accurate science, produce a significantly positive cost-benefit-risk analysis, be wisely constructed, and be clearly written.
Alas, many guidelines fall far short of this ideal, and when they fail, they impugn all of medical care, they lower the credibility of the organizations that issue them, and they lower the public’s trust in medicine, which thereby impedes improving the public health. Don’t sweat the small stuff for public health guidelines.
The science matters. Nutritional guidelines have been particularly rickety, as John P.A. Ioannidis, MD, wrote in a JAMA op-ed 1 year ago.1 For instance, previous dietary recommendations to reduce cholesterol by avoiding eggs have since been shown to be wrong. The recommendation for reducing salt intake has been heavily criticized. Now the decades-long condemnation of red meat has been challenged. New “guidelines,” suggested by one group (let’s view it as a minority report that contradicts many official guidelines) in the October 1, 2019, issue of Annals of Internal Medicine, say that red meat and processed meats aren’t the boogeyman.2 The authors of the accompanying editorial are from the Center for Pediatric and Adolescent Comparative Effectiveness Research at Indiana University, Indianapolis.3 The editorial supports the new study, criticizing past recommendations because “the field of nutritional epidemiology is plagued by observational studies that have conducted inappropriate analyses, accompanied by likely erroneous conclusions.”
Clarity also matters. One factor in the current opiate epidemic was guidance in the mid-1990s making pain the “fifth vital sign.” This certainly was not the only factor nor was it necessarily the primary one. Most disasters, like most codes on the ward, proceed from multiple smaller failures and missteps. An emphasis on assessing pain in hospitalized patients did not intend to be interpreted as requiring that all pain be eliminated with strong medication, but that was the practical consequence. In response to the epidemic of overdose deaths, guidelines were promulgated in 2016 recommending reducing doses used for chronic opiate regimens. Some patients with chronic pain feared, and soon experienced, the consequences of those changes. In October 2019, those guidelines were revised telling physicians to go slower.4 In explaining the revision, one government official is quoted as saying: “Clearly we believe that there has been misinterpretation of the guidelines, which were very clear.”5 F. Scott Fitzgerald once wrote that “the test of a first-rate intelligence is the ability to hold two opposed ideas in mind at the same time and still retain the ability to function.” I reread that governmental doublespeak three times and my brain broke.
Clinical practice guidelines are an important part of modern medicine. But we need to be wiser about their creation. The science needs to be rigorous. The committees need to contain skeptics rather than just research scientists and clinicians with a vested interest in the field. The purported benefits of the guideline must be weighed against costs, risks, and unintended consequences. Humility is important. All physicians are taught the principle: “First, do no harm.” In explaining medical ethics to students, I rephrase that principle as: “Be cautious and humble. You are not as smart as you think you are.” Consider this food for thought the next time you read or create a guideline.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. JAMA. 2018;320(10):969-70.
2. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.
3. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-2620.
4. U.S. Department of Health & Human Services. HHS guide for clinicians on the appropriate dosage reduction or discontinuation of opioid analgesics. https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf.
5. “New guidelines on opioid tapering tell doctors to go slow.” Washington Post. 2019 Oct 10.
Modern medicine increasingly relies on the adoption and use of guidelines.
Forty years ago, medicine was like free-form, rhythmic gymnastics in which physicians would develop an artisanal treatment plan for each patient. Now, medicine frequently involves recognizing when we need to do a triple-twisting, double-back somersault (the Biles II) and then performing it. The belief is that better outcomes flow from reduced variability in diagnostic and treatment plans, based on guidelines developed from evidence-based medicine from large meta-analyses. This dogma, still unproven in real life, probably works best for 95% of patients. The physician must not omit a step of deciding whether their particular patient is one of the 5% of patients to whom the guideline does not apply.
To be useful, the guidelines must be based on accurate science, produce a significantly positive cost-benefit-risk analysis, be wisely constructed, and be clearly written.
Alas, many guidelines fall far short of this ideal, and when they fail, they impugn all of medical care, they lower the credibility of the organizations that issue them, and they lower the public’s trust in medicine, which thereby impedes improving the public health. Don’t sweat the small stuff for public health guidelines.
The science matters. Nutritional guidelines have been particularly rickety, as John P.A. Ioannidis, MD, wrote in a JAMA op-ed 1 year ago.1 For instance, previous dietary recommendations to reduce cholesterol by avoiding eggs have since been shown to be wrong. The recommendation for reducing salt intake has been heavily criticized. Now the decades-long condemnation of red meat has been challenged. New “guidelines,” suggested by one group (let’s view it as a minority report that contradicts many official guidelines) in the October 1, 2019, issue of Annals of Internal Medicine, say that red meat and processed meats aren’t the boogeyman.2 The authors of the accompanying editorial are from the Center for Pediatric and Adolescent Comparative Effectiveness Research at Indiana University, Indianapolis.3 The editorial supports the new study, criticizing past recommendations because “the field of nutritional epidemiology is plagued by observational studies that have conducted inappropriate analyses, accompanied by likely erroneous conclusions.”
Clarity also matters. One factor in the current opiate epidemic was guidance in the mid-1990s making pain the “fifth vital sign.” This certainly was not the only factor nor was it necessarily the primary one. Most disasters, like most codes on the ward, proceed from multiple smaller failures and missteps. An emphasis on assessing pain in hospitalized patients did not intend to be interpreted as requiring that all pain be eliminated with strong medication, but that was the practical consequence. In response to the epidemic of overdose deaths, guidelines were promulgated in 2016 recommending reducing doses used for chronic opiate regimens. Some patients with chronic pain feared, and soon experienced, the consequences of those changes. In October 2019, those guidelines were revised telling physicians to go slower.4 In explaining the revision, one government official is quoted as saying: “Clearly we believe that there has been misinterpretation of the guidelines, which were very clear.”5 F. Scott Fitzgerald once wrote that “the test of a first-rate intelligence is the ability to hold two opposed ideas in mind at the same time and still retain the ability to function.” I reread that governmental doublespeak three times and my brain broke.
Clinical practice guidelines are an important part of modern medicine. But we need to be wiser about their creation. The science needs to be rigorous. The committees need to contain skeptics rather than just research scientists and clinicians with a vested interest in the field. The purported benefits of the guideline must be weighed against costs, risks, and unintended consequences. Humility is important. All physicians are taught the principle: “First, do no harm.” In explaining medical ethics to students, I rephrase that principle as: “Be cautious and humble. You are not as smart as you think you are.” Consider this food for thought the next time you read or create a guideline.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. JAMA. 2018;320(10):969-70.
2. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.
3. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-2620.
4. U.S. Department of Health & Human Services. HHS guide for clinicians on the appropriate dosage reduction or discontinuation of opioid analgesics. https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf.
5. “New guidelines on opioid tapering tell doctors to go slow.” Washington Post. 2019 Oct 10.
Modern medicine increasingly relies on the adoption and use of guidelines.
Forty years ago, medicine was like free-form, rhythmic gymnastics in which physicians would develop an artisanal treatment plan for each patient. Now, medicine frequently involves recognizing when we need to do a triple-twisting, double-back somersault (the Biles II) and then performing it. The belief is that better outcomes flow from reduced variability in diagnostic and treatment plans, based on guidelines developed from evidence-based medicine from large meta-analyses. This dogma, still unproven in real life, probably works best for 95% of patients. The physician must not omit a step of deciding whether their particular patient is one of the 5% of patients to whom the guideline does not apply.
To be useful, the guidelines must be based on accurate science, produce a significantly positive cost-benefit-risk analysis, be wisely constructed, and be clearly written.
Alas, many guidelines fall far short of this ideal, and when they fail, they impugn all of medical care, they lower the credibility of the organizations that issue them, and they lower the public’s trust in medicine, which thereby impedes improving the public health. Don’t sweat the small stuff for public health guidelines.
The science matters. Nutritional guidelines have been particularly rickety, as John P.A. Ioannidis, MD, wrote in a JAMA op-ed 1 year ago.1 For instance, previous dietary recommendations to reduce cholesterol by avoiding eggs have since been shown to be wrong. The recommendation for reducing salt intake has been heavily criticized. Now the decades-long condemnation of red meat has been challenged. New “guidelines,” suggested by one group (let’s view it as a minority report that contradicts many official guidelines) in the October 1, 2019, issue of Annals of Internal Medicine, say that red meat and processed meats aren’t the boogeyman.2 The authors of the accompanying editorial are from the Center for Pediatric and Adolescent Comparative Effectiveness Research at Indiana University, Indianapolis.3 The editorial supports the new study, criticizing past recommendations because “the field of nutritional epidemiology is plagued by observational studies that have conducted inappropriate analyses, accompanied by likely erroneous conclusions.”
Clarity also matters. One factor in the current opiate epidemic was guidance in the mid-1990s making pain the “fifth vital sign.” This certainly was not the only factor nor was it necessarily the primary one. Most disasters, like most codes on the ward, proceed from multiple smaller failures and missteps. An emphasis on assessing pain in hospitalized patients did not intend to be interpreted as requiring that all pain be eliminated with strong medication, but that was the practical consequence. In response to the epidemic of overdose deaths, guidelines were promulgated in 2016 recommending reducing doses used for chronic opiate regimens. Some patients with chronic pain feared, and soon experienced, the consequences of those changes. In October 2019, those guidelines were revised telling physicians to go slower.4 In explaining the revision, one government official is quoted as saying: “Clearly we believe that there has been misinterpretation of the guidelines, which were very clear.”5 F. Scott Fitzgerald once wrote that “the test of a first-rate intelligence is the ability to hold two opposed ideas in mind at the same time and still retain the ability to function.” I reread that governmental doublespeak three times and my brain broke.
Clinical practice guidelines are an important part of modern medicine. But we need to be wiser about their creation. The science needs to be rigorous. The committees need to contain skeptics rather than just research scientists and clinicians with a vested interest in the field. The purported benefits of the guideline must be weighed against costs, risks, and unintended consequences. Humility is important. All physicians are taught the principle: “First, do no harm.” In explaining medical ethics to students, I rephrase that principle as: “Be cautious and humble. You are not as smart as you think you are.” Consider this food for thought the next time you read or create a guideline.
Dr. Powell is a pediatric hospitalist and clinical ethics consultant living in St. Louis. Email him at [email protected].
References
1. JAMA. 2018;320(10):969-70.
2. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-1621.
3. Ann Intern Med. 2019 Oct 1. doi: 10.7326/M19-2620.
4. U.S. Department of Health & Human Services. HHS guide for clinicians on the appropriate dosage reduction or discontinuation of opioid analgesics. https://www.hhs.gov/opioids/sites/default/files/2019-10/Dosage_Reduction_Discontinuation.pdf.
5. “New guidelines on opioid tapering tell doctors to go slow.” Washington Post. 2019 Oct 10.
Help wanted
In a Pediatrics article, Hsuan-hsiu Annie Chen, MD, offers a very personal and candid narrative of her struggle with depression during medical school and residency (Pediatrics. 2019 Sep 1. doi: 10.1542/peds.2019-1210). Dr. Chen knows from personal experience that she was not alone in her cohort as she faced the challenges of sleep deprivation and emotional trauma that continue to be a part of a physician’s education and training. In her discussion of how future medical trainees might be spared some of the long hours she endured, Dr. Chen suggests that this country consider expanding its physician workforce by “increasing the number of medical schools and recruiting foreign medical graduates” as some European countries have done. Dr. Chen now works in the pediatric residency office at Children’s Hospital, Los Angeles.
Ironically, or maybe it was intentionally, the editors of Pediatrics chose to open the same issue in which Dr. Chen’s personal story appears with a Pediatrics Perspective commentary that looks into the murky waters of physician workforce research (Pediatrics. 2019 Sep 1. doi: 10.1542/peds.2019-0469). Gary L. Freed, MD, MPH, at the Child Health Evaluation and Research Center at the University of Michigan, Ann Arbor, claims that, in general, the data currently being generated by workforce research must be interpreted with caution because many of the studies are flawed by one or more biases.
You may have survived the gauntlet of medical school and residency relatively unscathed. But Is part of the problem that your clinic is seeing too many patients with too few physicians? Do your colleagues share your opinion? Is the administration actively recruiting more physicians, but failing to find interested and qualified doctors? Is this a strictly local phenomenon limited to your community, or is it a regional shortage? Do you think your situation reflects a national trend that deserves attention?
Like Dr. Chen, do you think that more medical schools and active recruitment of foreign medical students would allow you to work less hours? Obviously, even if you were a teenager when you entered your residency, opening more medical schools is not going to allow you to shorten your workday. But are more medical schools the best solution for this country’s overworked physicians even in the long term? Dr. Freed’s observations should make you hesitant to even venture a guess.
You, I, and Dr. Chen only can report on how we perceive our own work environment. Your local physician shortage may be in part because the school system in your community has a poor reputation and young physicians don’t want to move there. It may be that the hospital that owns your practice is struggling and can’t afford to offer a competitive salary. Producing more physicians may not be the answer to the physician shortage in communities like yours, even in the long run.
This is a very large country with relatively porous boundaries between the states for physicians. Physician supply and demand seldom dictates where physicians choose to practice. In fact, a medically needy community is probably the least likely place a physician just finishing her training will choose to settle.
Although adding another physician to your practice may decrease your workload, can your personal finances handle the hit that might occur as you see less patients? Particularly, if the new hire turns out to be a rock star who siphons off more of your patients than you anticipated. On the other hand, there is always the chance that, despite careful vetting, your group hires a lemon who ends up creating more trouble than he is worth.
As Dr. Freed suggests, trying to determine just how many and what kind of physicians we need is complicated. It may be just a roll of the dice at best.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
In a Pediatrics article, Hsuan-hsiu Annie Chen, MD, offers a very personal and candid narrative of her struggle with depression during medical school and residency (Pediatrics. 2019 Sep 1. doi: 10.1542/peds.2019-1210). Dr. Chen knows from personal experience that she was not alone in her cohort as she faced the challenges of sleep deprivation and emotional trauma that continue to be a part of a physician’s education and training. In her discussion of how future medical trainees might be spared some of the long hours she endured, Dr. Chen suggests that this country consider expanding its physician workforce by “increasing the number of medical schools and recruiting foreign medical graduates” as some European countries have done. Dr. Chen now works in the pediatric residency office at Children’s Hospital, Los Angeles.
Ironically, or maybe it was intentionally, the editors of Pediatrics chose to open the same issue in which Dr. Chen’s personal story appears with a Pediatrics Perspective commentary that looks into the murky waters of physician workforce research (Pediatrics. 2019 Sep 1. doi: 10.1542/peds.2019-0469). Gary L. Freed, MD, MPH, at the Child Health Evaluation and Research Center at the University of Michigan, Ann Arbor, claims that, in general, the data currently being generated by workforce research must be interpreted with caution because many of the studies are flawed by one or more biases.
You may have survived the gauntlet of medical school and residency relatively unscathed. But Is part of the problem that your clinic is seeing too many patients with too few physicians? Do your colleagues share your opinion? Is the administration actively recruiting more physicians, but failing to find interested and qualified doctors? Is this a strictly local phenomenon limited to your community, or is it a regional shortage? Do you think your situation reflects a national trend that deserves attention?
Like Dr. Chen, do you think that more medical schools and active recruitment of foreign medical students would allow you to work less hours? Obviously, even if you were a teenager when you entered your residency, opening more medical schools is not going to allow you to shorten your workday. But are more medical schools the best solution for this country’s overworked physicians even in the long term? Dr. Freed’s observations should make you hesitant to even venture a guess.
You, I, and Dr. Chen only can report on how we perceive our own work environment. Your local physician shortage may be in part because the school system in your community has a poor reputation and young physicians don’t want to move there. It may be that the hospital that owns your practice is struggling and can’t afford to offer a competitive salary. Producing more physicians may not be the answer to the physician shortage in communities like yours, even in the long run.
This is a very large country with relatively porous boundaries between the states for physicians. Physician supply and demand seldom dictates where physicians choose to practice. In fact, a medically needy community is probably the least likely place a physician just finishing her training will choose to settle.
Although adding another physician to your practice may decrease your workload, can your personal finances handle the hit that might occur as you see less patients? Particularly, if the new hire turns out to be a rock star who siphons off more of your patients than you anticipated. On the other hand, there is always the chance that, despite careful vetting, your group hires a lemon who ends up creating more trouble than he is worth.
As Dr. Freed suggests, trying to determine just how many and what kind of physicians we need is complicated. It may be just a roll of the dice at best.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
In a Pediatrics article, Hsuan-hsiu Annie Chen, MD, offers a very personal and candid narrative of her struggle with depression during medical school and residency (Pediatrics. 2019 Sep 1. doi: 10.1542/peds.2019-1210). Dr. Chen knows from personal experience that she was not alone in her cohort as she faced the challenges of sleep deprivation and emotional trauma that continue to be a part of a physician’s education and training. In her discussion of how future medical trainees might be spared some of the long hours she endured, Dr. Chen suggests that this country consider expanding its physician workforce by “increasing the number of medical schools and recruiting foreign medical graduates” as some European countries have done. Dr. Chen now works in the pediatric residency office at Children’s Hospital, Los Angeles.
Ironically, or maybe it was intentionally, the editors of Pediatrics chose to open the same issue in which Dr. Chen’s personal story appears with a Pediatrics Perspective commentary that looks into the murky waters of physician workforce research (Pediatrics. 2019 Sep 1. doi: 10.1542/peds.2019-0469). Gary L. Freed, MD, MPH, at the Child Health Evaluation and Research Center at the University of Michigan, Ann Arbor, claims that, in general, the data currently being generated by workforce research must be interpreted with caution because many of the studies are flawed by one or more biases.
You may have survived the gauntlet of medical school and residency relatively unscathed. But Is part of the problem that your clinic is seeing too many patients with too few physicians? Do your colleagues share your opinion? Is the administration actively recruiting more physicians, but failing to find interested and qualified doctors? Is this a strictly local phenomenon limited to your community, or is it a regional shortage? Do you think your situation reflects a national trend that deserves attention?
Like Dr. Chen, do you think that more medical schools and active recruitment of foreign medical students would allow you to work less hours? Obviously, even if you were a teenager when you entered your residency, opening more medical schools is not going to allow you to shorten your workday. But are more medical schools the best solution for this country’s overworked physicians even in the long term? Dr. Freed’s observations should make you hesitant to even venture a guess.
You, I, and Dr. Chen only can report on how we perceive our own work environment. Your local physician shortage may be in part because the school system in your community has a poor reputation and young physicians don’t want to move there. It may be that the hospital that owns your practice is struggling and can’t afford to offer a competitive salary. Producing more physicians may not be the answer to the physician shortage in communities like yours, even in the long run.
This is a very large country with relatively porous boundaries between the states for physicians. Physician supply and demand seldom dictates where physicians choose to practice. In fact, a medically needy community is probably the least likely place a physician just finishing her training will choose to settle.
Although adding another physician to your practice may decrease your workload, can your personal finances handle the hit that might occur as you see less patients? Particularly, if the new hire turns out to be a rock star who siphons off more of your patients than you anticipated. On the other hand, there is always the chance that, despite careful vetting, your group hires a lemon who ends up creating more trouble than he is worth.
As Dr. Freed suggests, trying to determine just how many and what kind of physicians we need is complicated. It may be just a roll of the dice at best.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].