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What To Do With Lipoprotein(a)?
Case: 45-year-old woman comes to clinic and requests lipoprotein(a) [Lp(a)] testing. She has a family history of early coronary disease (mother age 50, sister age 48) and has hypertension with home blood pressure readings of 130-140/70-75. She had a lipid panel checked last year which showed a total cholesterol of 210 mg/dL, LDL 145 mg/dL, HDL 45 mg/dL, and triglycerides of 100 mg/dL. She does not smoke and is currently taking irbesartan, chlorthalidone, sertraline, a multivitamin, and vitamin D.
What do you recommend?
There has been a great deal of media attention on testing for Lp(a). Many of my patients are requesting testing although many of them do not need it. This patient is an exception. I think Lp(a) testing would help inform her medical care. She has a family history of early coronary disease in her mother and sister, but her own lipid profile is not worrisome.
Her 10-year cardiovascular disease risk is 2%. The cardiac risk calculator does not incorporate family history; I think this is a situation where testing for Lp(a)(as well as apolipoprotein B) can be helpful. If her Lp(a) is elevated, it helps reassess her risk and that information would be helpful in targeting aggressive interventions for other CV risk factors, including optimal blood pressure control. In her case, pushing for a goal systolic blood pressure below 120 mm Hg and making sure she is doing regular exercise and eating a heart-healthy diet. The current consensus statement on Lp(a) recommends that patients with elevated levels have aggressive lifestyle and cardiovascular risk management.1
Currently, there are no medical treatments available for high Lp(a) for primary prevention. Apheresis has been approved by the US Food and Drug Administration (FDA) for patients with familial hyperlipidemia who have LDL ≥ 100 mg/dL, Lp(a) ≥ 60 mg/dL, and coronary or other artery disease.
PCSK9 inhibitors have shown a reduction in major cardiovascular events in patients who have established coronary artery disease and high Lp(a) levels, albeit with limited data. Unlike statins, which increase Lp(a) levels, PCSK9 inhibitors reduce Lp(a) levels.2 There are promising early results in a phase 2 trial of the oral drug muvalaplin lowering Lp(a) levels by up to 85% for the highest dose, but there are no peer-reviewed articles confirming these results and no outcome trials at this time.
In patients who are already recognized as high risk, especially those with established coronary artery disease, measuring Lp(a) levels offer little benefit. These patients should already be receiving aggressive medical therapy to reach blood pressure targets if hypertensive, maximal lifestyle modifications, and statin therapy.
If these patients need more therapy because of continued coronary events, despite maximal conventional medical therapy, then adding a PCSK9 inhibitor would be appropriate whether or not a patient has a high Lp(a) level. Once Lp(a) targeted therapies are available and show clinical benefit, then the role of Lp(a) measurement and treatment in this population will be clearer.
Pearl: Most patients do not need Lp(a) testing. There are no FDA-approved treatments for high Lp(a) levels.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Kronenberg F et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43:3925-46.
2. Ruscica M et al. Lipoprotein(a) and PCSK9 inhibition: Clinical evidence Eur Heart J Suppl 2020;Nov 18(Suppl L):L53–L56.
Case: 45-year-old woman comes to clinic and requests lipoprotein(a) [Lp(a)] testing. She has a family history of early coronary disease (mother age 50, sister age 48) and has hypertension with home blood pressure readings of 130-140/70-75. She had a lipid panel checked last year which showed a total cholesterol of 210 mg/dL, LDL 145 mg/dL, HDL 45 mg/dL, and triglycerides of 100 mg/dL. She does not smoke and is currently taking irbesartan, chlorthalidone, sertraline, a multivitamin, and vitamin D.
What do you recommend?
There has been a great deal of media attention on testing for Lp(a). Many of my patients are requesting testing although many of them do not need it. This patient is an exception. I think Lp(a) testing would help inform her medical care. She has a family history of early coronary disease in her mother and sister, but her own lipid profile is not worrisome.
Her 10-year cardiovascular disease risk is 2%. The cardiac risk calculator does not incorporate family history; I think this is a situation where testing for Lp(a)(as well as apolipoprotein B) can be helpful. If her Lp(a) is elevated, it helps reassess her risk and that information would be helpful in targeting aggressive interventions for other CV risk factors, including optimal blood pressure control. In her case, pushing for a goal systolic blood pressure below 120 mm Hg and making sure she is doing regular exercise and eating a heart-healthy diet. The current consensus statement on Lp(a) recommends that patients with elevated levels have aggressive lifestyle and cardiovascular risk management.1
Currently, there are no medical treatments available for high Lp(a) for primary prevention. Apheresis has been approved by the US Food and Drug Administration (FDA) for patients with familial hyperlipidemia who have LDL ≥ 100 mg/dL, Lp(a) ≥ 60 mg/dL, and coronary or other artery disease.
PCSK9 inhibitors have shown a reduction in major cardiovascular events in patients who have established coronary artery disease and high Lp(a) levels, albeit with limited data. Unlike statins, which increase Lp(a) levels, PCSK9 inhibitors reduce Lp(a) levels.2 There are promising early results in a phase 2 trial of the oral drug muvalaplin lowering Lp(a) levels by up to 85% for the highest dose, but there are no peer-reviewed articles confirming these results and no outcome trials at this time.
In patients who are already recognized as high risk, especially those with established coronary artery disease, measuring Lp(a) levels offer little benefit. These patients should already be receiving aggressive medical therapy to reach blood pressure targets if hypertensive, maximal lifestyle modifications, and statin therapy.
If these patients need more therapy because of continued coronary events, despite maximal conventional medical therapy, then adding a PCSK9 inhibitor would be appropriate whether or not a patient has a high Lp(a) level. Once Lp(a) targeted therapies are available and show clinical benefit, then the role of Lp(a) measurement and treatment in this population will be clearer.
Pearl: Most patients do not need Lp(a) testing. There are no FDA-approved treatments for high Lp(a) levels.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Kronenberg F et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43:3925-46.
2. Ruscica M et al. Lipoprotein(a) and PCSK9 inhibition: Clinical evidence Eur Heart J Suppl 2020;Nov 18(Suppl L):L53–L56.
Case: 45-year-old woman comes to clinic and requests lipoprotein(a) [Lp(a)] testing. She has a family history of early coronary disease (mother age 50, sister age 48) and has hypertension with home blood pressure readings of 130-140/70-75. She had a lipid panel checked last year which showed a total cholesterol of 210 mg/dL, LDL 145 mg/dL, HDL 45 mg/dL, and triglycerides of 100 mg/dL. She does not smoke and is currently taking irbesartan, chlorthalidone, sertraline, a multivitamin, and vitamin D.
What do you recommend?
There has been a great deal of media attention on testing for Lp(a). Many of my patients are requesting testing although many of them do not need it. This patient is an exception. I think Lp(a) testing would help inform her medical care. She has a family history of early coronary disease in her mother and sister, but her own lipid profile is not worrisome.
Her 10-year cardiovascular disease risk is 2%. The cardiac risk calculator does not incorporate family history; I think this is a situation where testing for Lp(a)(as well as apolipoprotein B) can be helpful. If her Lp(a) is elevated, it helps reassess her risk and that information would be helpful in targeting aggressive interventions for other CV risk factors, including optimal blood pressure control. In her case, pushing for a goal systolic blood pressure below 120 mm Hg and making sure she is doing regular exercise and eating a heart-healthy diet. The current consensus statement on Lp(a) recommends that patients with elevated levels have aggressive lifestyle and cardiovascular risk management.1
Currently, there are no medical treatments available for high Lp(a) for primary prevention. Apheresis has been approved by the US Food and Drug Administration (FDA) for patients with familial hyperlipidemia who have LDL ≥ 100 mg/dL, Lp(a) ≥ 60 mg/dL, and coronary or other artery disease.
PCSK9 inhibitors have shown a reduction in major cardiovascular events in patients who have established coronary artery disease and high Lp(a) levels, albeit with limited data. Unlike statins, which increase Lp(a) levels, PCSK9 inhibitors reduce Lp(a) levels.2 There are promising early results in a phase 2 trial of the oral drug muvalaplin lowering Lp(a) levels by up to 85% for the highest dose, but there are no peer-reviewed articles confirming these results and no outcome trials at this time.
In patients who are already recognized as high risk, especially those with established coronary artery disease, measuring Lp(a) levels offer little benefit. These patients should already be receiving aggressive medical therapy to reach blood pressure targets if hypertensive, maximal lifestyle modifications, and statin therapy.
If these patients need more therapy because of continued coronary events, despite maximal conventional medical therapy, then adding a PCSK9 inhibitor would be appropriate whether or not a patient has a high Lp(a) level. Once Lp(a) targeted therapies are available and show clinical benefit, then the role of Lp(a) measurement and treatment in this population will be clearer.
Pearl: Most patients do not need Lp(a) testing. There are no FDA-approved treatments for high Lp(a) levels.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at dpaauw@uw.edu.
References
1. Kronenberg F et al. Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: A European Atherosclerosis Society consensus statement. Eur Heart J. 2022;43:3925-46.
2. Ruscica M et al. Lipoprotein(a) and PCSK9 inhibition: Clinical evidence Eur Heart J Suppl 2020;Nov 18(Suppl L):L53–L56.
From Fish Tanks to Cartoons
There was a recent Sermo post bemoaning the demise of fish tanks, and the calming they bring, in medical waiting rooms.
Aquariums, I agree, have a soporific effect on humans. I’m not immune myself on the rare occasions I encounter one. There’s something relaxing about watching the fish slowly glide back and forth while you admire their different colors, sizes, and patterns. This is why they persisted in a lot of places, such as videotapes (remember “Video Fish Tank”?), screen savers, and a key plot point in Finding Nemo.
Personally, When I get the occasional offer for a free waiting room TV that will play some customized feed about my practice and “ask your doctor” treatments, I send it off to be recycled into kitchen towels.
I think the real reason fish tanks are gone is that eternal bugaboo of medicine: money.
Margins in most practices, including mine, are thin, and a real fish tank (I’m not talking about a guppy in a bowl) aren’t cheap. They take, well, fish, and the most colorful ones are saltwater. Then they take a pump, heater, chemicals, food, plants, and decorations. Then you have to throw in the cost of a service with expertise in maintaining them (let’s face it, none of us have time to do that ourselves) ...
You want to add that to your overhead? Me neither.
My waiting room, as a result, is pretty bland. A handful of magazines, some books of classic Far Side, Calvin & Hobbes, and Doonesbury cartoons. The magazines are older, but relatively timeless ones, like issues of the Smithsonian or National Geographic. I don’t put out news magazines of any kind. If I’m not going to read the news, my patients shouldn’t have to either. My lobby should be relaxing.
We also live in an era where patients bring their own entertainment, on phones or iPads, to read while waiting. There are often days when I straighten up the waiting room while closing and the magazines haven’t been touched.
Yes, I miss fish tanks. But, like so many other things, they’ve become a casualty of modern medicine. They simply don’t make financial sense.
I’d rather cut corners in the waiting room than with patient care.
Block has a solo neurology practice in Scottsdale, Arizona.
There was a recent Sermo post bemoaning the demise of fish tanks, and the calming they bring, in medical waiting rooms.
Aquariums, I agree, have a soporific effect on humans. I’m not immune myself on the rare occasions I encounter one. There’s something relaxing about watching the fish slowly glide back and forth while you admire their different colors, sizes, and patterns. This is why they persisted in a lot of places, such as videotapes (remember “Video Fish Tank”?), screen savers, and a key plot point in Finding Nemo.
Personally, When I get the occasional offer for a free waiting room TV that will play some customized feed about my practice and “ask your doctor” treatments, I send it off to be recycled into kitchen towels.
I think the real reason fish tanks are gone is that eternal bugaboo of medicine: money.
Margins in most practices, including mine, are thin, and a real fish tank (I’m not talking about a guppy in a bowl) aren’t cheap. They take, well, fish, and the most colorful ones are saltwater. Then they take a pump, heater, chemicals, food, plants, and decorations. Then you have to throw in the cost of a service with expertise in maintaining them (let’s face it, none of us have time to do that ourselves) ...
You want to add that to your overhead? Me neither.
My waiting room, as a result, is pretty bland. A handful of magazines, some books of classic Far Side, Calvin & Hobbes, and Doonesbury cartoons. The magazines are older, but relatively timeless ones, like issues of the Smithsonian or National Geographic. I don’t put out news magazines of any kind. If I’m not going to read the news, my patients shouldn’t have to either. My lobby should be relaxing.
We also live in an era where patients bring their own entertainment, on phones or iPads, to read while waiting. There are often days when I straighten up the waiting room while closing and the magazines haven’t been touched.
Yes, I miss fish tanks. But, like so many other things, they’ve become a casualty of modern medicine. They simply don’t make financial sense.
I’d rather cut corners in the waiting room than with patient care.
Block has a solo neurology practice in Scottsdale, Arizona.
There was a recent Sermo post bemoaning the demise of fish tanks, and the calming they bring, in medical waiting rooms.
Aquariums, I agree, have a soporific effect on humans. I’m not immune myself on the rare occasions I encounter one. There’s something relaxing about watching the fish slowly glide back and forth while you admire their different colors, sizes, and patterns. This is why they persisted in a lot of places, such as videotapes (remember “Video Fish Tank”?), screen savers, and a key plot point in Finding Nemo.
Personally, When I get the occasional offer for a free waiting room TV that will play some customized feed about my practice and “ask your doctor” treatments, I send it off to be recycled into kitchen towels.
I think the real reason fish tanks are gone is that eternal bugaboo of medicine: money.
Margins in most practices, including mine, are thin, and a real fish tank (I’m not talking about a guppy in a bowl) aren’t cheap. They take, well, fish, and the most colorful ones are saltwater. Then they take a pump, heater, chemicals, food, plants, and decorations. Then you have to throw in the cost of a service with expertise in maintaining them (let’s face it, none of us have time to do that ourselves) ...
You want to add that to your overhead? Me neither.
My waiting room, as a result, is pretty bland. A handful of magazines, some books of classic Far Side, Calvin & Hobbes, and Doonesbury cartoons. The magazines are older, but relatively timeless ones, like issues of the Smithsonian or National Geographic. I don’t put out news magazines of any kind. If I’m not going to read the news, my patients shouldn’t have to either. My lobby should be relaxing.
We also live in an era where patients bring their own entertainment, on phones or iPads, to read while waiting. There are often days when I straighten up the waiting room while closing and the magazines haven’t been touched.
Yes, I miss fish tanks. But, like so many other things, they’ve become a casualty of modern medicine. They simply don’t make financial sense.
I’d rather cut corners in the waiting room than with patient care.
Block has a solo neurology practice in Scottsdale, Arizona.
Exposomania
If we’ve learned anything about obesity prevention it’s that if we wait too long the die is cast and our success rate is nil. The GLP-1 antagonists seem to be a workable solution for treating the adult and adolescent population, but I have been afraid that their success will divert too much of our attention away from prevention.
Fortunately, there still seems to be a few researchers committed to the age group in which obesity could be headed off before our only option is treatment. In one recent study, “Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity,” researchers collected data from more than 28,000 children in 55 cohorts during the period from 1994 to 2023). The investigators found that residence in a low–food access, low-income neighborhoods during pregnancy and early childhood was associated with higher BMI “Z” scores, a higher risk of obesity, and severe obesity in childhood. The researchers defined low food access as living greater than 0.5 miles away from a grocery store in an urban setting or greater than 10 minutes away in a rural setting. I don’t think those associations should surprise us, but having some data from a large population may be valuable should we ever find the political will to undertake any steps toward prevention.
I found a Viewpoint article published 2 weeks earlier in the same journal, titled, “The Exposome as a Key to Understanding Pediatric Health Disparities.” I know what the “biome” is and have heard gastroenterologists expound on the power that billions of our little single-celled friends residing in our gut have on seemingly unrelated and spatially distant events in our body. But, “exposome” was a new word for me, although it turns out the concept is simple and one I had harbored since late childhood.
The opening sentence of the article reads “One’s environment profoundly changes health outcomes throughout one’s lifespan.” That truism was obvious to my 7-year-old self as I observed my playmates who lived in a poorly kept house in the less desirable area two blocks away and didn’t eat breakfast and were sick more often than the rest of us more-fortunates.
The authors define the exposome as the “totality of an individual’s non-genetic exposures, including psychosocial experiences, structural social determinants, chemical pollution, and neighborhood infrastructure.” This seems to be a pretty complete description of the nurture side of the nature versus nurture conversation.
I suspect that, like me, most of you through observation and intuition have included your own interpretation of the exposome in your professional activities. However, the authors feel we could be more robust in our efforts and claim that They go on to call for incorporation of an “exposome lens in pediatric research and healthcare delivery.”
I’m not sure this is a valid criticism. There is certainly more that could be done when it comes to research that examines the effect of environmental stressors. And, I suspect the authors would view this recent paper on the association between neighborhood food access as a step in the right direction. However, when it comes to healthcare delivery, at least at the level where the stethoscope meets the chest, I think, or at least hope, the authors are underestimating the observational skills and sensitivity of primary care providers.
We were all taught to take an appropriate medical history when evaluating a patient. And, through our formal education, our personal observations and through exposure to papers like this one on food access we must be aware of the effect of environmental stressors on our patients’ health. Is there more we could learn about those kind of associations? Certainly. This is where a more broadly focused exposome lens could be most effective.
The authors of the article observed: “The effect of the exposome is not uniform for all individuals but rather intersects across identities precipitating unique outcomes.” The practical reality is that to generate statistically significant data research must look at identities. This doesn’t mean that large population studies are without value. However, it does obligate investigators to include that caveat about the uniqueness of the individual in their conclusions. And, it is our duty as providers to keep this reality in mind as we interpret studies we read in the context of each individual patient.
When it comes to healthcare delivery at the structural level, I am concerned that we are moving in a direction that is making it more difficult for the provider to become familiar with the patient’s exposome. I am talking about an over-reliance on the team care delivery model that too often results in the “We never/seldom see the same provider” patient complaint.
I don’t care how slick and user-friendly a practice’s EHR system is; the best way to learn about a patient’s exposome is by repeated exposure (pun unintended) to the same provider. This isn’t always possible, and a well-crafted and conscientiously managed EHR can fill in some of the gaps. But, it is a distant second best.
Awareness of the importance of the exposome is only the starting point. Finding the political will to make the changes necessary to improve our patients’ outcomes is the bigger challenge. Grocery stores well-stocked with healthy foods don’t just pop up where we want them because we think they may hold answer to preventing pediatric obesity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
If we’ve learned anything about obesity prevention it’s that if we wait too long the die is cast and our success rate is nil. The GLP-1 antagonists seem to be a workable solution for treating the adult and adolescent population, but I have been afraid that their success will divert too much of our attention away from prevention.
Fortunately, there still seems to be a few researchers committed to the age group in which obesity could be headed off before our only option is treatment. In one recent study, “Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity,” researchers collected data from more than 28,000 children in 55 cohorts during the period from 1994 to 2023). The investigators found that residence in a low–food access, low-income neighborhoods during pregnancy and early childhood was associated with higher BMI “Z” scores, a higher risk of obesity, and severe obesity in childhood. The researchers defined low food access as living greater than 0.5 miles away from a grocery store in an urban setting or greater than 10 minutes away in a rural setting. I don’t think those associations should surprise us, but having some data from a large population may be valuable should we ever find the political will to undertake any steps toward prevention.
I found a Viewpoint article published 2 weeks earlier in the same journal, titled, “The Exposome as a Key to Understanding Pediatric Health Disparities.” I know what the “biome” is and have heard gastroenterologists expound on the power that billions of our little single-celled friends residing in our gut have on seemingly unrelated and spatially distant events in our body. But, “exposome” was a new word for me, although it turns out the concept is simple and one I had harbored since late childhood.
The opening sentence of the article reads “One’s environment profoundly changes health outcomes throughout one’s lifespan.” That truism was obvious to my 7-year-old self as I observed my playmates who lived in a poorly kept house in the less desirable area two blocks away and didn’t eat breakfast and were sick more often than the rest of us more-fortunates.
The authors define the exposome as the “totality of an individual’s non-genetic exposures, including psychosocial experiences, structural social determinants, chemical pollution, and neighborhood infrastructure.” This seems to be a pretty complete description of the nurture side of the nature versus nurture conversation.
I suspect that, like me, most of you through observation and intuition have included your own interpretation of the exposome in your professional activities. However, the authors feel we could be more robust in our efforts and claim that They go on to call for incorporation of an “exposome lens in pediatric research and healthcare delivery.”
I’m not sure this is a valid criticism. There is certainly more that could be done when it comes to research that examines the effect of environmental stressors. And, I suspect the authors would view this recent paper on the association between neighborhood food access as a step in the right direction. However, when it comes to healthcare delivery, at least at the level where the stethoscope meets the chest, I think, or at least hope, the authors are underestimating the observational skills and sensitivity of primary care providers.
We were all taught to take an appropriate medical history when evaluating a patient. And, through our formal education, our personal observations and through exposure to papers like this one on food access we must be aware of the effect of environmental stressors on our patients’ health. Is there more we could learn about those kind of associations? Certainly. This is where a more broadly focused exposome lens could be most effective.
The authors of the article observed: “The effect of the exposome is not uniform for all individuals but rather intersects across identities precipitating unique outcomes.” The practical reality is that to generate statistically significant data research must look at identities. This doesn’t mean that large population studies are without value. However, it does obligate investigators to include that caveat about the uniqueness of the individual in their conclusions. And, it is our duty as providers to keep this reality in mind as we interpret studies we read in the context of each individual patient.
When it comes to healthcare delivery at the structural level, I am concerned that we are moving in a direction that is making it more difficult for the provider to become familiar with the patient’s exposome. I am talking about an over-reliance on the team care delivery model that too often results in the “We never/seldom see the same provider” patient complaint.
I don’t care how slick and user-friendly a practice’s EHR system is; the best way to learn about a patient’s exposome is by repeated exposure (pun unintended) to the same provider. This isn’t always possible, and a well-crafted and conscientiously managed EHR can fill in some of the gaps. But, it is a distant second best.
Awareness of the importance of the exposome is only the starting point. Finding the political will to make the changes necessary to improve our patients’ outcomes is the bigger challenge. Grocery stores well-stocked with healthy foods don’t just pop up where we want them because we think they may hold answer to preventing pediatric obesity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
If we’ve learned anything about obesity prevention it’s that if we wait too long the die is cast and our success rate is nil. The GLP-1 antagonists seem to be a workable solution for treating the adult and adolescent population, but I have been afraid that their success will divert too much of our attention away from prevention.
Fortunately, there still seems to be a few researchers committed to the age group in which obesity could be headed off before our only option is treatment. In one recent study, “Neighborhood Food Access in Early Life and Trajectories of Child Body Mass Index and Obesity,” researchers collected data from more than 28,000 children in 55 cohorts during the period from 1994 to 2023). The investigators found that residence in a low–food access, low-income neighborhoods during pregnancy and early childhood was associated with higher BMI “Z” scores, a higher risk of obesity, and severe obesity in childhood. The researchers defined low food access as living greater than 0.5 miles away from a grocery store in an urban setting or greater than 10 minutes away in a rural setting. I don’t think those associations should surprise us, but having some data from a large population may be valuable should we ever find the political will to undertake any steps toward prevention.
I found a Viewpoint article published 2 weeks earlier in the same journal, titled, “The Exposome as a Key to Understanding Pediatric Health Disparities.” I know what the “biome” is and have heard gastroenterologists expound on the power that billions of our little single-celled friends residing in our gut have on seemingly unrelated and spatially distant events in our body. But, “exposome” was a new word for me, although it turns out the concept is simple and one I had harbored since late childhood.
The opening sentence of the article reads “One’s environment profoundly changes health outcomes throughout one’s lifespan.” That truism was obvious to my 7-year-old self as I observed my playmates who lived in a poorly kept house in the less desirable area two blocks away and didn’t eat breakfast and were sick more often than the rest of us more-fortunates.
The authors define the exposome as the “totality of an individual’s non-genetic exposures, including psychosocial experiences, structural social determinants, chemical pollution, and neighborhood infrastructure.” This seems to be a pretty complete description of the nurture side of the nature versus nurture conversation.
I suspect that, like me, most of you through observation and intuition have included your own interpretation of the exposome in your professional activities. However, the authors feel we could be more robust in our efforts and claim that They go on to call for incorporation of an “exposome lens in pediatric research and healthcare delivery.”
I’m not sure this is a valid criticism. There is certainly more that could be done when it comes to research that examines the effect of environmental stressors. And, I suspect the authors would view this recent paper on the association between neighborhood food access as a step in the right direction. However, when it comes to healthcare delivery, at least at the level where the stethoscope meets the chest, I think, or at least hope, the authors are underestimating the observational skills and sensitivity of primary care providers.
We were all taught to take an appropriate medical history when evaluating a patient. And, through our formal education, our personal observations and through exposure to papers like this one on food access we must be aware of the effect of environmental stressors on our patients’ health. Is there more we could learn about those kind of associations? Certainly. This is where a more broadly focused exposome lens could be most effective.
The authors of the article observed: “The effect of the exposome is not uniform for all individuals but rather intersects across identities precipitating unique outcomes.” The practical reality is that to generate statistically significant data research must look at identities. This doesn’t mean that large population studies are without value. However, it does obligate investigators to include that caveat about the uniqueness of the individual in their conclusions. And, it is our duty as providers to keep this reality in mind as we interpret studies we read in the context of each individual patient.
When it comes to healthcare delivery at the structural level, I am concerned that we are moving in a direction that is making it more difficult for the provider to become familiar with the patient’s exposome. I am talking about an over-reliance on the team care delivery model that too often results in the “We never/seldom see the same provider” patient complaint.
I don’t care how slick and user-friendly a practice’s EHR system is; the best way to learn about a patient’s exposome is by repeated exposure (pun unintended) to the same provider. This isn’t always possible, and a well-crafted and conscientiously managed EHR can fill in some of the gaps. But, it is a distant second best.
Awareness of the importance of the exposome is only the starting point. Finding the political will to make the changes necessary to improve our patients’ outcomes is the bigger challenge. Grocery stores well-stocked with healthy foods don’t just pop up where we want them because we think they may hold answer to preventing pediatric obesity.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Recognizing Burnout: Why Physicians Often Miss the Signs in Themselves
Summary and Key Highlights
Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.
Key Takeaways:
- Many physicians struggle to identify burnout due to stigma and self-blame.
- Awareness of burnout symptoms is essential for early intervention and healthy coping.
- Seeking support can prevent burnout from worsening and improve quality of life.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
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Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.
A version of this article first appeared on Medscape.com.
Summary and Key Highlights
Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.
Key Takeaways:
- Many physicians struggle to identify burnout due to stigma and self-blame.
- Awareness of burnout symptoms is essential for early intervention and healthy coping.
- Seeking support can prevent burnout from worsening and improve quality of life.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.
A version of this article first appeared on Medscape.com.
Summary and Key Highlights
Summary: This section explores why physicians often struggle to recognize burnout within themselves, partly due to stigma and a tendency to focus on productivity over well-being. Dr. Tyra Fainstad shares personal experiences of burnout symptoms, emphasizing the importance of awareness and self-reflection. Recognizing and addressing burnout early can help physicians find healthier coping strategies, avoid productivity traps, and seek support.
Key Takeaways:
- Many physicians struggle to identify burnout due to stigma and self-blame.
- Awareness of burnout symptoms is essential for early intervention and healthy coping.
- Seeking support can prevent burnout from worsening and improve quality of life.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.
A version of this article first appeared on Medscape.com.
Breaking the Cycle: Why Self-Compassion Is Essential for Today’s Physicians
Summary and Key Highlights
Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.
Key Takeaways:
- Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
- Practicing self-compassion can improve long-term resilience and prevent burnout.
- The changing landscape of healthcare supports a more balanced approach to physician well-being.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.
A version of this article first appeared on Medscape.com.
Summary and Key Highlights
Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.
Key Takeaways:
- Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
- Practicing self-compassion can improve long-term resilience and prevent burnout.
- The changing landscape of healthcare supports a more balanced approach to physician well-being.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.
A version of this article first appeared on Medscape.com.
Summary and Key Highlights
Summary: Dr Tyra Fainstad explores the ingrained culture in medicine that encourages self-criticism, with many physicians feeling that they must be hard on themselves to succeed. Dr Fainstad challenges this belief, advocating for self-compassion as a healthier alternative. The evolving medical field now includes physicians who prioritize well-being without sacrificing quality of care, underscoring the importance of self-kindness for sustainable practice.
Key Takeaways:
- Many physicians believe that self-criticism is necessary for success, a mindset rooted in medical culture.
- Practicing self-compassion can improve long-term resilience and prevent burnout.
- The changing landscape of healthcare supports a more balanced approach to physician well-being.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
Lotte Dyrbye, has disclosed the following relevant financial relationships: Co-inventor of the Well-being Index and its derivatives, which Mayo Clinic has licensed. Dyrbye receives royalties.
A version of this article first appeared on Medscape.com.
Finding Fulfillment Beyond Metrics: A Physician’s Path to Lasting Well-Being
Summary and Key Highlights
Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.
Key Takeaways:
- Relying solely on external validation can deepen burnout and affect well-being.
- Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
- Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
A version of this article first appeared on Medscape.com.
Summary and Key Highlights
Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.
Key Takeaways:
- Relying solely on external validation can deepen burnout and affect well-being.
- Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
- Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
A version of this article first appeared on Medscape.com.
Summary and Key Highlights
Summary: Dr Tyra Fainstad shares her personal experience with burnout and the journey to recovery through coaching and self-compassion. She describes the pressures of seeking validation through external achievements, which ultimately led to a crisis in self-worth after medical training. Through coaching, she learned to cultivate a sense of internal fulfillment, reconnecting with her passion for medicine and achieving a healthier balance.
Key Takeaways:
- Relying solely on external validation can deepen burnout and affect well-being.
- Coaching empowers physicians to develop self-compassion and sustainable coping strategies.
- Shifting from external to internal validation strengthens long-term fulfillment and job satisfaction.
Our Editors Also Recommend:
Medscape Physician Burnout & Depression Report 2024: ‘We Have Much Work to Do’
Medscape Hospitalist Burnout & Depression Report 2024: Seeking Progress, Balance
Medscape Physician Lifestyle & Happiness Report 2024: The Ongoing Struggle for Balance
A Transformative Rx for Burnout, Grief, and Illness: Dance
Next Medscape Masters Event:
Stay at the forefront of obesity care. Register for exclusive insights and the latest treatment innovations.
A version of this article first appeared on Medscape.com.
Gentle Parenting
In one my recent Letters, I concluded with the concern that infant-led weaning, which makes some sense, can be confused with child-led family meals, which make none. I referred to an increasingly popular style of parenting overemphasizing child autonomy that seems to be a major contributor to the mealtime chaos that occurs when pleasing every palate at the table becomes the goal.
In the intervening weeks, I have learned that this parenting style is called “gentle parenting.” Despite its growing popularity, possibly fueled by the pandemic, it has not been well-defined nor its effectiveness investigated. In a recent paper published in PLOS ONE, two professors of developmental psychology have attempted correct this deficit in our understanding of this parenting style, which doesn’t appear to make sense to many of us with experience in child behavior and development.
Gentle Parents
By surveying a group of 100 parents of young children, the investigators were able to sort out a group of parents (n = 49) who self-identified as employing gentle parenting. Their responses emphasized a high level of parental affection and emotional regulation by both their children and themselves.
Investigators found that 40% of the self-defined gentle parents “had negative difference scores indicating misbehavior response descriptions that included more child directed responses. I interpret this to mean that almost half of the time the parents failed to evenly include themselves in a solution to a conflict, which indicates incomplete or unsuccessful emotional regulation on their part. The investigators also observed that, like many other parenting styles, gentle parenting includes an emphasis on boundaries “yet, enactment of those boundaries is not uniform.”
More telling was the authors’ observation that “statements of parenting uncertainty and burnout were present in over one third of the gentle of the gentle parenting sample.” While some parents were pleased with their experience, the downside seems unacceptable to me. When asked to explain this finding, Annie Pezalla, PhD, one of the coauthors, has said “gentle parenting practices work best when a parent is emotionally regulated and unconstrained for time — commodities that parents struggle with the most.”
Abundance Advice on Parenting Styles
I find this to be a very sad story. Parenting can be difficult. Creating and then gently and effectively policing those boundaries is often the hardest part. It is not surprising to me that of the four books I have written for parents, the one titled How to Say No to Your Toddler is the only one popular enough to be published in four languages.
Of course I am troubled, as I suspect you may be, with the label “gentle parenting.” It implies that the rest of us are doing something terrible, “harsh” maybe, “cruel” maybe. We can dispense with the “affectionate” descriptor immediately because gentle parenting can’t claim sole ownership to it. Every, behavior management scheme I am aware of touts being caring and loving at its core.
I completely agree that emotional regulation for both parent and child are worthy goals, but I’m not hearing much on how that is to be achieved other than by trying to avoid the inevitable conflict by failing to even say “No” when poorly crafted boundaries are breached.
There are scores of parenting styles out there. And there should be, because we are all different. Parents have strengths and weaknesses and they have begotten children with different personalities and vulnerabilities. And, families come from different cultures and socioeconomic backgrounds.
Across all of these differences there are two primary roles for every parent. The first is to lead by example. If a parent wants his/her child to be kind and caring and polite, then the parent has no choice but to behave that way. If the parent can’t always be present, the environment where the child spends most of his/her day should model the desired behavior. I’m not talking about teaching because you can’t preach good behavior. It must be modeled.
The second role for the parent is to keep his/her child safe from dangers that exist in every environment. This can mean accepting vaccines and seeking available medical care. But, it also means creating some limits — the current buzzword is “guardrails” — to keep the child from veering into the ditch.
Setting Limits
Limits will, of necessity, vary with the environment. The risks of a child growing on a farm differ from those of child living in the city. And they must be tailored to the personality and developmental stage of the child. A parent may need advice from someone experienced in child behavior to create individualized limits. You may be able to allow your 3-year-old to roam freely in an environment in which I would have to monitor my risk-taking 3-year-old every second. A parent must learn and accept his/her child’s personality and the environment they can provide.
Limits should be inanimate objects whenever possible. Fences, gates, doors with latches, and locked cabinets to keep temptations out of view, etc. Creative environmental manipulations should be employed to keep the annoying verbal warnings, unenforceable threats, and direct child-to-parent confrontations to a minimum.
Consequences
Challenges to even the most carefully crafted limits are inevitable, and this is where we get to the third-rail topic of consequences. Yes, when prevention has failed for whatever reason, I believe that an intelligently and affectionately applied time-out is the most efficient and most effective consequence. This is not the place for me to explore or defend the details, but before you write me off as an octogenarian hard-ass (or hard-liner if you prefer) I urge you to read a few chapters in How to Say No to Your Toddler.
Far more important than which consequence a parent chooses are the steps the family has taken to keep both parent and child in a state of balanced emotional regulation. Is everyone well rested and getting enough sleep? Sleep deprivation is one of the most potent triggers of a tantrum; it also leaves parents vulnerable to saying things and making threats they will regret later. Does the child’s schedule leave him or her enough time to decompress? Does the parent’s schedule sync with a developmentally appropriate schedule for the child? Is he/she getting the right kind of attention when it makes the most sense to him/her?
Intelligent Parenting
If a family has created an environment in which limits are appropriate for the child’s personality and developmental stage, used physical barriers whenever possible, and kept everyone as well rested as possible, both challenges to the limits and consequences can be kept to a minimum.
But achieving this state requires time as free of constraints as possible. For the few families that have the luxury of meeting these conditions, gentle parenting might be the answer. For the rest of us, intelligent parenting that acknowledges the realities and limits of our own abilities and our children’s vulnerabilities is the better answer.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
In one my recent Letters, I concluded with the concern that infant-led weaning, which makes some sense, can be confused with child-led family meals, which make none. I referred to an increasingly popular style of parenting overemphasizing child autonomy that seems to be a major contributor to the mealtime chaos that occurs when pleasing every palate at the table becomes the goal.
In the intervening weeks, I have learned that this parenting style is called “gentle parenting.” Despite its growing popularity, possibly fueled by the pandemic, it has not been well-defined nor its effectiveness investigated. In a recent paper published in PLOS ONE, two professors of developmental psychology have attempted correct this deficit in our understanding of this parenting style, which doesn’t appear to make sense to many of us with experience in child behavior and development.
Gentle Parents
By surveying a group of 100 parents of young children, the investigators were able to sort out a group of parents (n = 49) who self-identified as employing gentle parenting. Their responses emphasized a high level of parental affection and emotional regulation by both their children and themselves.
Investigators found that 40% of the self-defined gentle parents “had negative difference scores indicating misbehavior response descriptions that included more child directed responses. I interpret this to mean that almost half of the time the parents failed to evenly include themselves in a solution to a conflict, which indicates incomplete or unsuccessful emotional regulation on their part. The investigators also observed that, like many other parenting styles, gentle parenting includes an emphasis on boundaries “yet, enactment of those boundaries is not uniform.”
More telling was the authors’ observation that “statements of parenting uncertainty and burnout were present in over one third of the gentle of the gentle parenting sample.” While some parents were pleased with their experience, the downside seems unacceptable to me. When asked to explain this finding, Annie Pezalla, PhD, one of the coauthors, has said “gentle parenting practices work best when a parent is emotionally regulated and unconstrained for time — commodities that parents struggle with the most.”
Abundance Advice on Parenting Styles
I find this to be a very sad story. Parenting can be difficult. Creating and then gently and effectively policing those boundaries is often the hardest part. It is not surprising to me that of the four books I have written for parents, the one titled How to Say No to Your Toddler is the only one popular enough to be published in four languages.
Of course I am troubled, as I suspect you may be, with the label “gentle parenting.” It implies that the rest of us are doing something terrible, “harsh” maybe, “cruel” maybe. We can dispense with the “affectionate” descriptor immediately because gentle parenting can’t claim sole ownership to it. Every, behavior management scheme I am aware of touts being caring and loving at its core.
I completely agree that emotional regulation for both parent and child are worthy goals, but I’m not hearing much on how that is to be achieved other than by trying to avoid the inevitable conflict by failing to even say “No” when poorly crafted boundaries are breached.
There are scores of parenting styles out there. And there should be, because we are all different. Parents have strengths and weaknesses and they have begotten children with different personalities and vulnerabilities. And, families come from different cultures and socioeconomic backgrounds.
Across all of these differences there are two primary roles for every parent. The first is to lead by example. If a parent wants his/her child to be kind and caring and polite, then the parent has no choice but to behave that way. If the parent can’t always be present, the environment where the child spends most of his/her day should model the desired behavior. I’m not talking about teaching because you can’t preach good behavior. It must be modeled.
The second role for the parent is to keep his/her child safe from dangers that exist in every environment. This can mean accepting vaccines and seeking available medical care. But, it also means creating some limits — the current buzzword is “guardrails” — to keep the child from veering into the ditch.
Setting Limits
Limits will, of necessity, vary with the environment. The risks of a child growing on a farm differ from those of child living in the city. And they must be tailored to the personality and developmental stage of the child. A parent may need advice from someone experienced in child behavior to create individualized limits. You may be able to allow your 3-year-old to roam freely in an environment in which I would have to monitor my risk-taking 3-year-old every second. A parent must learn and accept his/her child’s personality and the environment they can provide.
Limits should be inanimate objects whenever possible. Fences, gates, doors with latches, and locked cabinets to keep temptations out of view, etc. Creative environmental manipulations should be employed to keep the annoying verbal warnings, unenforceable threats, and direct child-to-parent confrontations to a minimum.
Consequences
Challenges to even the most carefully crafted limits are inevitable, and this is where we get to the third-rail topic of consequences. Yes, when prevention has failed for whatever reason, I believe that an intelligently and affectionately applied time-out is the most efficient and most effective consequence. This is not the place for me to explore or defend the details, but before you write me off as an octogenarian hard-ass (or hard-liner if you prefer) I urge you to read a few chapters in How to Say No to Your Toddler.
Far more important than which consequence a parent chooses are the steps the family has taken to keep both parent and child in a state of balanced emotional regulation. Is everyone well rested and getting enough sleep? Sleep deprivation is one of the most potent triggers of a tantrum; it also leaves parents vulnerable to saying things and making threats they will regret later. Does the child’s schedule leave him or her enough time to decompress? Does the parent’s schedule sync with a developmentally appropriate schedule for the child? Is he/she getting the right kind of attention when it makes the most sense to him/her?
Intelligent Parenting
If a family has created an environment in which limits are appropriate for the child’s personality and developmental stage, used physical barriers whenever possible, and kept everyone as well rested as possible, both challenges to the limits and consequences can be kept to a minimum.
But achieving this state requires time as free of constraints as possible. For the few families that have the luxury of meeting these conditions, gentle parenting might be the answer. For the rest of us, intelligent parenting that acknowledges the realities and limits of our own abilities and our children’s vulnerabilities is the better answer.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
In one my recent Letters, I concluded with the concern that infant-led weaning, which makes some sense, can be confused with child-led family meals, which make none. I referred to an increasingly popular style of parenting overemphasizing child autonomy that seems to be a major contributor to the mealtime chaos that occurs when pleasing every palate at the table becomes the goal.
In the intervening weeks, I have learned that this parenting style is called “gentle parenting.” Despite its growing popularity, possibly fueled by the pandemic, it has not been well-defined nor its effectiveness investigated. In a recent paper published in PLOS ONE, two professors of developmental psychology have attempted correct this deficit in our understanding of this parenting style, which doesn’t appear to make sense to many of us with experience in child behavior and development.
Gentle Parents
By surveying a group of 100 parents of young children, the investigators were able to sort out a group of parents (n = 49) who self-identified as employing gentle parenting. Their responses emphasized a high level of parental affection and emotional regulation by both their children and themselves.
Investigators found that 40% of the self-defined gentle parents “had negative difference scores indicating misbehavior response descriptions that included more child directed responses. I interpret this to mean that almost half of the time the parents failed to evenly include themselves in a solution to a conflict, which indicates incomplete or unsuccessful emotional regulation on their part. The investigators also observed that, like many other parenting styles, gentle parenting includes an emphasis on boundaries “yet, enactment of those boundaries is not uniform.”
More telling was the authors’ observation that “statements of parenting uncertainty and burnout were present in over one third of the gentle of the gentle parenting sample.” While some parents were pleased with their experience, the downside seems unacceptable to me. When asked to explain this finding, Annie Pezalla, PhD, one of the coauthors, has said “gentle parenting practices work best when a parent is emotionally regulated and unconstrained for time — commodities that parents struggle with the most.”
Abundance Advice on Parenting Styles
I find this to be a very sad story. Parenting can be difficult. Creating and then gently and effectively policing those boundaries is often the hardest part. It is not surprising to me that of the four books I have written for parents, the one titled How to Say No to Your Toddler is the only one popular enough to be published in four languages.
Of course I am troubled, as I suspect you may be, with the label “gentle parenting.” It implies that the rest of us are doing something terrible, “harsh” maybe, “cruel” maybe. We can dispense with the “affectionate” descriptor immediately because gentle parenting can’t claim sole ownership to it. Every, behavior management scheme I am aware of touts being caring and loving at its core.
I completely agree that emotional regulation for both parent and child are worthy goals, but I’m not hearing much on how that is to be achieved other than by trying to avoid the inevitable conflict by failing to even say “No” when poorly crafted boundaries are breached.
There are scores of parenting styles out there. And there should be, because we are all different. Parents have strengths and weaknesses and they have begotten children with different personalities and vulnerabilities. And, families come from different cultures and socioeconomic backgrounds.
Across all of these differences there are two primary roles for every parent. The first is to lead by example. If a parent wants his/her child to be kind and caring and polite, then the parent has no choice but to behave that way. If the parent can’t always be present, the environment where the child spends most of his/her day should model the desired behavior. I’m not talking about teaching because you can’t preach good behavior. It must be modeled.
The second role for the parent is to keep his/her child safe from dangers that exist in every environment. This can mean accepting vaccines and seeking available medical care. But, it also means creating some limits — the current buzzword is “guardrails” — to keep the child from veering into the ditch.
Setting Limits
Limits will, of necessity, vary with the environment. The risks of a child growing on a farm differ from those of child living in the city. And they must be tailored to the personality and developmental stage of the child. A parent may need advice from someone experienced in child behavior to create individualized limits. You may be able to allow your 3-year-old to roam freely in an environment in which I would have to monitor my risk-taking 3-year-old every second. A parent must learn and accept his/her child’s personality and the environment they can provide.
Limits should be inanimate objects whenever possible. Fences, gates, doors with latches, and locked cabinets to keep temptations out of view, etc. Creative environmental manipulations should be employed to keep the annoying verbal warnings, unenforceable threats, and direct child-to-parent confrontations to a minimum.
Consequences
Challenges to even the most carefully crafted limits are inevitable, and this is where we get to the third-rail topic of consequences. Yes, when prevention has failed for whatever reason, I believe that an intelligently and affectionately applied time-out is the most efficient and most effective consequence. This is not the place for me to explore or defend the details, but before you write me off as an octogenarian hard-ass (or hard-liner if you prefer) I urge you to read a few chapters in How to Say No to Your Toddler.
Far more important than which consequence a parent chooses are the steps the family has taken to keep both parent and child in a state of balanced emotional regulation. Is everyone well rested and getting enough sleep? Sleep deprivation is one of the most potent triggers of a tantrum; it also leaves parents vulnerable to saying things and making threats they will regret later. Does the child’s schedule leave him or her enough time to decompress? Does the parent’s schedule sync with a developmentally appropriate schedule for the child? Is he/she getting the right kind of attention when it makes the most sense to him/her?
Intelligent Parenting
If a family has created an environment in which limits are appropriate for the child’s personality and developmental stage, used physical barriers whenever possible, and kept everyone as well rested as possible, both challenges to the limits and consequences can be kept to a minimum.
But achieving this state requires time as free of constraints as possible. For the few families that have the luxury of meeting these conditions, gentle parenting might be the answer. For the rest of us, intelligent parenting that acknowledges the realities and limits of our own abilities and our children’s vulnerabilities is the better answer.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
Screen Use and Toddler Bedtimes
For decades I have suspected that there is a strong association between sleep deprivation and pediatric attention disorders. More recently I have wondered whether screen time, particularly at bedtime might be a significant contributor to sleep quantity and quality in both children and adults. There is a growing body of research that combines my two observations and suggests that bedtime screen time through its effect on sleep may be linked to pediatric attention problems. However, most of this work is preliminary and needs to be confirmed.
Stumbling across a paper from England titled “Toddler Screen Use Before Bed and Its Effect on Sleep and Attention” renewed my hope that we finally have evidence to close that knowledge gap. My bubble burst quickly however when I jumped ahead and read the conclusion portion of the abstract and learned that authors observed “no clear difference in parent reported attention” in the group of children in which screen time before bedtime had been eliminated. The authors wonder if their small study sample may be to blame.
Disappointed, I persisted and read the paper in its entirety and found that despite their failure to link bedtime screen time with attention disorders, the investigators have made a significant contribution to our understanding of how we can better encourage good pediatric sleep hygiene.
The Study
One hundred and five families with a toddler who was being exposed to a video screen in the hour before bedtime were divided into three groups. One group received guidance and advice from a pediatric team about the potential benefit of eliminating bedtime screen time. They were also given a box of activities that contained “activity cards and age appropriate toys” to replace the screen use. The family also received periodic support and follow-up contacts. A second group received only the “bedtime box.” And the third received no intervention.
It is important to note that the investigators modeled their intervention on one developed in a previous study using older children that was “co-created with caregivers and early years practitioners”(my italics).
The intervention resulted in reductions in parent-reported screen time, sleep efficiency, night awakenings, and daytime sleep. The decrease in nap time was a surprise to the investigators.
These reductions were small. However, the investigators were most impressed (and I share in their sentiment) with the finding that 99% (104/105) of the families stayed with the study until completion, demonstrating that future studies using this format were highly feasible. The authors of the study were pleased also and possibly surprised that 94% (33/35) of the families who received the intervention adhered to the recommendations.
One Suggestion: ‘Just Shut the TV Off’
If you are a cynic, you might be tempted to explain the investigators’ (and my) excitement over the feasibility and adherence numbers as an attempt to pump up the importance of a set of otherwise lackluster numbers regarding sleep and the failure to find any association between the intervention and attention. However, having spent a large part of my career trying to encourage parents to improve their child’s sleep hygiene, often with little success, I am encouraged by this study’s success in getting families to accept and then adhere to the intervention.
I must admit that when presented with a child who appeared to be having some attention difficulties and was watching television as part of his or her bedtime ritual, there’s a good chance I would have simply told the parents, “Just shut the TV off.” This certainly worked with some families, particularly those who had already bought into my preaching about the importance of sleep. However, my acceptance and adherence rates were no where near the 99% and 94% these investigators where achieving.
I did try to make follow-up phone calls, as these investigators did, but generally only to the most seriously effected families or in situations in which felt I was going to have the greatest chance of success. I am sorry to say that I didn’t involve the parents in crafting my overly simplistic intervention. Had I been more open to parental input, I suspect my results would have improved.
An Alternative
I think another reason for these investigators’ success was the clever ploy of offering a replacement (in this case the bedtime box of alternative activities) when they asked the parents to remove the screen time. Getting anyone to break an unhealthy habit, be they parents or patients, it often helps to offer them an alternative. The activity may not be as appealing as their current behavior but it can fill the gap until a new even healthier behavior develops.
Building an efficient and effective bedtime ritual begins in the first months of life. The initial challenge could be separating nursing or a bottle from the settling in process. Later on it could mean helping a parent who is out of the home all day understand that they may have to suppress their natural urge to engage in vigorous play with his/her child at a time that is best devoted to winding down into a healthy bedtime ritual. Although screen time may not be physically stimulating, there is increasing evidence that it shouldn’t be part of a pre-bedtime ritual. The question of if and how it contributes to attention problems will have to wait until another day.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
For decades I have suspected that there is a strong association between sleep deprivation and pediatric attention disorders. More recently I have wondered whether screen time, particularly at bedtime might be a significant contributor to sleep quantity and quality in both children and adults. There is a growing body of research that combines my two observations and suggests that bedtime screen time through its effect on sleep may be linked to pediatric attention problems. However, most of this work is preliminary and needs to be confirmed.
Stumbling across a paper from England titled “Toddler Screen Use Before Bed and Its Effect on Sleep and Attention” renewed my hope that we finally have evidence to close that knowledge gap. My bubble burst quickly however when I jumped ahead and read the conclusion portion of the abstract and learned that authors observed “no clear difference in parent reported attention” in the group of children in which screen time before bedtime had been eliminated. The authors wonder if their small study sample may be to blame.
Disappointed, I persisted and read the paper in its entirety and found that despite their failure to link bedtime screen time with attention disorders, the investigators have made a significant contribution to our understanding of how we can better encourage good pediatric sleep hygiene.
The Study
One hundred and five families with a toddler who was being exposed to a video screen in the hour before bedtime were divided into three groups. One group received guidance and advice from a pediatric team about the potential benefit of eliminating bedtime screen time. They were also given a box of activities that contained “activity cards and age appropriate toys” to replace the screen use. The family also received periodic support and follow-up contacts. A second group received only the “bedtime box.” And the third received no intervention.
It is important to note that the investigators modeled their intervention on one developed in a previous study using older children that was “co-created with caregivers and early years practitioners”(my italics).
The intervention resulted in reductions in parent-reported screen time, sleep efficiency, night awakenings, and daytime sleep. The decrease in nap time was a surprise to the investigators.
These reductions were small. However, the investigators were most impressed (and I share in their sentiment) with the finding that 99% (104/105) of the families stayed with the study until completion, demonstrating that future studies using this format were highly feasible. The authors of the study were pleased also and possibly surprised that 94% (33/35) of the families who received the intervention adhered to the recommendations.
One Suggestion: ‘Just Shut the TV Off’
If you are a cynic, you might be tempted to explain the investigators’ (and my) excitement over the feasibility and adherence numbers as an attempt to pump up the importance of a set of otherwise lackluster numbers regarding sleep and the failure to find any association between the intervention and attention. However, having spent a large part of my career trying to encourage parents to improve their child’s sleep hygiene, often with little success, I am encouraged by this study’s success in getting families to accept and then adhere to the intervention.
I must admit that when presented with a child who appeared to be having some attention difficulties and was watching television as part of his or her bedtime ritual, there’s a good chance I would have simply told the parents, “Just shut the TV off.” This certainly worked with some families, particularly those who had already bought into my preaching about the importance of sleep. However, my acceptance and adherence rates were no where near the 99% and 94% these investigators where achieving.
I did try to make follow-up phone calls, as these investigators did, but generally only to the most seriously effected families or in situations in which felt I was going to have the greatest chance of success. I am sorry to say that I didn’t involve the parents in crafting my overly simplistic intervention. Had I been more open to parental input, I suspect my results would have improved.
An Alternative
I think another reason for these investigators’ success was the clever ploy of offering a replacement (in this case the bedtime box of alternative activities) when they asked the parents to remove the screen time. Getting anyone to break an unhealthy habit, be they parents or patients, it often helps to offer them an alternative. The activity may not be as appealing as their current behavior but it can fill the gap until a new even healthier behavior develops.
Building an efficient and effective bedtime ritual begins in the first months of life. The initial challenge could be separating nursing or a bottle from the settling in process. Later on it could mean helping a parent who is out of the home all day understand that they may have to suppress their natural urge to engage in vigorous play with his/her child at a time that is best devoted to winding down into a healthy bedtime ritual. Although screen time may not be physically stimulating, there is increasing evidence that it shouldn’t be part of a pre-bedtime ritual. The question of if and how it contributes to attention problems will have to wait until another day.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
For decades I have suspected that there is a strong association between sleep deprivation and pediatric attention disorders. More recently I have wondered whether screen time, particularly at bedtime might be a significant contributor to sleep quantity and quality in both children and adults. There is a growing body of research that combines my two observations and suggests that bedtime screen time through its effect on sleep may be linked to pediatric attention problems. However, most of this work is preliminary and needs to be confirmed.
Stumbling across a paper from England titled “Toddler Screen Use Before Bed and Its Effect on Sleep and Attention” renewed my hope that we finally have evidence to close that knowledge gap. My bubble burst quickly however when I jumped ahead and read the conclusion portion of the abstract and learned that authors observed “no clear difference in parent reported attention” in the group of children in which screen time before bedtime had been eliminated. The authors wonder if their small study sample may be to blame.
Disappointed, I persisted and read the paper in its entirety and found that despite their failure to link bedtime screen time with attention disorders, the investigators have made a significant contribution to our understanding of how we can better encourage good pediatric sleep hygiene.
The Study
One hundred and five families with a toddler who was being exposed to a video screen in the hour before bedtime were divided into three groups. One group received guidance and advice from a pediatric team about the potential benefit of eliminating bedtime screen time. They were also given a box of activities that contained “activity cards and age appropriate toys” to replace the screen use. The family also received periodic support and follow-up contacts. A second group received only the “bedtime box.” And the third received no intervention.
It is important to note that the investigators modeled their intervention on one developed in a previous study using older children that was “co-created with caregivers and early years practitioners”(my italics).
The intervention resulted in reductions in parent-reported screen time, sleep efficiency, night awakenings, and daytime sleep. The decrease in nap time was a surprise to the investigators.
These reductions were small. However, the investigators were most impressed (and I share in their sentiment) with the finding that 99% (104/105) of the families stayed with the study until completion, demonstrating that future studies using this format were highly feasible. The authors of the study were pleased also and possibly surprised that 94% (33/35) of the families who received the intervention adhered to the recommendations.
One Suggestion: ‘Just Shut the TV Off’
If you are a cynic, you might be tempted to explain the investigators’ (and my) excitement over the feasibility and adherence numbers as an attempt to pump up the importance of a set of otherwise lackluster numbers regarding sleep and the failure to find any association between the intervention and attention. However, having spent a large part of my career trying to encourage parents to improve their child’s sleep hygiene, often with little success, I am encouraged by this study’s success in getting families to accept and then adhere to the intervention.
I must admit that when presented with a child who appeared to be having some attention difficulties and was watching television as part of his or her bedtime ritual, there’s a good chance I would have simply told the parents, “Just shut the TV off.” This certainly worked with some families, particularly those who had already bought into my preaching about the importance of sleep. However, my acceptance and adherence rates were no where near the 99% and 94% these investigators where achieving.
I did try to make follow-up phone calls, as these investigators did, but generally only to the most seriously effected families or in situations in which felt I was going to have the greatest chance of success. I am sorry to say that I didn’t involve the parents in crafting my overly simplistic intervention. Had I been more open to parental input, I suspect my results would have improved.
An Alternative
I think another reason for these investigators’ success was the clever ploy of offering a replacement (in this case the bedtime box of alternative activities) when they asked the parents to remove the screen time. Getting anyone to break an unhealthy habit, be they parents or patients, it often helps to offer them an alternative. The activity may not be as appealing as their current behavior but it can fill the gap until a new even healthier behavior develops.
Building an efficient and effective bedtime ritual begins in the first months of life. The initial challenge could be separating nursing or a bottle from the settling in process. Later on it could mean helping a parent who is out of the home all day understand that they may have to suppress their natural urge to engage in vigorous play with his/her child at a time that is best devoted to winding down into a healthy bedtime ritual. Although screen time may not be physically stimulating, there is increasing evidence that it shouldn’t be part of a pre-bedtime ritual. The question of if and how it contributes to attention problems will have to wait until another day.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.
An Epidemiologist’s Guide to Debunking Nutritional Research
You’re invited to a dinner party but you struggle to make small talk. Do not worry; that will invariably crop up over cocktails. Because all journalism has been reduced to listicles, here are four ways to seem clever at dinner parties.
1. The Predinner Cocktails: A Lesson in Reverse Causation
Wine connoisseurs sniff, swirl, and gently swish the wine in their mouths before spitting out and cleansing their palates to better appreciate the subtlety of each vintage. If you’re not an oenophile, no matter. Whenever somebody claims that moderate amounts of alcohol are good for your heart, this is your moment to pounce. Interject yourself in the conversation and tell everybody about reverse causation.
Reverse causation, also known as protopathic bias, involves misinterpreting the directionality of an association. You assume that X leads to Y, when in fact Y leads to X. Temporal paradoxes are useful plot devices in science fiction movies, but they have no place in medical research. In our bland world, cause must precede effect. As such, smoking leads to lung cancer; lung cancer doesn’t make you smoke more.
But with alcohol, directionality is less obvious. Many studies of alcohol and cardiovascular disease have demonstrated a U-shaped association, with risk being lowest among those who drink moderate amounts of alcohol (usually one to two drinks per day) and higher in those who drink more and also those who drink very little.
But one must ask why some people drink little or no alcohol. There is an important difference between former drinkers and never drinkers. Former drinkers cut back for a reason. More likely than not, the reason for this newfound sobriety was medical. A new cancer diagnosis, the emergence of atrial fibrillation, the development of diabetes, or rising blood pressure are all good reasons to reduce or eliminate alcohol. A cross-sectional study will fail to capture that alcohol consumption changes over time — people who now don’t drink may have imbibed alcohol in years past. It was not abstinence that led to an increased risk for heart disease; it was the increased risk for heart disease that led to abstinence.
You see the same phenomenon with the so-called obesity paradox. The idea that being a little overweight is good for you may appeal when you no longer fit into last year’s pants. But people who are underweight are so for a reason. Malnutrition, cachexia from cancer, or some other cause is almost certainly driving up the risk at the left-hand side of the U-shaped curve that makes the middle part seem better than it actually is.
Food consumption changes over time. A cross-sectional survey at one point in time cannot accurately capture past habits and distant exposures, especially for diseases such as heart disease and cancer that develop slowly over time. Studies on alcohol that try to overcome these shortcomings by eliminating former drinkers, or by using Mendelian randomization to better account for past exposure, do not show a cardiovascular benefit for moderate red wine drinking.
2. The Hors D’oeuvres — The Importance of RCTs
Now that you have made yourself the center of attention, it is time to cement your newfound reputation as a font of scientific knowledge. Most self-respecting hosts will serve smoked salmon as an amuse-bouche before the main meal. When someone mentions the health benefits of fish oils, you should take the opportunity to teach them about confounding.
Fish, especially cold-water fish from northern climates, have relatively high amounts of omega-3 fatty acids. Despite the plethora of observational studies suggesting a cardiovascular benefit, it’s now relatively clear that fish oil or omega-3 supplements have no medical benefit.
This will probably come as a shock to the worried well, but many studies, including VITAL and ASCEND, have demonstrated no cardiovascular or cancer benefit to supplementation with omega-3s. The reason is straightforward and explains why hormone replacement therapy, vitamin D, and myriad purported game-changers never panned out. Confounding is hard to overcome in observational research.
Prior to the publication of the Women’s Health Initiative (WHI) Study, hormone replacement therapy was routinely prescribed to postmenopausal women because numerous observational studies suggested a cardiovascular benefit. But with the publication of the WHI study, it became clear that much of that “benefit” was due to confounding. The women choosing to take hormones were more health conscious at baseline and healthier overall.
A similar phenomenon occurred during COVID. Patients with low serum vitamin D levels had worse outcomes, prompting many to suggest vitamin D supplementation as a possible treatment. Trials did not support the intervention because we’d overlooked the obvious. People with vitamin D deficiency have underlying health problems that contribute to the vitamin D deficiency. They are probably older, frailer, possibly with a poorer diet. No amount of statistical adjustment can account for all those differences, and some degree of residual confounding will always persist.
The only way to overcome confounding is with randomization. When patients are randomly assigned to one group or another, their baseline differences largely balance out if the randomization was performed properly and the groups were large enough. There is a role for observational research, such as in situations where ethics, cost, and practicality do not allow for a randomized controlled trial. But randomized controlled trials have largely put to rest the purported health benefits of over-the-counter fish oils, omega-3s, and vitamin D.
3. The Main Course — Absolute vs Relative Risk
When you get to the main course, all eyes will now be on you. You will almost certainly be called upon to pronounce on the harms or benefits of red meat consumption. Begin by regaling your guests with a little trivia. Ask them if they know the definition of red meat and white meat. When someone says pork is white meat, you can reveal that “pork, the other white meat,” was a marketing slogan with no scientific underpinning. Now that everyone is lulled into a stupefied silence, tell them that red meat comes from mammals and white meat comes from birds. As they process this revelation, you can now launch into the deeply mathematical concept of absolute vs relative risk.
Many etiquette books will caution against bringing up math at a dinner party. These books are wrong. Everyone finds math interesting if they are primed properly. For example, you can point to a study claiming that berries reduce cardiovascular risk in women. Even if true — and there is reason to be cautious, given the observational nature of the research — we need to understand what the authors meant by a 32% risk reduction. (Side note: It was a reduction in hazard, with a hazard ratio of 0.68 (95% CI, 0.49-0.96), but we won’t dwell on the difference between hazard ratios and risk ratios right now.)
This relative risk reduction has to be interpreted carefully. The authors divided the population into quintiles based on their consumption of anthocyanins (the antioxidant in blueberries and strawberries) and compared the bottom fifth (average consumption, 2.5 mg/d) with the top fifth (average consumption, 25 mg/d). The bottom quintile had 126 myocardial infarctions (MIs) over 324,793 patient-years compared with 59 MIs over 332,143 patient-years. Some quick math shows an approximate reduction from 39 to 18 MIs per 100,000 patient-years. Or to put it another way, you must get 4762 women to increase their berry consumption 10-fold for 1 year to prevent one heart attack. Feel free to show people how you calculated this number. They will be impressed by your head for numbers. It is nothing more than 39 minus 18, divided by 100,000, to get the absolute risk reduction. Take the reciprocal of this (ie, 1 divided by this number) to get the number needed to treat.
Describing risks in absolute terms or using number needed to treat (or harm) can help conceptualize statistics that are sometimes hard to wrap your head around.
4. Dessert — Funding
By the time the coffee is served, everyone will be hanging on to your every word. This is as it should be, and you should not be afraid of your newfound power and influence.
Dessert will probably involve some form of chocolate, possibly in cake format. (Anyone who serves fruit as dessert is not someone you should associate with.) Take the opportunity to tell your follow diners that chocolate is not actually good for you and will not boost brain performance.
The health benefits of chocolate are often repeated but rarely scrutinized. In fact, much of the scientific research purporting to show that chocolate is good for you did not actually study chocolate. It usually involved a cocoa bean extract because the chocolate manufacturing process destroys the supposedly health-promoting antioxidants in the cocoa bean. It is true that dark chocolate has more antioxidants than milk chocolate, and that the addition of milk to chocolate further inactivates the potentially healthy antioxidants. But the amount of sugar and fat that has to be added to chocolate to make it palatable precludes any serious consideration about health benefits. Dark chocolate may have less fat and sugar than milk chocolate, but it still has a lot.
But even the cocoa bean extract doesn’t seem to do much for your heart or your brain. The long-awaited COSMOS study was published with surprisingly little fanfare. The largest randomized controlled trial of chocolate (or rather cocoa bean extract) was supposed to settle the issue definitively.
COSMOS showed no cardiovascular or neurocognitive benefit to the cocoa bean extract. But the health halo of chocolate continues to be bolstered by many studies funded by chocolate manufacturers.
We are appropriately critical of the pharmaceutical industry’s involvement in drug research. However, we should not forget that any private entity is prone to the same self-interest regardless of its product’s tastiness. How many of you knew that there was an avocado lobby funding research? No matter how many industry-funded observational studies using surrogate endpoints are out there telling you that chocolate is healthy, a randomized trial with hard clinical endpoints such as COSMOS should generally win the day.
The Final Goodbyes — Summarizing Your Case
As the party slowly winds down and everyone is saddened that you will soon take your leave, synthesize everything you have taught them over the evening. Like movies, not all studies are good. Some are just bad. They can be prone to reverse causation or confounding, and they may report relative risks when absolute risks would be more telling. Reading research studies critically is essential for separating the wheat from the chaff. With the knowledge you have now imparted to your friends, they will be much better consumers of medical news, especially when it comes to food.
And they will no doubt thank you for it by never inviting you to another dinner party!
Labos, a cardiologist at Hôpital, Notre-Dame, Montreal, Quebec, Canada, has disclosed no relevant financial relationships. He has a degree in epidemiology.
A version of this article appeared on Medscape.com.
You’re invited to a dinner party but you struggle to make small talk. Do not worry; that will invariably crop up over cocktails. Because all journalism has been reduced to listicles, here are four ways to seem clever at dinner parties.
1. The Predinner Cocktails: A Lesson in Reverse Causation
Wine connoisseurs sniff, swirl, and gently swish the wine in their mouths before spitting out and cleansing their palates to better appreciate the subtlety of each vintage. If you’re not an oenophile, no matter. Whenever somebody claims that moderate amounts of alcohol are good for your heart, this is your moment to pounce. Interject yourself in the conversation and tell everybody about reverse causation.
Reverse causation, also known as protopathic bias, involves misinterpreting the directionality of an association. You assume that X leads to Y, when in fact Y leads to X. Temporal paradoxes are useful plot devices in science fiction movies, but they have no place in medical research. In our bland world, cause must precede effect. As such, smoking leads to lung cancer; lung cancer doesn’t make you smoke more.
But with alcohol, directionality is less obvious. Many studies of alcohol and cardiovascular disease have demonstrated a U-shaped association, with risk being lowest among those who drink moderate amounts of alcohol (usually one to two drinks per day) and higher in those who drink more and also those who drink very little.
But one must ask why some people drink little or no alcohol. There is an important difference between former drinkers and never drinkers. Former drinkers cut back for a reason. More likely than not, the reason for this newfound sobriety was medical. A new cancer diagnosis, the emergence of atrial fibrillation, the development of diabetes, or rising blood pressure are all good reasons to reduce or eliminate alcohol. A cross-sectional study will fail to capture that alcohol consumption changes over time — people who now don’t drink may have imbibed alcohol in years past. It was not abstinence that led to an increased risk for heart disease; it was the increased risk for heart disease that led to abstinence.
You see the same phenomenon with the so-called obesity paradox. The idea that being a little overweight is good for you may appeal when you no longer fit into last year’s pants. But people who are underweight are so for a reason. Malnutrition, cachexia from cancer, or some other cause is almost certainly driving up the risk at the left-hand side of the U-shaped curve that makes the middle part seem better than it actually is.
Food consumption changes over time. A cross-sectional survey at one point in time cannot accurately capture past habits and distant exposures, especially for diseases such as heart disease and cancer that develop slowly over time. Studies on alcohol that try to overcome these shortcomings by eliminating former drinkers, or by using Mendelian randomization to better account for past exposure, do not show a cardiovascular benefit for moderate red wine drinking.
2. The Hors D’oeuvres — The Importance of RCTs
Now that you have made yourself the center of attention, it is time to cement your newfound reputation as a font of scientific knowledge. Most self-respecting hosts will serve smoked salmon as an amuse-bouche before the main meal. When someone mentions the health benefits of fish oils, you should take the opportunity to teach them about confounding.
Fish, especially cold-water fish from northern climates, have relatively high amounts of omega-3 fatty acids. Despite the plethora of observational studies suggesting a cardiovascular benefit, it’s now relatively clear that fish oil or omega-3 supplements have no medical benefit.
This will probably come as a shock to the worried well, but many studies, including VITAL and ASCEND, have demonstrated no cardiovascular or cancer benefit to supplementation with omega-3s. The reason is straightforward and explains why hormone replacement therapy, vitamin D, and myriad purported game-changers never panned out. Confounding is hard to overcome in observational research.
Prior to the publication of the Women’s Health Initiative (WHI) Study, hormone replacement therapy was routinely prescribed to postmenopausal women because numerous observational studies suggested a cardiovascular benefit. But with the publication of the WHI study, it became clear that much of that “benefit” was due to confounding. The women choosing to take hormones were more health conscious at baseline and healthier overall.
A similar phenomenon occurred during COVID. Patients with low serum vitamin D levels had worse outcomes, prompting many to suggest vitamin D supplementation as a possible treatment. Trials did not support the intervention because we’d overlooked the obvious. People with vitamin D deficiency have underlying health problems that contribute to the vitamin D deficiency. They are probably older, frailer, possibly with a poorer diet. No amount of statistical adjustment can account for all those differences, and some degree of residual confounding will always persist.
The only way to overcome confounding is with randomization. When patients are randomly assigned to one group or another, their baseline differences largely balance out if the randomization was performed properly and the groups were large enough. There is a role for observational research, such as in situations where ethics, cost, and practicality do not allow for a randomized controlled trial. But randomized controlled trials have largely put to rest the purported health benefits of over-the-counter fish oils, omega-3s, and vitamin D.
3. The Main Course — Absolute vs Relative Risk
When you get to the main course, all eyes will now be on you. You will almost certainly be called upon to pronounce on the harms or benefits of red meat consumption. Begin by regaling your guests with a little trivia. Ask them if they know the definition of red meat and white meat. When someone says pork is white meat, you can reveal that “pork, the other white meat,” was a marketing slogan with no scientific underpinning. Now that everyone is lulled into a stupefied silence, tell them that red meat comes from mammals and white meat comes from birds. As they process this revelation, you can now launch into the deeply mathematical concept of absolute vs relative risk.
Many etiquette books will caution against bringing up math at a dinner party. These books are wrong. Everyone finds math interesting if they are primed properly. For example, you can point to a study claiming that berries reduce cardiovascular risk in women. Even if true — and there is reason to be cautious, given the observational nature of the research — we need to understand what the authors meant by a 32% risk reduction. (Side note: It was a reduction in hazard, with a hazard ratio of 0.68 (95% CI, 0.49-0.96), but we won’t dwell on the difference between hazard ratios and risk ratios right now.)
This relative risk reduction has to be interpreted carefully. The authors divided the population into quintiles based on their consumption of anthocyanins (the antioxidant in blueberries and strawberries) and compared the bottom fifth (average consumption, 2.5 mg/d) with the top fifth (average consumption, 25 mg/d). The bottom quintile had 126 myocardial infarctions (MIs) over 324,793 patient-years compared with 59 MIs over 332,143 patient-years. Some quick math shows an approximate reduction from 39 to 18 MIs per 100,000 patient-years. Or to put it another way, you must get 4762 women to increase their berry consumption 10-fold for 1 year to prevent one heart attack. Feel free to show people how you calculated this number. They will be impressed by your head for numbers. It is nothing more than 39 minus 18, divided by 100,000, to get the absolute risk reduction. Take the reciprocal of this (ie, 1 divided by this number) to get the number needed to treat.
Describing risks in absolute terms or using number needed to treat (or harm) can help conceptualize statistics that are sometimes hard to wrap your head around.
4. Dessert — Funding
By the time the coffee is served, everyone will be hanging on to your every word. This is as it should be, and you should not be afraid of your newfound power and influence.
Dessert will probably involve some form of chocolate, possibly in cake format. (Anyone who serves fruit as dessert is not someone you should associate with.) Take the opportunity to tell your follow diners that chocolate is not actually good for you and will not boost brain performance.
The health benefits of chocolate are often repeated but rarely scrutinized. In fact, much of the scientific research purporting to show that chocolate is good for you did not actually study chocolate. It usually involved a cocoa bean extract because the chocolate manufacturing process destroys the supposedly health-promoting antioxidants in the cocoa bean. It is true that dark chocolate has more antioxidants than milk chocolate, and that the addition of milk to chocolate further inactivates the potentially healthy antioxidants. But the amount of sugar and fat that has to be added to chocolate to make it palatable precludes any serious consideration about health benefits. Dark chocolate may have less fat and sugar than milk chocolate, but it still has a lot.
But even the cocoa bean extract doesn’t seem to do much for your heart or your brain. The long-awaited COSMOS study was published with surprisingly little fanfare. The largest randomized controlled trial of chocolate (or rather cocoa bean extract) was supposed to settle the issue definitively.
COSMOS showed no cardiovascular or neurocognitive benefit to the cocoa bean extract. But the health halo of chocolate continues to be bolstered by many studies funded by chocolate manufacturers.
We are appropriately critical of the pharmaceutical industry’s involvement in drug research. However, we should not forget that any private entity is prone to the same self-interest regardless of its product’s tastiness. How many of you knew that there was an avocado lobby funding research? No matter how many industry-funded observational studies using surrogate endpoints are out there telling you that chocolate is healthy, a randomized trial with hard clinical endpoints such as COSMOS should generally win the day.
The Final Goodbyes — Summarizing Your Case
As the party slowly winds down and everyone is saddened that you will soon take your leave, synthesize everything you have taught them over the evening. Like movies, not all studies are good. Some are just bad. They can be prone to reverse causation or confounding, and they may report relative risks when absolute risks would be more telling. Reading research studies critically is essential for separating the wheat from the chaff. With the knowledge you have now imparted to your friends, they will be much better consumers of medical news, especially when it comes to food.
And they will no doubt thank you for it by never inviting you to another dinner party!
Labos, a cardiologist at Hôpital, Notre-Dame, Montreal, Quebec, Canada, has disclosed no relevant financial relationships. He has a degree in epidemiology.
A version of this article appeared on Medscape.com.
You’re invited to a dinner party but you struggle to make small talk. Do not worry; that will invariably crop up over cocktails. Because all journalism has been reduced to listicles, here are four ways to seem clever at dinner parties.
1. The Predinner Cocktails: A Lesson in Reverse Causation
Wine connoisseurs sniff, swirl, and gently swish the wine in their mouths before spitting out and cleansing their palates to better appreciate the subtlety of each vintage. If you’re not an oenophile, no matter. Whenever somebody claims that moderate amounts of alcohol are good for your heart, this is your moment to pounce. Interject yourself in the conversation and tell everybody about reverse causation.
Reverse causation, also known as protopathic bias, involves misinterpreting the directionality of an association. You assume that X leads to Y, when in fact Y leads to X. Temporal paradoxes are useful plot devices in science fiction movies, but they have no place in medical research. In our bland world, cause must precede effect. As such, smoking leads to lung cancer; lung cancer doesn’t make you smoke more.
But with alcohol, directionality is less obvious. Many studies of alcohol and cardiovascular disease have demonstrated a U-shaped association, with risk being lowest among those who drink moderate amounts of alcohol (usually one to two drinks per day) and higher in those who drink more and also those who drink very little.
But one must ask why some people drink little or no alcohol. There is an important difference between former drinkers and never drinkers. Former drinkers cut back for a reason. More likely than not, the reason for this newfound sobriety was medical. A new cancer diagnosis, the emergence of atrial fibrillation, the development of diabetes, or rising blood pressure are all good reasons to reduce or eliminate alcohol. A cross-sectional study will fail to capture that alcohol consumption changes over time — people who now don’t drink may have imbibed alcohol in years past. It was not abstinence that led to an increased risk for heart disease; it was the increased risk for heart disease that led to abstinence.
You see the same phenomenon with the so-called obesity paradox. The idea that being a little overweight is good for you may appeal when you no longer fit into last year’s pants. But people who are underweight are so for a reason. Malnutrition, cachexia from cancer, or some other cause is almost certainly driving up the risk at the left-hand side of the U-shaped curve that makes the middle part seem better than it actually is.
Food consumption changes over time. A cross-sectional survey at one point in time cannot accurately capture past habits and distant exposures, especially for diseases such as heart disease and cancer that develop slowly over time. Studies on alcohol that try to overcome these shortcomings by eliminating former drinkers, or by using Mendelian randomization to better account for past exposure, do not show a cardiovascular benefit for moderate red wine drinking.
2. The Hors D’oeuvres — The Importance of RCTs
Now that you have made yourself the center of attention, it is time to cement your newfound reputation as a font of scientific knowledge. Most self-respecting hosts will serve smoked salmon as an amuse-bouche before the main meal. When someone mentions the health benefits of fish oils, you should take the opportunity to teach them about confounding.
Fish, especially cold-water fish from northern climates, have relatively high amounts of omega-3 fatty acids. Despite the plethora of observational studies suggesting a cardiovascular benefit, it’s now relatively clear that fish oil or omega-3 supplements have no medical benefit.
This will probably come as a shock to the worried well, but many studies, including VITAL and ASCEND, have demonstrated no cardiovascular or cancer benefit to supplementation with omega-3s. The reason is straightforward and explains why hormone replacement therapy, vitamin D, and myriad purported game-changers never panned out. Confounding is hard to overcome in observational research.
Prior to the publication of the Women’s Health Initiative (WHI) Study, hormone replacement therapy was routinely prescribed to postmenopausal women because numerous observational studies suggested a cardiovascular benefit. But with the publication of the WHI study, it became clear that much of that “benefit” was due to confounding. The women choosing to take hormones were more health conscious at baseline and healthier overall.
A similar phenomenon occurred during COVID. Patients with low serum vitamin D levels had worse outcomes, prompting many to suggest vitamin D supplementation as a possible treatment. Trials did not support the intervention because we’d overlooked the obvious. People with vitamin D deficiency have underlying health problems that contribute to the vitamin D deficiency. They are probably older, frailer, possibly with a poorer diet. No amount of statistical adjustment can account for all those differences, and some degree of residual confounding will always persist.
The only way to overcome confounding is with randomization. When patients are randomly assigned to one group or another, their baseline differences largely balance out if the randomization was performed properly and the groups were large enough. There is a role for observational research, such as in situations where ethics, cost, and practicality do not allow for a randomized controlled trial. But randomized controlled trials have largely put to rest the purported health benefits of over-the-counter fish oils, omega-3s, and vitamin D.
3. The Main Course — Absolute vs Relative Risk
When you get to the main course, all eyes will now be on you. You will almost certainly be called upon to pronounce on the harms or benefits of red meat consumption. Begin by regaling your guests with a little trivia. Ask them if they know the definition of red meat and white meat. When someone says pork is white meat, you can reveal that “pork, the other white meat,” was a marketing slogan with no scientific underpinning. Now that everyone is lulled into a stupefied silence, tell them that red meat comes from mammals and white meat comes from birds. As they process this revelation, you can now launch into the deeply mathematical concept of absolute vs relative risk.
Many etiquette books will caution against bringing up math at a dinner party. These books are wrong. Everyone finds math interesting if they are primed properly. For example, you can point to a study claiming that berries reduce cardiovascular risk in women. Even if true — and there is reason to be cautious, given the observational nature of the research — we need to understand what the authors meant by a 32% risk reduction. (Side note: It was a reduction in hazard, with a hazard ratio of 0.68 (95% CI, 0.49-0.96), but we won’t dwell on the difference between hazard ratios and risk ratios right now.)
This relative risk reduction has to be interpreted carefully. The authors divided the population into quintiles based on their consumption of anthocyanins (the antioxidant in blueberries and strawberries) and compared the bottom fifth (average consumption, 2.5 mg/d) with the top fifth (average consumption, 25 mg/d). The bottom quintile had 126 myocardial infarctions (MIs) over 324,793 patient-years compared with 59 MIs over 332,143 patient-years. Some quick math shows an approximate reduction from 39 to 18 MIs per 100,000 patient-years. Or to put it another way, you must get 4762 women to increase their berry consumption 10-fold for 1 year to prevent one heart attack. Feel free to show people how you calculated this number. They will be impressed by your head for numbers. It is nothing more than 39 minus 18, divided by 100,000, to get the absolute risk reduction. Take the reciprocal of this (ie, 1 divided by this number) to get the number needed to treat.
Describing risks in absolute terms or using number needed to treat (or harm) can help conceptualize statistics that are sometimes hard to wrap your head around.
4. Dessert — Funding
By the time the coffee is served, everyone will be hanging on to your every word. This is as it should be, and you should not be afraid of your newfound power and influence.
Dessert will probably involve some form of chocolate, possibly in cake format. (Anyone who serves fruit as dessert is not someone you should associate with.) Take the opportunity to tell your follow diners that chocolate is not actually good for you and will not boost brain performance.
The health benefits of chocolate are often repeated but rarely scrutinized. In fact, much of the scientific research purporting to show that chocolate is good for you did not actually study chocolate. It usually involved a cocoa bean extract because the chocolate manufacturing process destroys the supposedly health-promoting antioxidants in the cocoa bean. It is true that dark chocolate has more antioxidants than milk chocolate, and that the addition of milk to chocolate further inactivates the potentially healthy antioxidants. But the amount of sugar and fat that has to be added to chocolate to make it palatable precludes any serious consideration about health benefits. Dark chocolate may have less fat and sugar than milk chocolate, but it still has a lot.
But even the cocoa bean extract doesn’t seem to do much for your heart or your brain. The long-awaited COSMOS study was published with surprisingly little fanfare. The largest randomized controlled trial of chocolate (or rather cocoa bean extract) was supposed to settle the issue definitively.
COSMOS showed no cardiovascular or neurocognitive benefit to the cocoa bean extract. But the health halo of chocolate continues to be bolstered by many studies funded by chocolate manufacturers.
We are appropriately critical of the pharmaceutical industry’s involvement in drug research. However, we should not forget that any private entity is prone to the same self-interest regardless of its product’s tastiness. How many of you knew that there was an avocado lobby funding research? No matter how many industry-funded observational studies using surrogate endpoints are out there telling you that chocolate is healthy, a randomized trial with hard clinical endpoints such as COSMOS should generally win the day.
The Final Goodbyes — Summarizing Your Case
As the party slowly winds down and everyone is saddened that you will soon take your leave, synthesize everything you have taught them over the evening. Like movies, not all studies are good. Some are just bad. They can be prone to reverse causation or confounding, and they may report relative risks when absolute risks would be more telling. Reading research studies critically is essential for separating the wheat from the chaff. With the knowledge you have now imparted to your friends, they will be much better consumers of medical news, especially when it comes to food.
And they will no doubt thank you for it by never inviting you to another dinner party!
Labos, a cardiologist at Hôpital, Notre-Dame, Montreal, Quebec, Canada, has disclosed no relevant financial relationships. He has a degree in epidemiology.
A version of this article appeared on Medscape.com.
8 New GI Studies With Practice-Shifting Implications
I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.
In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations.
Performing Capsule Endoscopy in Patients Taking GLP-1s
We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.
In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.
Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).
Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01).
We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs.
Barrett Esophagus On the Rise in the Young
The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).
This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups.
Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group.
Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.
Results also showed that 6% of those with young-onset BE had BE-related neoplasia.
ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE.
We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors.
There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker.
Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.
A Novel Biologic for Eosinophilic Esophagitis
The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).
Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE.
The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks.
There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups.
I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.
No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation
Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.
Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose.
Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment.
Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03).
In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT.
Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis
Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August.
Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis.
Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.
Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.
The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis.
Advantages to Respiratory Syncytial Virus Vaccination in IBD
Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD.
Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently.
Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not.
Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk.
For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services.
This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.
I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.
The Impact of Palliative Care Consultations in Decompensated Cirrhosis
The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.
Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis.
Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).
The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.
Auxora: A Novel Treatment for Acute Pancreatitis
The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.
There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).
Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure.
The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.
This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days.
The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation.
The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement.
There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure.
The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.
Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them.
Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.
A version of this article first appeared on Medscape.com.
I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.
In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations.
Performing Capsule Endoscopy in Patients Taking GLP-1s
We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.
In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.
Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).
Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01).
We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs.
Barrett Esophagus On the Rise in the Young
The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).
This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups.
Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group.
Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.
Results also showed that 6% of those with young-onset BE had BE-related neoplasia.
ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE.
We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors.
There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker.
Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.
A Novel Biologic for Eosinophilic Esophagitis
The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).
Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE.
The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks.
There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups.
I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.
No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation
Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.
Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose.
Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment.
Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03).
In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT.
Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis
Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August.
Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis.
Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.
Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.
The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis.
Advantages to Respiratory Syncytial Virus Vaccination in IBD
Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD.
Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently.
Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not.
Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk.
For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services.
This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.
I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.
The Impact of Palliative Care Consultations in Decompensated Cirrhosis
The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.
Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis.
Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).
The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.
Auxora: A Novel Treatment for Acute Pancreatitis
The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.
There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).
Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure.
The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.
This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days.
The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation.
The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement.
There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure.
The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.
Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them.
Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.
A version of this article first appeared on Medscape.com.
I’m just back from the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting in Philadelphia, Pennsylvania.
In part 2 of this series, I’m offering my highlights from this year’s meeting. (Part 1 is available here.) They are not presented in any particular order, but instead I am sharing what I found to be the most exciting among the thousands of abstracts and presentations.
Performing Capsule Endoscopy in Patients Taking GLP-1s
We’ve heard a lot about glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and the possibility that they might contribute to an increased risk for retained gastric contents and aspiration during endoscopy.
In the first study I’d like to highlight, researchers from the Mayo Clinic in Jacksonville, Florida, investigated video capsule endoscopy in patients with diabetes who were taking GLP-1 RAs vs a control group with diabetes not taking GLP-1 Ras. Patients in this retrospective matched cohort study were well balanced for demographics and diabetes-related characteristics.
Researchers found that in 7% of the 68 patients in the GLP-1 RA cohort, the video capsule endoscopy actually failed to pass through the stomach, whereas it passed successfully in all 68 patients in the control group (P =.06). The GLP-1 RA cohort had a longer transit time by a factor of almost four times (P <.001).
Multivariate analysis also showed that gastric transit time was approximately 80 minutes longer in the GLP-1 RA cohort (P <.001). Interestingly, 23.5% (16 of 68 patients) in the GLP-1 RA group experienced incomplete passage of the video capsule endoscopy through the small intestine, which was significantly higher than the proportion observed in the control group (4.4%; P <.01).
We need to look at potential strategies to mitigate these effects. Be aware of these results as you perform capsule endoscopy in patients taking GLP-1 RAs.
Barrett Esophagus On the Rise in the Young
The second study that caught my eye revealed the increasing incidence of young-onset Barrett esophagus (BE).
This population-based study used data obtained from TriNetX, a multi-institutional national database that offers a composite of health records from 88 healthcare organizations. Eligible patients had to have a negative upper esophagogastroduodenoscopy for BE prior to subsequently developing BE. Researchers stratified patients as to whether they were younger (< 50 years) or older (≥ 50 years), with further age ranges analyzed within those groups.
Young-onset BE accounted for 20% of all incident cases. The majority (94%) had nondysplastic BE. The incidence rate was not significantly different depending on whether patients were in the 45- to 49-year or 50- to 54-year age group.
Regression analysis revealed that there was a significantly increased trend for young-onset BE with hiatal hernia (odds ratio [OR], 2.6), smoking (OR, 2.3), White race (OR, 2.3), obstructive sleep apnea (OR, 2.2), male gender (OR, 2.0), and — at relatively lower risk levels — gastroesophageal reflux disease symptoms (OR, 1.2) and body mass index (OR, 1.1). The researchers did not analyze patients based on the presence of obesity, which is one of the risk factors for BE mentioned in national guidelines.
Results also showed that 6% of those with young-onset BE had BE-related neoplasia.
ACG guidelines recommend screening for BE beginning at age 50 in those with some of the risk factors noted in this study, including the presence of chronic gastroesophageal reflux disease symptoms. However, doing so may not capture the growing number of patients with young-onset BE.
We’ve seen a similar rise in rates of young-onset colorectal cancer, which has caused us to reevaluate our screening methods. Maybe we should do this for BE as well, specifically for patients presenting with these risk factors.
There’s a caveat to be aware of, which comes from my personal experience. I was biopsied for short-segment BE, and because it came up on my health record, it increased my life insurance premiums. This was because I was identified as having the risk profile of, essentially, an otherwise healthy smoker.
Dr Nicholas J. Shaheen and colleagues published a study several years ago showing that many insurance companies would not certify young, otherwise healthy people once diagnosed with BE. This is something to be aware of when you start to screen for BE, especially among younger patients.
A Novel Biologic for Eosinophilic Esophagitis
The next study presented results from a randomized, placebo-controlled, phase 3 study of cendakimab, a biologic agent in development for the treatment of eosinophilic esophagitis (EoE).
Dupilumab, which is an anti–interleukin (IL)-4 antibody, is the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of EoE. Cendakimab, in turn, is a monoclonal antibody that neutralizes IL-13, a cytokine that plays a key role in EoE.
The study was led by Dr Evan Dellon from the University of North Carolina at Chapel Hill. Dellon and colleagues analyzed two different dosing regimens of cendakimab — 360 mg once weekly for 48 weeks, or 360 mg once weekly for 24 weeks followed by 360 mg every other week for 24 weeks — vs placebo for 48 weeks.
There was a significant effect for both cendakimab regimens in terms of symptom improvement and histologic response. There wasn’t much difference between participants that maintained once-weekly dosing and those who switched over to receive cendakimab every other week at 24 weeks. Only a minimal number of serious adverse events leading to discontinuation were noted in the study, with no notable difference between the treatment groups.
I think we’ll probably see this drug become available to us soon after it goes through the FDA review process, at which point it will add to our ability to use formative biologics in patients with EoE.
No Clear Benefit to Adding Bezlotoxumab to Fecal Microbiota Transplantation
Next was a very interesting study, and I think a clinically relevant one, about using fecal microbiota transplantation (FMT) alone or in combination with bezlotoxumab in patients with inflammatory bowel disease (IBD) with recurrent Clostridioides difficile infection.
Bezlotoxumab is a fully human monoclonal antibody that binds to C difficile toxin B. This drug has been studied and is approved for use, but it’s also extremely expensive, at a cost of approximately $4000 per dose.
Patients with IBD were eligible for inclusion if they had had two or more episodes of C difficile infection. They were then randomized in a 1:1 ration to receive either a single infusion of bezlotoxumab or placebo prior to FMT. The primary endpoint was C difficile infection recurrence within 8 weeks, which was defined as diarrhea plus a positive enzyme immunoassay toxin test. The secondary outcome was C difficile decolonization following treatment.
Researchers observed no statistically significant difference between the two cohorts. Steroid use prior to FMT significantly increased the risk for ongoing C difficile colonization (P =.03).
In summary, this is a case where it doesn’t seem that more is better. Bezlotoxumab didn’t add much, which calls into question the justification for its combined use with FMT.
Additional Positive Data for Seladelpar in Primary Biliary Cholangitis and Cirrhosis
Reassuring findings were presented on seladelpar, which was granted accelerated approval by the FDA in August.
Seladelpar is a selective peroxisome proliferator–activated receptor delta agonist that works in biliary cholangitis by regulating the genes involved in blocking biliary bile acid synthesis and controlling inflammation and fibrosis.
Results from the phase 3 RESPONSE trial were published in The New England Journal of Medicine in February reporting on the use of seladelpar in primary biliary cholangitis.
Whereas the RESPONSE trial removed decompensated patients, the ongoing phase 3 ASSURE trial results presented at this year’s meeting included patients with compensated cirrhosis. Approximately 94% of the patients in this study had Child-Pugh class A and 6% had class B cirrhosis. Eligibility required that patients had an inadequate response or were intolerant to ursodeoxycholic acid. Patients were administered open-label seladelpar 10 mg orally daily and followed for up to 1 year.
The good news is that there were no safety signals, which is reassuring news for our patients with compensated cirrhosis.
Advantages to Respiratory Syncytial Virus Vaccination in IBD
Another study that offered results certainly worthy of attention dealt with vaccination recommendations in patients with IBD.
Vaccination for respiratory syncytial virus (RSV) is now available in the United States. Its use was recommended for patients with IBD as early as 2021 per the Canadian Association of Gastroenterology’s clinical practice guideline, which discusses both live and nonlive vaccines. We should be aggressive in recommending this vaccine to our patients with IBD, but we haven’t really had one until recently.
Researchers behind this retrospective cohort study used the TriNetX database, which includes over 100 million unique patient charts. They identified patients with IBD, who were then divided into two groups according to whether they received the RSV vaccine or not.
Although this analysis was conducted in patients > 60 years of age, the US Centers for Disease Control and Prevention recommends RSV vaccination for all those over the age of 75 years, as well as for those 60-74 years old based on severity of risk.
For the primary endpoint of risk for RSV pneumonia, the OR was dramatically better in those who were vaccinated, with an approximately 80% risk reduction. Additionally, vaccinated patients experienced risk reductions of approximately 60% for acute respiratory failure, 50% for hospital inpatient admission, and 70% for requiring intensive care unit services.
This is a strong study showing not only that RSV vaccine did not exacerbate IBD but also that it improved outcomes in these patients. There’s a live-attenuated RSV vaccination that’s administered intranasally, which wouldn’t be used in your biologic or immunosuppressed patients with IBD, but the intramuscularly administered RSV vaccine doesn’t have any risk.
I think we can immediately begin recommending the RSV vaccine for our patients with IBD, particularly in those 60 years of age or older.
The Impact of Palliative Care Consultations in Decompensated Cirrhosis
The next study I’d like to highlight offers important data on the impact of palliative care consultation on 30- and 90-day readmission in patients with decompensated cirrhosis, which is a major cause of morbidity and mortality.
Researchers queried the National Readmissions Database over a 10-year period (2010-2019) to determine whether patients received a palliative care consult during index admission. They drew on a population of over 1.6 million patients admitted with decompensated cirrhosis.
Of this group, only 7.4% received a palliative care consultation at the index admission. But if they had this consultation, it was associated with a dramatic effect on readmission at 30 and 90 days. There was statistically significant risk reduction of approximately 70% for both 30- and 90-day readmission compared with those who didn’t receive the palliative consult (P <.001).
The take-home message here is to get a palliative care consult with these patients when they come in. Your hospital will unquestionably experience value in this reduction in readmission, especially considering that readmission within 30 days may not even be covered. Look at these results and start to take advantage of this valuable consultation.
Auxora: A Novel Treatment for Acute Pancreatitis
The last study for discussion offered very interesting data related to a drug called Auxora, a calcium release–activated calcium-channel inhibitor.
There is growing data that overactive calcium release–activated calcium channels aggravate acute pancreatitis and accelerate systemic inflammatory response syndrome (SIRS).
Acute pancreatitis with necrosis encompasses both local and systemic inflammation and is associated with significant mortality and morbidity. It is estimated that among patients with acute pancreatitis, 20%-30% have pancreatic necrosis, 30% develop infection, and 25% develop organ failure.
The presence of SIRS seems to herald the activation of these complex inflammatory pathways, which then leads to organ failure and necrosis, which can potentially be stemmed through this calcium channel inhibitor. Phase 2 studies of Auxora found that its use was associated with significant reduction in the risk for progression.
This subsequent phase 3 study looked at patients with acute pancreatitis and accompanying grade ≥ 2 SIRS criteria. They were randomized to receive placebo or Auxora at doses of 2 mg/kg, 1 mg/kg, or 0.5 mg/kg, which was administered intravenously over 4 hours for 3 consecutive days.
The primary endpoint was time to solid food tolerance, which was defined as eating ≥ 50% of a ≥ 500-calorie low-fat solid meal without increased abdominal pain or emesis, which is an important target because we always aim for enteral nutrition in patients with acute pancreatitis. The key secondary endpoint was severe respiratory failure, which was defined as invasive mechanical ventilation or ≥ 48 hours of either high-flow nasal cannula or noninvasive mechanical ventilation.
The primary endpoint was dramatically improved among those receiving Auxora, who achieved early onset of refeed. It appears that the high-dose 2 mg/kg may be the most beneficial in achieving improvement.
There were no patients with suspected or unexpected adverse events in the study population. Additionally, no patients receiving Auxora at any dose level went on to develop respiratory failure.
The present results show that Auxora decreases the time for solid food tolerance, as well as the rates of respiratory failure and necrotizing pancreatitis in patients presenting with two or more SIRS criteria. We’ll certainly look forward to more data, but it provides hope for a new treatment for acute pancreatitis.
Some of the take-home messages I presented are actionable now, whereas for others, we’ll have to wait and see what the final data show as well as the results of ongoing FDA approval before applying them.
Dr Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. He reported serving in an advisory position with ISOTHRIVE. This transcript has been edited for clarity.
A version of this article first appeared on Medscape.com.