Commentary

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 [email protected].

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 [email protected].

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 [email protected].

You’re invited to a dinner party but you struggle to make small talk. Do not worry; you can use your knowledge of study design and epidemiology to impress people with your savoir faire regarding popular food myths 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; you can use your knowledge of study design and epidemiology to impress people with your savoir faire regarding popular food myths 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; you can use your knowledge of study design and epidemiology to impress people with your savoir faire regarding popular food myths 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.

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.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

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.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

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.

There were lots of intriguing data presented at ACG 2024. Obviously, we’d like to see them evolve in subsequent journal manuscripts. 

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.

This transcript has been edited for clarity.

In this podcast, I’m going to talk about unexplained high platelet counts, or thrombocytosis, and the risk for cancer in primary care. Let’s start with a typical case we all might see in primary care.

Louisa is 47 years old and is the chief financial officer for a tech startup company. She presents to us in primary care feeling tired all the time — a very common presentation in primary care — with associated reduced appetite. Past medical history includes irritable bowel syndrome, and she’s an ex-smoker.

Systemic inquiry is unremarkable. Specifically, there is no history of weight loss. Louisa has not been prescribed any medication and uses over-the-counter remedies for her irritable bowel syndrome. Examination is also unremarkable. Blood tests were checked, which were all reassuring, except for a platelet count of 612 × 10⁹ cells/L (usual normal range, about 150-450).

What do we do next? Do we refer for an urgent chest x-ray to exclude lung cancer? Do we check a quantitative immunohistochemical fecal occult blood test (qFIT) to identify any occult bleeding in her stool? Do we refer for a routine upper gastrointestinal endoscopy or pelvic ultrasound scan to exclude any upper gastrointestinal or endometrial malignancy?

Do we simply repeat the bloods? If so, do we repeat them routinely or urgently, and indeed, which ones should we recheck?

Louisa has an unexplained thrombocytosis. How do we manage this in primary care? Thrombocytosis is generally defined as a raised platelet count over 450. Importantly, thrombocytosis is a common incidental finding in around 2% of those over 40 years of age attending primary care. Reassuringly, 80%-90% of thrombocytosis is reactive, secondary to acute blood loss, infection, or inflammation, and the majority of cases resolve within 3 months.

Why the concern with Louisa then? Although most cases are reactive, clinical guidance (for example, NICE suspected cancer guidance in the UK and Scottish suspected cancer guidance in Scotland) reminds us that unexplained thrombocytosis is a risk marker for some solid-tumor malignancies.

Previous studies have demonstrated that unexplained thrombocytosis is associated with a 1-year cancer incidence of 11.6% in males and 6.2% in females, well exceeding the standard 3% threshold warranting investigation for underlying malignancy. However, thrombocytosis should not be used as a stand-alone diagnostic or screening test for cancer, or indeed to rule out cancer.

Instead, unexplained thrombocytosis should prompt us to think cancer. The Scottish suspected cancer referral guidelines include thrombocytosis in the investigation criteria for what they call the LEGO-C cancers — L for lung, E for endometrial, G for gastric, O for oesophageal, and C for colorectal, which is a useful reminder for us all.

What further history, examination, and investigations might we consider in primary care if we identify an unexplained high platelet count? As always, we should use our clinical judgment and trust our clinical acumen.

We should consider all the possible underlying causes, including infection, inflammation, and blood loss, including menstrual blood loss in women; myeloproliferative disorders such as polycythemia rubra vera, chronic myeloid leukemia, and essential thrombocythemia; and, of course, underlying malignancy. If a likely underlying reversible cause is present (for example, a recent lower respiratory tract infection), simply repeating the full blood count in 4-6 weeks is quite appropriate to see if the thrombocytosis has resolved.

Remember, 80%-90% of cases are reactive thrombocytosis, and most cases resolve within 3 months. If thrombocytosis is unexplained or not resolving, consider checking ferritin levels to exclude iron deficiency. Consider checking C-reactive protein (CRP) levels to exclude any inflammation, and also consider checking a blood film to exclude any hematologic disorders, in addition, of course, to more detailed history-taking and examination to elicit any red flags.

We can also consider a JAK2 gene mutation test, if it is available to you locally, or a hematology referral if we suspect a myeloproliferative disorder. JAK2 is a genetic mutation that may be present in people with essential thrombocythemia and can indicate a diagnosis of polycythemia rubra vera.

Subsequent to this, and again using our clinical judgment, we then need to exclude the LEGO-C cancers. Consider urgent chest x-ray to exclude lung cancer or pelvic ultrasound in women to exclude endometrial cancer. Also, we should consider an upper gastrointestinal endoscopy, particularly in those individuals who have associated upper gastrointestinal symptoms and/or weight loss.

Finally, consider a qFIT to identify any occult bleeding in the stool, again if it’s available to you, or certainly if not, urgent lower gastrointestinal investigations to exclude colorectal cancer.

Alongside these possible investigations, as always, we should safety-net appropriately within agreed timeframes and check for resolution of the thrombocytosis according to the condition being suspected. Remember, most cases resolve within 3 months.

Returning to Louisa, what did I do? After seeing a platelet count of 600, I subsequently telephoned her and reexplored her history, which yielded nil else of note. Specifically, there was no history of unexplained weight loss, no history of upper or lower gastrointestinal symptoms, and certainly nothing significantly different from her usual irritable bowel syndrome symptoms. There were also no respiratory or genitourinary symptoms of note.

I did arrange for Louisa to undergo a chest x-ray over the next few days, though, as she was an ex-smoker. This was subsequently reported as normal. I appreciate chest x-rays have poor sensitivity for detecting lung cancer, as highlighted in a number of recent papers, but it was mutually agreed with Louisa that we would simply repeat her blood test in around 6 weeks. As well as repeating the full blood count, I arranged to check her ferritin, CRP, and a blood film, and then I was planning to reassess her clinically in person.

These bloods and my subsequent clinical review were reassuring. In fact, her platelet count had normalized after that 6 weeks had elapsed. Her thrombocytosis had resolved.

I didn’t arrange any further follow-up for her, but I did give her the usual safety netting advice to re-present to me or one of my colleagues if she does develop any worrying symptoms or signs.

I appreciate these scenarios are not always this straightforward, but I wanted to outline what investigations and referrals we may need to consider in primary care if we encounter an unexplained high platelet count.

There are a couple of quality-improvement activities for us all to consider in primary care. Consider as a team how we would respond to an incidental finding of thrombocytosis on a full blood count. Also consider what are our safety-netting options for those found to have raised platelet counts but no other symptoms or risk factors for underlying malignancy.

Finally, I’ve produced a Medscape UK primary care hack or clinical aide-memoire on managing unexplained thrombocytosis and associated cancer risk in primary care for all healthcare professionals working in primary care. This can be found online. I hope you find this resource helpful.

Dr. Kevin Fernando, General practitioner partner with specialist interests in cardiovascular, renal, and metabolic medicine, North Berwick Group Practice in Scotland, has disclosed relevant financial relationships with Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Lilly, Menarini, Novartis, Novo Nordisk, Roche Diagnostics, Embecta, Roche Diabetes Care, Sanofi Menarini, and Daiichi Sankyo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

In this podcast, I’m going to talk about unexplained high platelet counts, or thrombocytosis, and the risk for cancer in primary care. Let’s start with a typical case we all might see in primary care.

Louisa is 47 years old and is the chief financial officer for a tech startup company. She presents to us in primary care feeling tired all the time — a very common presentation in primary care — with associated reduced appetite. Past medical history includes irritable bowel syndrome, and she’s an ex-smoker.

Systemic inquiry is unremarkable. Specifically, there is no history of weight loss. Louisa has not been prescribed any medication and uses over-the-counter remedies for her irritable bowel syndrome. Examination is also unremarkable. Blood tests were checked, which were all reassuring, except for a platelet count of 612 × 10⁹ cells/L (usual normal range, about 150-450).

What do we do next? Do we refer for an urgent chest x-ray to exclude lung cancer? Do we check a quantitative immunohistochemical fecal occult blood test (qFIT) to identify any occult bleeding in her stool? Do we refer for a routine upper gastrointestinal endoscopy or pelvic ultrasound scan to exclude any upper gastrointestinal or endometrial malignancy?

Do we simply repeat the bloods? If so, do we repeat them routinely or urgently, and indeed, which ones should we recheck?

Louisa has an unexplained thrombocytosis. How do we manage this in primary care? Thrombocytosis is generally defined as a raised platelet count over 450. Importantly, thrombocytosis is a common incidental finding in around 2% of those over 40 years of age attending primary care. Reassuringly, 80%-90% of thrombocytosis is reactive, secondary to acute blood loss, infection, or inflammation, and the majority of cases resolve within 3 months.

Why the concern with Louisa then? Although most cases are reactive, clinical guidance (for example, NICE suspected cancer guidance in the UK and Scottish suspected cancer guidance in Scotland) reminds us that unexplained thrombocytosis is a risk marker for some solid-tumor malignancies.

Previous studies have demonstrated that unexplained thrombocytosis is associated with a 1-year cancer incidence of 11.6% in males and 6.2% in females, well exceeding the standard 3% threshold warranting investigation for underlying malignancy. However, thrombocytosis should not be used as a stand-alone diagnostic or screening test for cancer, or indeed to rule out cancer.

Instead, unexplained thrombocytosis should prompt us to think cancer. The Scottish suspected cancer referral guidelines include thrombocytosis in the investigation criteria for what they call the LEGO-C cancers — L for lung, E for endometrial, G for gastric, O for oesophageal, and C for colorectal, which is a useful reminder for us all.

What further history, examination, and investigations might we consider in primary care if we identify an unexplained high platelet count? As always, we should use our clinical judgment and trust our clinical acumen.

We should consider all the possible underlying causes, including infection, inflammation, and blood loss, including menstrual blood loss in women; myeloproliferative disorders such as polycythemia rubra vera, chronic myeloid leukemia, and essential thrombocythemia; and, of course, underlying malignancy. If a likely underlying reversible cause is present (for example, a recent lower respiratory tract infection), simply repeating the full blood count in 4-6 weeks is quite appropriate to see if the thrombocytosis has resolved.

Remember, 80%-90% of cases are reactive thrombocytosis, and most cases resolve within 3 months. If thrombocytosis is unexplained or not resolving, consider checking ferritin levels to exclude iron deficiency. Consider checking C-reactive protein (CRP) levels to exclude any inflammation, and also consider checking a blood film to exclude any hematologic disorders, in addition, of course, to more detailed history-taking and examination to elicit any red flags.

We can also consider a JAK2 gene mutation test, if it is available to you locally, or a hematology referral if we suspect a myeloproliferative disorder. JAK2 is a genetic mutation that may be present in people with essential thrombocythemia and can indicate a diagnosis of polycythemia rubra vera.

Subsequent to this, and again using our clinical judgment, we then need to exclude the LEGO-C cancers. Consider urgent chest x-ray to exclude lung cancer or pelvic ultrasound in women to exclude endometrial cancer. Also, we should consider an upper gastrointestinal endoscopy, particularly in those individuals who have associated upper gastrointestinal symptoms and/or weight loss.

Finally, consider a qFIT to identify any occult bleeding in the stool, again if it’s available to you, or certainly if not, urgent lower gastrointestinal investigations to exclude colorectal cancer.

Alongside these possible investigations, as always, we should safety-net appropriately within agreed timeframes and check for resolution of the thrombocytosis according to the condition being suspected. Remember, most cases resolve within 3 months.

Returning to Louisa, what did I do? After seeing a platelet count of 600, I subsequently telephoned her and reexplored her history, which yielded nil else of note. Specifically, there was no history of unexplained weight loss, no history of upper or lower gastrointestinal symptoms, and certainly nothing significantly different from her usual irritable bowel syndrome symptoms. There were also no respiratory or genitourinary symptoms of note.

I did arrange for Louisa to undergo a chest x-ray over the next few days, though, as she was an ex-smoker. This was subsequently reported as normal. I appreciate chest x-rays have poor sensitivity for detecting lung cancer, as highlighted in a number of recent papers, but it was mutually agreed with Louisa that we would simply repeat her blood test in around 6 weeks. As well as repeating the full blood count, I arranged to check her ferritin, CRP, and a blood film, and then I was planning to reassess her clinically in person.

These bloods and my subsequent clinical review were reassuring. In fact, her platelet count had normalized after that 6 weeks had elapsed. Her thrombocytosis had resolved.

I didn’t arrange any further follow-up for her, but I did give her the usual safety netting advice to re-present to me or one of my colleagues if she does develop any worrying symptoms or signs.

I appreciate these scenarios are not always this straightforward, but I wanted to outline what investigations and referrals we may need to consider in primary care if we encounter an unexplained high platelet count.

There are a couple of quality-improvement activities for us all to consider in primary care. Consider as a team how we would respond to an incidental finding of thrombocytosis on a full blood count. Also consider what are our safety-netting options for those found to have raised platelet counts but no other symptoms or risk factors for underlying malignancy.

Finally, I’ve produced a Medscape UK primary care hack or clinical aide-memoire on managing unexplained thrombocytosis and associated cancer risk in primary care for all healthcare professionals working in primary care. This can be found online. I hope you find this resource helpful.

Dr. Kevin Fernando, General practitioner partner with specialist interests in cardiovascular, renal, and metabolic medicine, North Berwick Group Practice in Scotland, has disclosed relevant financial relationships with Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Lilly, Menarini, Novartis, Novo Nordisk, Roche Diagnostics, Embecta, Roche Diabetes Care, Sanofi Menarini, and Daiichi Sankyo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

In this podcast, I’m going to talk about unexplained high platelet counts, or thrombocytosis, and the risk for cancer in primary care. Let’s start with a typical case we all might see in primary care.

Louisa is 47 years old and is the chief financial officer for a tech startup company. She presents to us in primary care feeling tired all the time — a very common presentation in primary care — with associated reduced appetite. Past medical history includes irritable bowel syndrome, and she’s an ex-smoker.

Systemic inquiry is unremarkable. Specifically, there is no history of weight loss. Louisa has not been prescribed any medication and uses over-the-counter remedies for her irritable bowel syndrome. Examination is also unremarkable. Blood tests were checked, which were all reassuring, except for a platelet count of 612 × 10⁹ cells/L (usual normal range, about 150-450).

What do we do next? Do we refer for an urgent chest x-ray to exclude lung cancer? Do we check a quantitative immunohistochemical fecal occult blood test (qFIT) to identify any occult bleeding in her stool? Do we refer for a routine upper gastrointestinal endoscopy or pelvic ultrasound scan to exclude any upper gastrointestinal or endometrial malignancy?

Do we simply repeat the bloods? If so, do we repeat them routinely or urgently, and indeed, which ones should we recheck?

Louisa has an unexplained thrombocytosis. How do we manage this in primary care? Thrombocytosis is generally defined as a raised platelet count over 450. Importantly, thrombocytosis is a common incidental finding in around 2% of those over 40 years of age attending primary care. Reassuringly, 80%-90% of thrombocytosis is reactive, secondary to acute blood loss, infection, or inflammation, and the majority of cases resolve within 3 months.

Why the concern with Louisa then? Although most cases are reactive, clinical guidance (for example, NICE suspected cancer guidance in the UK and Scottish suspected cancer guidance in Scotland) reminds us that unexplained thrombocytosis is a risk marker for some solid-tumor malignancies.

Previous studies have demonstrated that unexplained thrombocytosis is associated with a 1-year cancer incidence of 11.6% in males and 6.2% in females, well exceeding the standard 3% threshold warranting investigation for underlying malignancy. However, thrombocytosis should not be used as a stand-alone diagnostic or screening test for cancer, or indeed to rule out cancer.

Instead, unexplained thrombocytosis should prompt us to think cancer. The Scottish suspected cancer referral guidelines include thrombocytosis in the investigation criteria for what they call the LEGO-C cancers — L for lung, E for endometrial, G for gastric, O for oesophageal, and C for colorectal, which is a useful reminder for us all.

What further history, examination, and investigations might we consider in primary care if we identify an unexplained high platelet count? As always, we should use our clinical judgment and trust our clinical acumen.

We should consider all the possible underlying causes, including infection, inflammation, and blood loss, including menstrual blood loss in women; myeloproliferative disorders such as polycythemia rubra vera, chronic myeloid leukemia, and essential thrombocythemia; and, of course, underlying malignancy. If a likely underlying reversible cause is present (for example, a recent lower respiratory tract infection), simply repeating the full blood count in 4-6 weeks is quite appropriate to see if the thrombocytosis has resolved.

Remember, 80%-90% of cases are reactive thrombocytosis, and most cases resolve within 3 months. If thrombocytosis is unexplained or not resolving, consider checking ferritin levels to exclude iron deficiency. Consider checking C-reactive protein (CRP) levels to exclude any inflammation, and also consider checking a blood film to exclude any hematologic disorders, in addition, of course, to more detailed history-taking and examination to elicit any red flags.

We can also consider a JAK2 gene mutation test, if it is available to you locally, or a hematology referral if we suspect a myeloproliferative disorder. JAK2 is a genetic mutation that may be present in people with essential thrombocythemia and can indicate a diagnosis of polycythemia rubra vera.

Subsequent to this, and again using our clinical judgment, we then need to exclude the LEGO-C cancers. Consider urgent chest x-ray to exclude lung cancer or pelvic ultrasound in women to exclude endometrial cancer. Also, we should consider an upper gastrointestinal endoscopy, particularly in those individuals who have associated upper gastrointestinal symptoms and/or weight loss.

Finally, consider a qFIT to identify any occult bleeding in the stool, again if it’s available to you, or certainly if not, urgent lower gastrointestinal investigations to exclude colorectal cancer.

Alongside these possible investigations, as always, we should safety-net appropriately within agreed timeframes and check for resolution of the thrombocytosis according to the condition being suspected. Remember, most cases resolve within 3 months.

Returning to Louisa, what did I do? After seeing a platelet count of 600, I subsequently telephoned her and reexplored her history, which yielded nil else of note. Specifically, there was no history of unexplained weight loss, no history of upper or lower gastrointestinal symptoms, and certainly nothing significantly different from her usual irritable bowel syndrome symptoms. There were also no respiratory or genitourinary symptoms of note.

I did arrange for Louisa to undergo a chest x-ray over the next few days, though, as she was an ex-smoker. This was subsequently reported as normal. I appreciate chest x-rays have poor sensitivity for detecting lung cancer, as highlighted in a number of recent papers, but it was mutually agreed with Louisa that we would simply repeat her blood test in around 6 weeks. As well as repeating the full blood count, I arranged to check her ferritin, CRP, and a blood film, and then I was planning to reassess her clinically in person.

These bloods and my subsequent clinical review were reassuring. In fact, her platelet count had normalized after that 6 weeks had elapsed. Her thrombocytosis had resolved.

I didn’t arrange any further follow-up for her, but I did give her the usual safety netting advice to re-present to me or one of my colleagues if she does develop any worrying symptoms or signs.

I appreciate these scenarios are not always this straightforward, but I wanted to outline what investigations and referrals we may need to consider in primary care if we encounter an unexplained high platelet count.

There are a couple of quality-improvement activities for us all to consider in primary care. Consider as a team how we would respond to an incidental finding of thrombocytosis on a full blood count. Also consider what are our safety-netting options for those found to have raised platelet counts but no other symptoms or risk factors for underlying malignancy.

Finally, I’ve produced a Medscape UK primary care hack or clinical aide-memoire on managing unexplained thrombocytosis and associated cancer risk in primary care for all healthcare professionals working in primary care. This can be found online. I hope you find this resource helpful.

Dr. Kevin Fernando, General practitioner partner with specialist interests in cardiovascular, renal, and metabolic medicine, North Berwick Group Practice in Scotland, has disclosed relevant financial relationships with Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Lilly, Menarini, Novartis, Novo Nordisk, Roche Diagnostics, Embecta, Roche Diabetes Care, Sanofi Menarini, and Daiichi Sankyo.

A version of this article first appeared on Medscape.com.

The 340B Drug Pricing Program began as a noble endeavor, a lifeline designed to help safety-net providers deliver affordable care to America’s most vulnerable populations. However, over the years, this well-intentioned program has strayed from its original purpose, becoming a lucrative space where profits often outweigh patients. Loopholes, lax oversight, and unchecked expansion have allowed some powerful players, such as certain disproportionate share hospitals and their “child sites” as well as for-profit pharmacies, to exploit the system. What was once a program to uplift underserved communities now risks becoming a case study in how good intentions can go astray without accountability.

What exactly is this “340B program” that has captured headlines and the interest of legislatures around the country? What ensures that pharmaceutical manufacturers continue to participate in this program? How lucrative is it? How have underserved populations benefited and how is that measured? 
 

The 340B Drug Pricing Program was established in 1992 under the Public Health Service Act. Its primary goal is to enable covered entities (such as hospitals and clinics serving low-income and uninsured patients) to purchase outpatient drugs from pharmaceutical manufacturers at significantly reduced prices in order to support their care of the low-income and underserved populations. Drug makers are required to participate in this program as a condition of their participation in Medicaid and Medicare Part B and offer these steep discounts to covered entities if they want their medications to be available to 38% of patients nationwide. 

The hospitals that make up 78% of the program’s spending are known as disproportionate share hospitals (DSHs). These hospitals must be nonprofit and have at least an 11.75% “disproportionate” share of low-income Medicare or Medicaid inpatients. The other types of non-hospital entities qualifying for 340B pricing are known as initial “federal grantees.” Some examples include federally qualified health centers (FQHC), Ryan White HIV/AIDS program grantees, and other types of specialized clinics, such as hemophilia treatment centers. It needs to be noted up front that it is not these initial non-hospital federal grantees that need more oversight or reform, since according to the Health Resources and Services Administration (HRSA) 2023 report they make up only 22% of all program spending. It is the large, predominantly DSH health systems that are profiting immensely through exponential growth of their clinics and contract pharmacies. However, these health systems have not been able to show exactly who are their eligible patients and how they have been benefiting them.

When the 340B program was established to offer financial relief to hospitals and clinics taking care of the uninsured, it allowed them to save 20%-50% on drug purchases, which could be reinvested in patient care services. It was hoped that savings from the program could be used to provide free or low-cost medications, free vaccines, and other essential health services, essentially allowing safety-net providers to serve their communities despite financial constraints. The initial grantees are fulfilling that mission, but there are concerns regarding DSHs. (See the Coalition of State Rheumatology Organization’s 340B explanatory statement and policy position for more.)

 

Why Should Independent Practice Physicians Care About This?

Independent doctors should care about the lack of oversight in the 340B program because it affects healthcare costs, patient assistance, market competition, and access to affordable care for underserved and uninsured patients.

It also plays a strong hand in the healthcare consolidation that continues to threaten private physician practices. These acquisitions threaten the viability of independent practices in a variety of specialties across the United States, including rheumatology. HRSA allows 340B-covered entities to register their off-campus outpatient facilities, or child sites, under their 340B designation. Covered entities can acquire drugs at the 340B price, while imposing markups on the reimbursement they submit to private insurance. The additional revenue these covered entities can pocket provides them with a cash flow advantage that physician practices and outpatient clinics will never be able to actualize. This uneven playing field may make rheumatology practices more susceptible to hospital acquisitions. In fact, between 2016 and 2022, large 340B hospitals were responsible for approximately 80% of hospital acquisitions.

Perhaps the most important reason that we should all be concerned about the trajectory of this well-meaning program is that we have seen patients with hospital debt being sued by DSHs who receive 340B discounts so that they can take care of the low-income patients they are suing. We have seen Medicaid patients be turned away from a DSH clinic after being discharged from that hospital, because the hospital had reached its disproportionate share (11.75%) of inpatient Medicare and Medicaid patients. While not illegal, that type of behavior by covered entities is WRONG! Oversight and reform are needed if the 340B program is going to live up to its purpose and not be just another well-intentioned program not fulfilling its mission.

 

Areas of Concern

There has been controversy regarding the limited oversight of the 340B program by HRSA, leading to abuse of the program. There are deep concerns regarding a lack of transparency in how savings from the program are being used, and there are concerns about the challenges associated with accurate tracking and reporting of 340B discounts, possibly leading to the duplication of discounts for both Medicaid and 340B. For example, a “duplicate discount” occurs if a manufacturer sells medications to a DSH at the 340B price and later pays a Medicaid rebate on the same drug. The extent of duplicate discounts in the 340B program is unknown. However, an audit of 1,536 cases conducted by HRSA between 2012 and 2019 found 429 instances of noncompliance related to duplicate discounts, which is nearly 30% of cases.

DSHs and their contracted pharmacies have been accused of exploiting the program by increasing the number of contract pharmacies and expanding the number of offsite outpatient clinics to maximize profits. As of mid-2024, the number of 340B contract pharmacies, counted by Drug Channels Institute (DCI), numbered 32,883 unique locations. According to DCI, the top five pharmacies in the program happen also to be among the top pharmacy revenue generators and are “for-profit.” They are CVS, Walgreens, Walmart, Express Scripts, and Optum RX. Additionally, a study in JAMA Health Forum showed that, from 2011 to 2019, contract pharmacies in areas with the lowest income decreased by 5.6% while those in the most affluent neighborhoods grew by 5%. 

There also has been tremendous growth in the number of covered entities in the 340B program, which grew from just over 8,100 in 2000 to 50,000 in 2020. Before 2004, DSHs made up less than 10% of these entities, but by 2020, they accounted for over 60%. Another study shows that DSHs are expanding their offsite outpatient clinics (“child clinics”) into the affluent neighborhoods serving commercially insured patients who are not low income, to capture the high commercial reimbursements for medications they acquired at steeply discounted prices. This clearly is diverting care away from the intended beneficiaries of the 340B program. 

Furthermore, DSHs have been acquiring specialty practices that prescribe some of the most expensive drugs, in order to take advantage of commercial reimbursement for medications that were acquired at the 340B discount price. Independent oncology practices have complained specifically about this happening in their area, where in some cases the DSHs have “stolen” their patients to profit off of the 340B pricing margins. This has the unintended consequence of increasing government spending, according to a study in the New England Journal of Medicine that showed price markups at 340B eligible hospitals were 6.59 times as high as those in independent physician practices after accounting for drug, patient, and geographic factors.

 

Legal Challenges and Legislation

On May 21, 2024, the US Court of Appeals for the DC Circuit issued a unanimous decision in favor of drug manufacturers, finding that certain manufacturer restrictions on the use of contract pharmacies under the 340B drug pricing program are permissible. The court’s decision follows a lower court (3rd Circuit) ruling which concluded that the 340B statute does not require manufacturers to deliver 340B drugs to an “unlimited number of contract pharmacies.” We’re still awaiting a decision from the 7th Circuit Court on a similar issue. If the 7th Circuit agrees with the government, creating a split decision, there is an increase in the likelihood that the Supreme Court would take up the case.

Johnson & Johnson has also sued the federal government for blocking their proposed use of a rebate model for DSHs that purchase through 340B two of its medications, Stelara and Xarelto, whose maximum fair price was negotiated through the Inflation Reduction Act’s Medicare Drug Price Negotiation Program. J&J states this would ensure that the claims are actually acquired and dispensed by a covered 340B entity, as well as ensuring there are no duplicate discounts as statutorily required by the IRA. When initially proposed, HRSA threatened to remove J&J’s access to Medicare and Medicaid if it pursued this change. J&J’s suit challenges that decision.

However, seven states (Arkansas, Kansas, Louisiana, Minnesota, Missouri, Mississippi, and West Virginia) have been active on this issue, passing laws to prevent manufacturers from limiting contract pharmacies’ ability to acquire 340B-discounted drugs. The model legislation also bans restrictions on the “number, location, ownership, or type of 340B contract pharmacy.”

It should also be noted that there are states that are looking for ways to encourage certain independent private practice specialties (such as gastroenterology and rheumatology) to see Medicaid patients, as well as increase testing for sexually transmitted diseases, by offering the possibility of obtaining 340B pricing in their clinics. 

Shifting our focus to Congress, six bipartisan Senators, known as the Group of 6, are working to modernize the 340B program, which hasn’t been updated since the original law in 1992. In 2024, legislation was introduced (see here and here) to reform a number of the features of the 340B drug discount program, including transparency, contract pharmacy requirements, and federal agency oversight.

 

Who’s Guarding the Hen House?

The Government Accountability Office and the Office of Inspector General over the last 5-10 years have asked HRSA to better define an “eligible” patient, to have more specifics concerning hospital eligibility criteria, and to have better oversight of the program to avoid duplicate discounts. HRSA has said that it doesn’t have the ability or the funding to achieve some of these goals. Consequently, little has been done on any of these fronts, creating frustration among pharmaceutical manufacturers and those calling for more oversight of the program to ensure that eligible patients are receiving the benefit of 340B pricing. Again, these frustrations are not pointed at the initial federally qualified centers or “grantees.”

HRSA now audits 200 covered entities a year, which is less than 2% of entities participating in the 340B program. HRSA expects the 340B entities themselves to have an oversight committee in place to ensure compliance with program requirements. 

So essentially, the fox is guarding the hen house?

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of advocacy and government affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

The 340B Drug Pricing Program began as a noble endeavor, a lifeline designed to help safety-net providers deliver affordable care to America’s most vulnerable populations. However, over the years, this well-intentioned program has strayed from its original purpose, becoming a lucrative space where profits often outweigh patients. Loopholes, lax oversight, and unchecked expansion have allowed some powerful players, such as certain disproportionate share hospitals and their “child sites” as well as for-profit pharmacies, to exploit the system. What was once a program to uplift underserved communities now risks becoming a case study in how good intentions can go astray without accountability.

What exactly is this “340B program” that has captured headlines and the interest of legislatures around the country? What ensures that pharmaceutical manufacturers continue to participate in this program? How lucrative is it? How have underserved populations benefited and how is that measured? 
 

The 340B Drug Pricing Program was established in 1992 under the Public Health Service Act. Its primary goal is to enable covered entities (such as hospitals and clinics serving low-income and uninsured patients) to purchase outpatient drugs from pharmaceutical manufacturers at significantly reduced prices in order to support their care of the low-income and underserved populations. Drug makers are required to participate in this program as a condition of their participation in Medicaid and Medicare Part B and offer these steep discounts to covered entities if they want their medications to be available to 38% of patients nationwide. 

The hospitals that make up 78% of the program’s spending are known as disproportionate share hospitals (DSHs). These hospitals must be nonprofit and have at least an 11.75% “disproportionate” share of low-income Medicare or Medicaid inpatients. The other types of non-hospital entities qualifying for 340B pricing are known as initial “federal grantees.” Some examples include federally qualified health centers (FQHC), Ryan White HIV/AIDS program grantees, and other types of specialized clinics, such as hemophilia treatment centers. It needs to be noted up front that it is not these initial non-hospital federal grantees that need more oversight or reform, since according to the Health Resources and Services Administration (HRSA) 2023 report they make up only 22% of all program spending. It is the large, predominantly DSH health systems that are profiting immensely through exponential growth of their clinics and contract pharmacies. However, these health systems have not been able to show exactly who are their eligible patients and how they have been benefiting them.

When the 340B program was established to offer financial relief to hospitals and clinics taking care of the uninsured, it allowed them to save 20%-50% on drug purchases, which could be reinvested in patient care services. It was hoped that savings from the program could be used to provide free or low-cost medications, free vaccines, and other essential health services, essentially allowing safety-net providers to serve their communities despite financial constraints. The initial grantees are fulfilling that mission, but there are concerns regarding DSHs. (See the Coalition of State Rheumatology Organization’s 340B explanatory statement and policy position for more.)

 

Why Should Independent Practice Physicians Care About This?

Independent doctors should care about the lack of oversight in the 340B program because it affects healthcare costs, patient assistance, market competition, and access to affordable care for underserved and uninsured patients.

It also plays a strong hand in the healthcare consolidation that continues to threaten private physician practices. These acquisitions threaten the viability of independent practices in a variety of specialties across the United States, including rheumatology. HRSA allows 340B-covered entities to register their off-campus outpatient facilities, or child sites, under their 340B designation. Covered entities can acquire drugs at the 340B price, while imposing markups on the reimbursement they submit to private insurance. The additional revenue these covered entities can pocket provides them with a cash flow advantage that physician practices and outpatient clinics will never be able to actualize. This uneven playing field may make rheumatology practices more susceptible to hospital acquisitions. In fact, between 2016 and 2022, large 340B hospitals were responsible for approximately 80% of hospital acquisitions.

Perhaps the most important reason that we should all be concerned about the trajectory of this well-meaning program is that we have seen patients with hospital debt being sued by DSHs who receive 340B discounts so that they can take care of the low-income patients they are suing. We have seen Medicaid patients be turned away from a DSH clinic after being discharged from that hospital, because the hospital had reached its disproportionate share (11.75%) of inpatient Medicare and Medicaid patients. While not illegal, that type of behavior by covered entities is WRONG! Oversight and reform are needed if the 340B program is going to live up to its purpose and not be just another well-intentioned program not fulfilling its mission.

 

Areas of Concern

There has been controversy regarding the limited oversight of the 340B program by HRSA, leading to abuse of the program. There are deep concerns regarding a lack of transparency in how savings from the program are being used, and there are concerns about the challenges associated with accurate tracking and reporting of 340B discounts, possibly leading to the duplication of discounts for both Medicaid and 340B. For example, a “duplicate discount” occurs if a manufacturer sells medications to a DSH at the 340B price and later pays a Medicaid rebate on the same drug. The extent of duplicate discounts in the 340B program is unknown. However, an audit of 1,536 cases conducted by HRSA between 2012 and 2019 found 429 instances of noncompliance related to duplicate discounts, which is nearly 30% of cases.

DSHs and their contracted pharmacies have been accused of exploiting the program by increasing the number of contract pharmacies and expanding the number of offsite outpatient clinics to maximize profits. As of mid-2024, the number of 340B contract pharmacies, counted by Drug Channels Institute (DCI), numbered 32,883 unique locations. According to DCI, the top five pharmacies in the program happen also to be among the top pharmacy revenue generators and are “for-profit.” They are CVS, Walgreens, Walmart, Express Scripts, and Optum RX. Additionally, a study in JAMA Health Forum showed that, from 2011 to 2019, contract pharmacies in areas with the lowest income decreased by 5.6% while those in the most affluent neighborhoods grew by 5%. 

There also has been tremendous growth in the number of covered entities in the 340B program, which grew from just over 8,100 in 2000 to 50,000 in 2020. Before 2004, DSHs made up less than 10% of these entities, but by 2020, they accounted for over 60%. Another study shows that DSHs are expanding their offsite outpatient clinics (“child clinics”) into the affluent neighborhoods serving commercially insured patients who are not low income, to capture the high commercial reimbursements for medications they acquired at steeply discounted prices. This clearly is diverting care away from the intended beneficiaries of the 340B program. 

Furthermore, DSHs have been acquiring specialty practices that prescribe some of the most expensive drugs, in order to take advantage of commercial reimbursement for medications that were acquired at the 340B discount price. Independent oncology practices have complained specifically about this happening in their area, where in some cases the DSHs have “stolen” their patients to profit off of the 340B pricing margins. This has the unintended consequence of increasing government spending, according to a study in the New England Journal of Medicine that showed price markups at 340B eligible hospitals were 6.59 times as high as those in independent physician practices after accounting for drug, patient, and geographic factors.

 

Legal Challenges and Legislation

On May 21, 2024, the US Court of Appeals for the DC Circuit issued a unanimous decision in favor of drug manufacturers, finding that certain manufacturer restrictions on the use of contract pharmacies under the 340B drug pricing program are permissible. The court’s decision follows a lower court (3rd Circuit) ruling which concluded that the 340B statute does not require manufacturers to deliver 340B drugs to an “unlimited number of contract pharmacies.” We’re still awaiting a decision from the 7th Circuit Court on a similar issue. If the 7th Circuit agrees with the government, creating a split decision, there is an increase in the likelihood that the Supreme Court would take up the case.

Johnson & Johnson has also sued the federal government for blocking their proposed use of a rebate model for DSHs that purchase through 340B two of its medications, Stelara and Xarelto, whose maximum fair price was negotiated through the Inflation Reduction Act’s Medicare Drug Price Negotiation Program. J&J states this would ensure that the claims are actually acquired and dispensed by a covered 340B entity, as well as ensuring there are no duplicate discounts as statutorily required by the IRA. When initially proposed, HRSA threatened to remove J&J’s access to Medicare and Medicaid if it pursued this change. J&J’s suit challenges that decision.

However, seven states (Arkansas, Kansas, Louisiana, Minnesota, Missouri, Mississippi, and West Virginia) have been active on this issue, passing laws to prevent manufacturers from limiting contract pharmacies’ ability to acquire 340B-discounted drugs. The model legislation also bans restrictions on the “number, location, ownership, or type of 340B contract pharmacy.”

It should also be noted that there are states that are looking for ways to encourage certain independent private practice specialties (such as gastroenterology and rheumatology) to see Medicaid patients, as well as increase testing for sexually transmitted diseases, by offering the possibility of obtaining 340B pricing in their clinics. 

Shifting our focus to Congress, six bipartisan Senators, known as the Group of 6, are working to modernize the 340B program, which hasn’t been updated since the original law in 1992. In 2024, legislation was introduced (see here and here) to reform a number of the features of the 340B drug discount program, including transparency, contract pharmacy requirements, and federal agency oversight.

 

Who’s Guarding the Hen House?

The Government Accountability Office and the Office of Inspector General over the last 5-10 years have asked HRSA to better define an “eligible” patient, to have more specifics concerning hospital eligibility criteria, and to have better oversight of the program to avoid duplicate discounts. HRSA has said that it doesn’t have the ability or the funding to achieve some of these goals. Consequently, little has been done on any of these fronts, creating frustration among pharmaceutical manufacturers and those calling for more oversight of the program to ensure that eligible patients are receiving the benefit of 340B pricing. Again, these frustrations are not pointed at the initial federally qualified centers or “grantees.”

HRSA now audits 200 covered entities a year, which is less than 2% of entities participating in the 340B program. HRSA expects the 340B entities themselves to have an oversight committee in place to ensure compliance with program requirements. 

So essentially, the fox is guarding the hen house?

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of advocacy and government affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

The 340B Drug Pricing Program began as a noble endeavor, a lifeline designed to help safety-net providers deliver affordable care to America’s most vulnerable populations. However, over the years, this well-intentioned program has strayed from its original purpose, becoming a lucrative space where profits often outweigh patients. Loopholes, lax oversight, and unchecked expansion have allowed some powerful players, such as certain disproportionate share hospitals and their “child sites” as well as for-profit pharmacies, to exploit the system. What was once a program to uplift underserved communities now risks becoming a case study in how good intentions can go astray without accountability.

What exactly is this “340B program” that has captured headlines and the interest of legislatures around the country? What ensures that pharmaceutical manufacturers continue to participate in this program? How lucrative is it? How have underserved populations benefited and how is that measured? 
 

The 340B Drug Pricing Program was established in 1992 under the Public Health Service Act. Its primary goal is to enable covered entities (such as hospitals and clinics serving low-income and uninsured patients) to purchase outpatient drugs from pharmaceutical manufacturers at significantly reduced prices in order to support their care of the low-income and underserved populations. Drug makers are required to participate in this program as a condition of their participation in Medicaid and Medicare Part B and offer these steep discounts to covered entities if they want their medications to be available to 38% of patients nationwide. 

The hospitals that make up 78% of the program’s spending are known as disproportionate share hospitals (DSHs). These hospitals must be nonprofit and have at least an 11.75% “disproportionate” share of low-income Medicare or Medicaid inpatients. The other types of non-hospital entities qualifying for 340B pricing are known as initial “federal grantees.” Some examples include federally qualified health centers (FQHC), Ryan White HIV/AIDS program grantees, and other types of specialized clinics, such as hemophilia treatment centers. It needs to be noted up front that it is not these initial non-hospital federal grantees that need more oversight or reform, since according to the Health Resources and Services Administration (HRSA) 2023 report they make up only 22% of all program spending. It is the large, predominantly DSH health systems that are profiting immensely through exponential growth of their clinics and contract pharmacies. However, these health systems have not been able to show exactly who are their eligible patients and how they have been benefiting them.

When the 340B program was established to offer financial relief to hospitals and clinics taking care of the uninsured, it allowed them to save 20%-50% on drug purchases, which could be reinvested in patient care services. It was hoped that savings from the program could be used to provide free or low-cost medications, free vaccines, and other essential health services, essentially allowing safety-net providers to serve their communities despite financial constraints. The initial grantees are fulfilling that mission, but there are concerns regarding DSHs. (See the Coalition of State Rheumatology Organization’s 340B explanatory statement and policy position for more.)

 

Why Should Independent Practice Physicians Care About This?

Independent doctors should care about the lack of oversight in the 340B program because it affects healthcare costs, patient assistance, market competition, and access to affordable care for underserved and uninsured patients.

It also plays a strong hand in the healthcare consolidation that continues to threaten private physician practices. These acquisitions threaten the viability of independent practices in a variety of specialties across the United States, including rheumatology. HRSA allows 340B-covered entities to register their off-campus outpatient facilities, or child sites, under their 340B designation. Covered entities can acquire drugs at the 340B price, while imposing markups on the reimbursement they submit to private insurance. The additional revenue these covered entities can pocket provides them with a cash flow advantage that physician practices and outpatient clinics will never be able to actualize. This uneven playing field may make rheumatology practices more susceptible to hospital acquisitions. In fact, between 2016 and 2022, large 340B hospitals were responsible for approximately 80% of hospital acquisitions.

Perhaps the most important reason that we should all be concerned about the trajectory of this well-meaning program is that we have seen patients with hospital debt being sued by DSHs who receive 340B discounts so that they can take care of the low-income patients they are suing. We have seen Medicaid patients be turned away from a DSH clinic after being discharged from that hospital, because the hospital had reached its disproportionate share (11.75%) of inpatient Medicare and Medicaid patients. While not illegal, that type of behavior by covered entities is WRONG! Oversight and reform are needed if the 340B program is going to live up to its purpose and not be just another well-intentioned program not fulfilling its mission.

 

Areas of Concern

There has been controversy regarding the limited oversight of the 340B program by HRSA, leading to abuse of the program. There are deep concerns regarding a lack of transparency in how savings from the program are being used, and there are concerns about the challenges associated with accurate tracking and reporting of 340B discounts, possibly leading to the duplication of discounts for both Medicaid and 340B. For example, a “duplicate discount” occurs if a manufacturer sells medications to a DSH at the 340B price and later pays a Medicaid rebate on the same drug. The extent of duplicate discounts in the 340B program is unknown. However, an audit of 1,536 cases conducted by HRSA between 2012 and 2019 found 429 instances of noncompliance related to duplicate discounts, which is nearly 30% of cases.

DSHs and their contracted pharmacies have been accused of exploiting the program by increasing the number of contract pharmacies and expanding the number of offsite outpatient clinics to maximize profits. As of mid-2024, the number of 340B contract pharmacies, counted by Drug Channels Institute (DCI), numbered 32,883 unique locations. According to DCI, the top five pharmacies in the program happen also to be among the top pharmacy revenue generators and are “for-profit.” They are CVS, Walgreens, Walmart, Express Scripts, and Optum RX. Additionally, a study in JAMA Health Forum showed that, from 2011 to 2019, contract pharmacies in areas with the lowest income decreased by 5.6% while those in the most affluent neighborhoods grew by 5%. 

There also has been tremendous growth in the number of covered entities in the 340B program, which grew from just over 8,100 in 2000 to 50,000 in 2020. Before 2004, DSHs made up less than 10% of these entities, but by 2020, they accounted for over 60%. Another study shows that DSHs are expanding their offsite outpatient clinics (“child clinics”) into the affluent neighborhoods serving commercially insured patients who are not low income, to capture the high commercial reimbursements for medications they acquired at steeply discounted prices. This clearly is diverting care away from the intended beneficiaries of the 340B program. 

Furthermore, DSHs have been acquiring specialty practices that prescribe some of the most expensive drugs, in order to take advantage of commercial reimbursement for medications that were acquired at the 340B discount price. Independent oncology practices have complained specifically about this happening in their area, where in some cases the DSHs have “stolen” their patients to profit off of the 340B pricing margins. This has the unintended consequence of increasing government spending, according to a study in the New England Journal of Medicine that showed price markups at 340B eligible hospitals were 6.59 times as high as those in independent physician practices after accounting for drug, patient, and geographic factors.

 

Legal Challenges and Legislation

On May 21, 2024, the US Court of Appeals for the DC Circuit issued a unanimous decision in favor of drug manufacturers, finding that certain manufacturer restrictions on the use of contract pharmacies under the 340B drug pricing program are permissible. The court’s decision follows a lower court (3rd Circuit) ruling which concluded that the 340B statute does not require manufacturers to deliver 340B drugs to an “unlimited number of contract pharmacies.” We’re still awaiting a decision from the 7th Circuit Court on a similar issue. If the 7th Circuit agrees with the government, creating a split decision, there is an increase in the likelihood that the Supreme Court would take up the case.

Johnson & Johnson has also sued the federal government for blocking their proposed use of a rebate model for DSHs that purchase through 340B two of its medications, Stelara and Xarelto, whose maximum fair price was negotiated through the Inflation Reduction Act’s Medicare Drug Price Negotiation Program. J&J states this would ensure that the claims are actually acquired and dispensed by a covered 340B entity, as well as ensuring there are no duplicate discounts as statutorily required by the IRA. When initially proposed, HRSA threatened to remove J&J’s access to Medicare and Medicaid if it pursued this change. J&J’s suit challenges that decision.

However, seven states (Arkansas, Kansas, Louisiana, Minnesota, Missouri, Mississippi, and West Virginia) have been active on this issue, passing laws to prevent manufacturers from limiting contract pharmacies’ ability to acquire 340B-discounted drugs. The model legislation also bans restrictions on the “number, location, ownership, or type of 340B contract pharmacy.”

It should also be noted that there are states that are looking for ways to encourage certain independent private practice specialties (such as gastroenterology and rheumatology) to see Medicaid patients, as well as increase testing for sexually transmitted diseases, by offering the possibility of obtaining 340B pricing in their clinics. 

Shifting our focus to Congress, six bipartisan Senators, known as the Group of 6, are working to modernize the 340B program, which hasn’t been updated since the original law in 1992. In 2024, legislation was introduced (see here and here) to reform a number of the features of the 340B drug discount program, including transparency, contract pharmacy requirements, and federal agency oversight.

 

Who’s Guarding the Hen House?

The Government Accountability Office and the Office of Inspector General over the last 5-10 years have asked HRSA to better define an “eligible” patient, to have more specifics concerning hospital eligibility criteria, and to have better oversight of the program to avoid duplicate discounts. HRSA has said that it doesn’t have the ability or the funding to achieve some of these goals. Consequently, little has been done on any of these fronts, creating frustration among pharmaceutical manufacturers and those calling for more oversight of the program to ensure that eligible patients are receiving the benefit of 340B pricing. Again, these frustrations are not pointed at the initial federally qualified centers or “grantees.”

HRSA now audits 200 covered entities a year, which is less than 2% of entities participating in the 340B program. HRSA expects the 340B entities themselves to have an oversight committee in place to ensure compliance with program requirements. 

So essentially, the fox is guarding the hen house?

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is the CSRO’s vice president of advocacy and government affairs and its immediate past president, as well as past chair of the Alliance for Safe Biologic Medicines and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania. 

In this series, I’ll be giving you my top studies presented at ACG 2024, which will be split into two parts. These studies are not presented in any order of priority because I think they all have clinical applications, some of which are more immediate. Where possible, I’ll also provide you with some teaching points that occurred to me when I viewed the data in these presentations. 

 

Repetitive Use Injuries Among Endoscopists 

First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward. 

This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.

Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work. 

Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response. 

Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.

There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day. 

Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength. 

The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this. 

Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.

During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from. 

So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward. 

 

On-Demand Vonoprazan for Heartburn 

The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.

The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand. 

This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.

Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour. 

We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.

 

Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence

The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy. 

Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients. 

This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.

There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12. 

Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19. 

The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone. 

 

Apraglutide’s Efficacy in Short-Bowel Syndrome 

The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.

Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics. 

Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.

Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint. 

Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily. 

From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026. 

This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.

 

Biologics for Treating Immune Checkpoint Inhibitor Colitis

The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients. 

The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well. 

ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.

Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.

The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups. 

There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.

There are two additional teaching points I’d like to convey.

First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.

Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well. 

These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.

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 appeared on Medscape.com.

I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania. 

In this series, I’ll be giving you my top studies presented at ACG 2024, which will be split into two parts. These studies are not presented in any order of priority because I think they all have clinical applications, some of which are more immediate. Where possible, I’ll also provide you with some teaching points that occurred to me when I viewed the data in these presentations. 

 

Repetitive Use Injuries Among Endoscopists 

First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward. 

This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.

Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work. 

Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response. 

Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.

There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day. 

Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength. 

The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this. 

Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.

During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from. 

So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward. 

 

On-Demand Vonoprazan for Heartburn 

The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.

The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand. 

This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.

Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour. 

We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.

 

Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence

The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy. 

Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients. 

This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.

There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12. 

Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19. 

The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone. 

 

Apraglutide’s Efficacy in Short-Bowel Syndrome 

The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.

Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics. 

Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.

Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint. 

Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily. 

From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026. 

This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.

 

Biologics for Treating Immune Checkpoint Inhibitor Colitis

The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients. 

The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well. 

ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.

Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.

The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups. 

There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.

There are two additional teaching points I’d like to convey.

First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.

Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well. 

These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.

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 appeared on Medscape.com.

I’ve just returned from the annual meeting of the American College of Gastroenterology (ACG), which was held in Philadelphia, Pennsylvania. 

In this series, I’ll be giving you my top studies presented at ACG 2024, which will be split into two parts. These studies are not presented in any order of priority because I think they all have clinical applications, some of which are more immediate. Where possible, I’ll also provide you with some teaching points that occurred to me when I viewed the data in these presentations. 

 

Repetitive Use Injuries Among Endoscopists 

First is a study that assessed musculoskeletal injuries that occurred while performing endoscopy, which is a large part of what we do as gastroenterologists. I’ve personally experienced virtually all these injuries during my 45-plus years in the field. These findings provide a useful perspective of what we can do to potentially avoid such injuries going forward. 

This study comes to us from researchers at the University of Utah, who looked at an author-developed and validated questionnaire called QuickDash (Disability of Arm, Shoulder, Hand). Endoscopists were evaluated by occupational therapists in their department, who looked at strength testing as well as a series of provocative tests to identify injuries.

Thirty-five endoscopists were enrolled. Overall, 34% reported experiencing pain and 17% reported numbness. In the previous week, 48% had been bothered by pain and 11% by tingling, and 17% reported limitations on what they could do at work. 

Additionally, 17% experienced interrupted sleep. I think that finding is particularly important, because when you have fragmented sleep it lowers sensory thresholds. Essentially, this means that the day after interrupted sleep, you respond with a heightened sensory response. 

Physical testing showed reduction in grip strength in approximately half of participants, including both right and left grip. More than 70% had at least one abnormal positive provocative test.

There were a couple factors associated with an increased risk for adverse outcomes. Those who performed 20 or more procedures a week were at higher risk of pain (P = .007). I recognize that some of you probably perform 20 or more endoscopies in a single day. 

Negative outcomes were also more likely to occur among physicians performing biliary endoscopy. Performing endoscopic retrograde cholangiopancreatography during 20%-60% of the week resulted in greater likelihood of experiencing decreased bilateral pinch strength. 

The bottom line is that there’s an extremely high prevalence of repetitive use injury among endoscopists. Whether you’re just starting out, mid-career, or more senior, you need to be aware of this. 

Kudos to the ACG who put together hands-on sessions across 2 days with extended ergonomics training provided by physical therapists with expertise in this area. These sessions were standing room only every time I visited them.

During the meeting, the ACG also announced the publication of a new book, Ergonomics for Endoscopy: Optimal Preparation, Performance, and Recovery, that is available on the ACG’s website. I had the privilege to meet the two authors, survey the book, and briefly discuss it with them. It’s phenomenal, and something that I think every endoscopist can benefit from. 

So, in summary, don’t put aside these concerns. It’s your career, and the better we can do in preventing these injuries, I think the better you’ll feel going forward. 

 

On-Demand Vonoprazan for Heartburn 

The second study of note dealt with vonoprazan, a potassium-competitive acid blocker.

The question surrounding vonoprazan is whether it has clinical value as an on-demand option rather than simply as maintenance therapy administered via daily dosing. Previous results have suggested that it may have a more rapid effect when it’s taken on demand. 

This post hoc analysis of a randomized trial evaluated a 4-week run-in period during which patients received vonoprazan 20 mg daily, followed by a 6-week period after which patients switched to on-demand therapy. To be eligible, during the run-in period patients had to be 80% compliant with the study drug and report no heartburn during the last 7 days of treatment. If so, they were then randomized to receive vonoprazan at 10 mg, 20 mg, or 40 mg, or placebo.

Eligible patients reported 16% heartburn-free days during the screening period. During the run-in period, heartburn-free days increased to 83% among those taking vonoprazan 20 mg daily. When this was stopped and patients transitioned to on-demand vonoprazan, they still had a very high rate of heartburn-free days, ranging from 71% to 75%. Over 90% in the treatment group had their symptoms improved within 2 hours, with improvement noted as early as within 1 hour. 

We know that proton pump inhibitors don’t produce this effect, which presents a challenge for us. This study suggests there may be a very strong role for on-demand therapy in patients who have reflux, which certainly showed in terms of responsiveness during the 4-week run-in period.

 

Rifaximin Monotherapy Reduces Risk for Overt Hepatic Encephalopathy Recurrence

The next trial looked at rifaximin monotherapy for prevention of relapse of overt hepatic encephalopathy. 

Rifaximin has been added to the baseline primary treatment of lactulose, a combination that has been analyzed in pivotal studies. However, lactulose is a difficult drug to titrate. We typically ask patients to let us know if they have Bristol Stool Scale scores ≥ 6. This results in an inordinate number of calls back to the clinic or office. Diarrhea is a particular problem in these patients. 

This study, which was presented by Dr Jasmohan S. Bajaj from Virginia Commonwealth University, analyzed data from two randomized trials: a phase 3, double-blind trial and a phase 4 open-label trial. Both studies were conducted in patients with Child-Pugh classification A and B cirrhosis, whose overt hepatic encephalopathy was graded with a Conn score ≤ 1. Researchers only looked at those patients who received rifaximin 550 mg twice daily without lactulose, or lactulose titrated to a target of two to three soft stools a day plus placebo. The primary endpoint, which was used in both trials, was time to first breakthrough overt hepatic encephalopathy episode, measured as a Conn score ≥ 2.

There were 125 patients in the rifaximin group and 145 patients in the lactulose group. Patients in both groups had mean age of 57 years and a median Model for End-Stage Liver Disease score of 12. 

Treatment with rifaximin produced significantly striking results. In the rifaximin group, the risk for breakthrough overt hepatic encephalopathy episodes was reduced by 60%, with a number needed to treat of 4, which is extremely powerful. Regarding mortality reduction, the number needed to treat with rifaximin alone was 19. 

The take-away message here is that it’s difficult to use lactulose. We frequently have to stop it. These results provide reassurance that rifaximin has a dramatic effect even when used by itself. The recommended first-line therapy is still to begin with lactulose, but this study provides us with very strong data regarding the use of rifaximin alone. 

 

Apraglutide’s Efficacy in Short-Bowel Syndrome 

The fourth study I’d like to highlight adds to the growing data around a long-acting glucagon-like peptide 2 analog, apraglutide.

Results from the phase 3, double-blind STARS trial were first presented at Digestive Disease Week earlier in the year. They showed that apraglutide had efficacy and contributed to a reduction in the risk for needing parenteral support, maintenance of weight, and fluid requirements in patients with short-bowel syndrome and intestinal failure. However, questions remained regarding whether there were variations in response based on patient demographics and short-bowel syndrome–specific characteristics. 

Researchers looked at a subgroup of patients from the STARS trial. The primary endpoint remained the same as in the main trial: relative change from baseline in actual parenteral support weekly volume at week 24. However, rather than measure it in the overall population, they did so according to geographic region, gender, age, body weight, race and ethnicity, and short-bowel syndrome characteristics, including differences in parenteral support volume, length of the remnant small intestine, and time from short-bowel syndrome diagnosis.

Across all these demographic and disease characteristic categories, there was absolutely no difference in the primary endpoint. 

Apraglutide seems to be inordinately promising. This is a once-weekly treatment, as opposed to liraglutide, which is problematic because it has to be given daily. 

From what I understand, apraglutide has been offered a fast-track status by the US Food and Drug Administration. Again, from what I’ve heard, it will be evaluated upon submission beginning sometime in the first quarter of 2025, which may mean that apraglutide could be available as early as 2026. 

This would be a big deal for patients with short-bowel syndrome who would have a once-weekly treatment option as opposed to daily treatment and its accompanying problems of compliance and relatively reduced response.

 

Biologics for Treating Immune Checkpoint Inhibitor Colitis

The final study I want to discuss in this presentation dealt with adverse responses to immune checkpoint inhibitor (ICI) therapy. We see this increasingly in our clinics as ICIs become more widely used. They are wonderful drugs, but ICI-induced colitis can occur in up to 30% of patients. 

The oncologic approach is to try and stay the course, while gastroenterologists are tasked with treating the colitis so that these patients can maintain their cancer treatment. Steroid therapy is the primary first-line treatment against ICI colitis, but the use of biologic therapy with infliximab or vedolizumab has been associated with favorable outcomes as well. 

ICI colitis is graded on a scale. Whereas grade 1 ICI colitis indicates increased stool frequency of less than four a day and the absence of symptoms, grade 2 indicates a progression to a stool frequency of four to six times a day, the appearance of blood or mucus in the stool, and symptoms like abdominal pain.

Researchers sought to answer the question of which treatment is better for patients with moderate to severe ICI colitis: infliximab or vedolizumab? They performed a database analysis of patients at their institution who received at least one dose of these biologics. The endpoint was sustained clinical response (ie, without a recurrent colitis episode), as well as patients achieving improvement to grade 1 ICI colitis.

The data for infliximab and vedolizumab were quite good. Sustained clinical response was noted in 91% of patients receiving infliximab and 86% receiving vedolizumab. There was no difference in infection risk between the groups. 

There’s a teaching point in the study’s other key finding, which is that following biologic initiation, steroids were more rapidly discontinued with vedolizumab vs infliximab (median, 25 days vs 56 days, respectively). Therefore, vedolizumab may have the added benefit of patients being able to get off steroids more quickly. That’s the take-home message: Vedolizumab may be better. We certainly are comfortable with both biologics, but patients getting off steroids would be better.

There are two additional teaching points I’d like to convey.

First, don’t forget to perform a biopsy, because there are patients who may have cytomegalovirus colitis and we don’t want to miss it. A biopsy may also reveal whether they have a macroscopically normal rectosigmoid. So, you should biopsy to look for microscopic changes. As 98% of ICI colitis cases involve the left colon, you can get by with just using a flexible sigmoidoscopy.

Second, don’t forget to check for celiac disease. Patients taking ICIs may develop celiac disease as a side effect of treatment. So, I always order a celiac profile as well. 

These are, in my opinion, five of the top studies from ACG 2024, with the remaining studies to be discussed in my next video. They all provide opportunities to help us improve our patients’ health.

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 appeared on Medscape.com.

I’ve tried to retire from medicine. Really. Proofs of my sincerity include a true retirement from performing procedures and the closing of two office practices. I even attended the wonderful retirement party my daughters threw for me. 

I had great plans for my newfound leisure time. I purchased about a thousand colored pencils to map my family ancestry. I wore out many magic erasers in my cleaning efforts. I cajoled my husband, Tony, to help me build not one, but three, gardens in our yard. Upon realizing I had no more weeds or closets to conquer, I began a Dante-like descent into a dark abyss. I felt my sadness was justified. After all, I had immensely enjoyed my early medical life. 

 

From Private Practice to Being Employed

I had a joint cardiology practice with the great Jim Whiteside, MD, in South Central Kentucky for 24 years. Our schedule was always bursting at the seams in the heart of tobacco country. We opened the first cath lab in our hospital, inspired the purchase of a new nuclear scanner, and expanded the stress echo lab. After a 6-year odyssey, we successfully championed primary PCI without surgery on site (along with Ephraim McDowell Regional Medical Center in Danville, Kentucky). As our services expanded, we remodeled to accommodate three cardiologists and two nurse practitioners. Simultaneously, we lobbied our city council and mayor to pass smoke-free legislation, a lightning rod topic in a culture still loyal to a burning weed whose worth had paled in comparison to the cost of its carnage. We were “running wide open” and believed that we were doing important work. 

But then our forward-thinking, appreciative CEO and friend died suddenly, and the open communication and innovation seemingly vanished. Those events inspired my first “retirement.” After this, I became employed for the first time and was blessed once again with a wonderful partner and colleagues. But despite those blessings, the global practice of medicine had begun to change. Physicians were now seen by some as widgets; their worth measured in productivity. A few years in, I needed part-time work to care for my aging parents. My employer needed more, thus inspiring my second “retirement”. 

 

My Second ‘Retirement’

My parents died within 4 months of each other in 2020. Suddenly, I was untethered from both my professional persona and role as caregiver. It was then that my sadness accelerated toward what seemed like the second circle of Hell, with many more to come. 

To many, my sadness made no sense. Our accountant reassured us that we no longer “needed” to work, and I was (and still am) happily married to my high school sweetheart. Our beautiful daughters were healthy and thriving. Although I mouthed appreciation for my blessings in prayer, I could not prevent myself from sinking further. 

My always supportive husband was worried. Tony had skipped happily into his retirement from teaching. He had hoped I would do that same. “You cannot sit on that couch and mope for the rest of your life,” he said, exasperated. 

I thought about doing just that, until one day I answered a phone call to hear, “Doctor, have you ever been to Montana?” Before I could cut her off, the woman charged into the description of a job opening for a locums cardiologist. I immediately sat up. “No office work?” I questioned. 

“No, this is strictly hospital call, rounds, and reading studies.” I didn’t know such jobs existed.

“What is the salary, and what do you cover?” I asked trying to conceal the fact that Tony would have gladly paid her to get me off the couch. 

 

Finding What Suits Me

If I’m honest, since my training days, hospital work is all I have ever wanted. I’ve always felt trapped by the imaginary timer that is part of every office visit. I found running a code less challenging than having to stand and end an office visit that might leave a patient wanting more. 

On hospital days, there are no scheduled time slots. I can triage patients according to their needs. My deadlines are self-imposed: To have a morning coffee with Tony. To deliver the best care possible. To educate as much as time will allow. To beat the midnight clock, after which billing is a little more difficult. 

I will soon begin my seventh year as an inpatient, acute-care cardiologist. Although I was flattered to be considered for full-time work, I couldn’t do that to Tony (who declined to move from Kentucky). We struck a deal that we’d travel to the same facility, where I work seven to nine jobs a year. 

I am now a less anxious “retiree.” My mood is bolstered by the knowledge that within days to weeks I’ll be back to doing what I love: Seeing patients. Making a difference. Enjoying professional comradery and appreciation.

Tony golfs while I work and he jokes that he is a “real go-getter,” explaining that “I take her to work in the morning and then at night, I go get her!” 

For those considering this line of work, it’s not for the faint of heart. My workday can stretch to over 16 hours. But I work in the best of hospital settings. On morning rounds, we present every single patient on the service. Our ER is staffed 100% of the time with at least four board-certified emergency medicine trained physicians. Everyone I work with shares a patient-first philosophy. 

Because of this, I have quite easily ascended from Dante’s inferno. I am happy again in my professional life. 

I know I’ll eventually have to retire for real, and I hope it will be at a time of my choosing and not enforced by the failings of modern medicine. I believe that these past few years will help ease that transition. And when that time comes, I’ll able to look back and know that I was blessed with a long and mostly satisfying career. 

Until then, my magic erasers, colored pencils and gardening will have to wait.

Dr. Walton-Shirley is a clinical cardiologist from Nashville, Tennessee. She reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

I’ve tried to retire from medicine. Really. Proofs of my sincerity include a true retirement from performing procedures and the closing of two office practices. I even attended the wonderful retirement party my daughters threw for me. 

I had great plans for my newfound leisure time. I purchased about a thousand colored pencils to map my family ancestry. I wore out many magic erasers in my cleaning efforts. I cajoled my husband, Tony, to help me build not one, but three, gardens in our yard. Upon realizing I had no more weeds or closets to conquer, I began a Dante-like descent into a dark abyss. I felt my sadness was justified. After all, I had immensely enjoyed my early medical life. 

 

From Private Practice to Being Employed

I had a joint cardiology practice with the great Jim Whiteside, MD, in South Central Kentucky for 24 years. Our schedule was always bursting at the seams in the heart of tobacco country. We opened the first cath lab in our hospital, inspired the purchase of a new nuclear scanner, and expanded the stress echo lab. After a 6-year odyssey, we successfully championed primary PCI without surgery on site (along with Ephraim McDowell Regional Medical Center in Danville, Kentucky). As our services expanded, we remodeled to accommodate three cardiologists and two nurse practitioners. Simultaneously, we lobbied our city council and mayor to pass smoke-free legislation, a lightning rod topic in a culture still loyal to a burning weed whose worth had paled in comparison to the cost of its carnage. We were “running wide open” and believed that we were doing important work. 

But then our forward-thinking, appreciative CEO and friend died suddenly, and the open communication and innovation seemingly vanished. Those events inspired my first “retirement.” After this, I became employed for the first time and was blessed once again with a wonderful partner and colleagues. But despite those blessings, the global practice of medicine had begun to change. Physicians were now seen by some as widgets; their worth measured in productivity. A few years in, I needed part-time work to care for my aging parents. My employer needed more, thus inspiring my second “retirement”. 

 

My Second ‘Retirement’

My parents died within 4 months of each other in 2020. Suddenly, I was untethered from both my professional persona and role as caregiver. It was then that my sadness accelerated toward what seemed like the second circle of Hell, with many more to come. 

To many, my sadness made no sense. Our accountant reassured us that we no longer “needed” to work, and I was (and still am) happily married to my high school sweetheart. Our beautiful daughters were healthy and thriving. Although I mouthed appreciation for my blessings in prayer, I could not prevent myself from sinking further. 

My always supportive husband was worried. Tony had skipped happily into his retirement from teaching. He had hoped I would do that same. “You cannot sit on that couch and mope for the rest of your life,” he said, exasperated. 

I thought about doing just that, until one day I answered a phone call to hear, “Doctor, have you ever been to Montana?” Before I could cut her off, the woman charged into the description of a job opening for a locums cardiologist. I immediately sat up. “No office work?” I questioned. 

“No, this is strictly hospital call, rounds, and reading studies.” I didn’t know such jobs existed.

“What is the salary, and what do you cover?” I asked trying to conceal the fact that Tony would have gladly paid her to get me off the couch. 

 

Finding What Suits Me

If I’m honest, since my training days, hospital work is all I have ever wanted. I’ve always felt trapped by the imaginary timer that is part of every office visit. I found running a code less challenging than having to stand and end an office visit that might leave a patient wanting more. 

On hospital days, there are no scheduled time slots. I can triage patients according to their needs. My deadlines are self-imposed: To have a morning coffee with Tony. To deliver the best care possible. To educate as much as time will allow. To beat the midnight clock, after which billing is a little more difficult. 

I will soon begin my seventh year as an inpatient, acute-care cardiologist. Although I was flattered to be considered for full-time work, I couldn’t do that to Tony (who declined to move from Kentucky). We struck a deal that we’d travel to the same facility, where I work seven to nine jobs a year. 

I am now a less anxious “retiree.” My mood is bolstered by the knowledge that within days to weeks I’ll be back to doing what I love: Seeing patients. Making a difference. Enjoying professional comradery and appreciation.

Tony golfs while I work and he jokes that he is a “real go-getter,” explaining that “I take her to work in the morning and then at night, I go get her!” 

For those considering this line of work, it’s not for the faint of heart. My workday can stretch to over 16 hours. But I work in the best of hospital settings. On morning rounds, we present every single patient on the service. Our ER is staffed 100% of the time with at least four board-certified emergency medicine trained physicians. Everyone I work with shares a patient-first philosophy. 

Because of this, I have quite easily ascended from Dante’s inferno. I am happy again in my professional life. 

I know I’ll eventually have to retire for real, and I hope it will be at a time of my choosing and not enforced by the failings of modern medicine. I believe that these past few years will help ease that transition. And when that time comes, I’ll able to look back and know that I was blessed with a long and mostly satisfying career. 

Until then, my magic erasers, colored pencils and gardening will have to wait.

Dr. Walton-Shirley is a clinical cardiologist from Nashville, Tennessee. She reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

I’ve tried to retire from medicine. Really. Proofs of my sincerity include a true retirement from performing procedures and the closing of two office practices. I even attended the wonderful retirement party my daughters threw for me. 

I had great plans for my newfound leisure time. I purchased about a thousand colored pencils to map my family ancestry. I wore out many magic erasers in my cleaning efforts. I cajoled my husband, Tony, to help me build not one, but three, gardens in our yard. Upon realizing I had no more weeds or closets to conquer, I began a Dante-like descent into a dark abyss. I felt my sadness was justified. After all, I had immensely enjoyed my early medical life. 

 

From Private Practice to Being Employed

I had a joint cardiology practice with the great Jim Whiteside, MD, in South Central Kentucky for 24 years. Our schedule was always bursting at the seams in the heart of tobacco country. We opened the first cath lab in our hospital, inspired the purchase of a new nuclear scanner, and expanded the stress echo lab. After a 6-year odyssey, we successfully championed primary PCI without surgery on site (along with Ephraim McDowell Regional Medical Center in Danville, Kentucky). As our services expanded, we remodeled to accommodate three cardiologists and two nurse practitioners. Simultaneously, we lobbied our city council and mayor to pass smoke-free legislation, a lightning rod topic in a culture still loyal to a burning weed whose worth had paled in comparison to the cost of its carnage. We were “running wide open” and believed that we were doing important work. 

But then our forward-thinking, appreciative CEO and friend died suddenly, and the open communication and innovation seemingly vanished. Those events inspired my first “retirement.” After this, I became employed for the first time and was blessed once again with a wonderful partner and colleagues. But despite those blessings, the global practice of medicine had begun to change. Physicians were now seen by some as widgets; their worth measured in productivity. A few years in, I needed part-time work to care for my aging parents. My employer needed more, thus inspiring my second “retirement”. 

 

My Second ‘Retirement’

My parents died within 4 months of each other in 2020. Suddenly, I was untethered from both my professional persona and role as caregiver. It was then that my sadness accelerated toward what seemed like the second circle of Hell, with many more to come. 

To many, my sadness made no sense. Our accountant reassured us that we no longer “needed” to work, and I was (and still am) happily married to my high school sweetheart. Our beautiful daughters were healthy and thriving. Although I mouthed appreciation for my blessings in prayer, I could not prevent myself from sinking further. 

My always supportive husband was worried. Tony had skipped happily into his retirement from teaching. He had hoped I would do that same. “You cannot sit on that couch and mope for the rest of your life,” he said, exasperated. 

I thought about doing just that, until one day I answered a phone call to hear, “Doctor, have you ever been to Montana?” Before I could cut her off, the woman charged into the description of a job opening for a locums cardiologist. I immediately sat up. “No office work?” I questioned. 

“No, this is strictly hospital call, rounds, and reading studies.” I didn’t know such jobs existed.

“What is the salary, and what do you cover?” I asked trying to conceal the fact that Tony would have gladly paid her to get me off the couch. 

 

Finding What Suits Me

If I’m honest, since my training days, hospital work is all I have ever wanted. I’ve always felt trapped by the imaginary timer that is part of every office visit. I found running a code less challenging than having to stand and end an office visit that might leave a patient wanting more. 

On hospital days, there are no scheduled time slots. I can triage patients according to their needs. My deadlines are self-imposed: To have a morning coffee with Tony. To deliver the best care possible. To educate as much as time will allow. To beat the midnight clock, after which billing is a little more difficult. 

I will soon begin my seventh year as an inpatient, acute-care cardiologist. Although I was flattered to be considered for full-time work, I couldn’t do that to Tony (who declined to move from Kentucky). We struck a deal that we’d travel to the same facility, where I work seven to nine jobs a year. 

I am now a less anxious “retiree.” My mood is bolstered by the knowledge that within days to weeks I’ll be back to doing what I love: Seeing patients. Making a difference. Enjoying professional comradery and appreciation.

Tony golfs while I work and he jokes that he is a “real go-getter,” explaining that “I take her to work in the morning and then at night, I go get her!” 

For those considering this line of work, it’s not for the faint of heart. My workday can stretch to over 16 hours. But I work in the best of hospital settings. On morning rounds, we present every single patient on the service. Our ER is staffed 100% of the time with at least four board-certified emergency medicine trained physicians. Everyone I work with shares a patient-first philosophy. 

Because of this, I have quite easily ascended from Dante’s inferno. I am happy again in my professional life. 

I know I’ll eventually have to retire for real, and I hope it will be at a time of my choosing and not enforced by the failings of modern medicine. I believe that these past few years will help ease that transition. And when that time comes, I’ll able to look back and know that I was blessed with a long and mostly satisfying career. 

Until then, my magic erasers, colored pencils and gardening will have to wait.

Dr. Walton-Shirley is a clinical cardiologist from Nashville, Tennessee. She reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. Paul, what is MASLD?

Paul N. Williams, MD: MASLD is metabolic dysfunction–associated steatotic liver disease. 

Watto: We talked about a really stripped-down way of testing people for MASLD. If we see mildly elevated liver enzymes, what should we be testing, and how does alcohol factor in?

Williams: Before you can make a definitive diagnosis of MASLD, you need to rule out other causes of liver inflammation — things that would cause a patient’s transaminases to increase. Alcohol is synergistic with everything that can harm the liver.

A great place to start is to gauge someone’s alcohol intake to make sure it isn’t causing hepatic inflammation. The phosphatidyl ethanol level is a serologic test to determine chronic, heavy alcohol use. It’s a new kid on the block. I’ve seen it mostly ordered by hepatologists. It is a way of determining whether someone has had fairly consistent alcohol use up to 4 weeks after the fact. The cutoff for a positive test is 20 ng/mL.

Dr Tapper frames the test this way. He isn’t using the test to catch someone in a lie about their alcohol use. He tells patients that he orders this test for all patients with liver inflammation, because alcohol is a common cause. The test helps him better understand the factors that might be affecting the patient’s liver function. 

If the test comes back positive, you can have a conversation about that, and if it’s not positive, you move on to the next possible cause. Other fairly common causes of liver inflammation are relatively easy to address. 

Watto: Instead of ordering ceruloplasmin or alpha-1 antitrypsin tests, for example, the first thing Dr Tapper recommends is checking for hepatitis B and C. We can cure hepatitis C. We can’t cure hepatitis B, but it’s important to know if the patient has it. Primary care physicians should be comfortable ordering these tests. 

Really high ALT levels (eg, in the 200s) don’t usually happen from steatotic liver disease. In those cases, we would send an expanded panel that might include tests for autoimmune hepatitis-ANA, anti–smooth muscle antibody, and IgG levels. Otherwise, most of these patients don’t need much more testing.

What is a FIB4 score and how does that factor in?

Williams: The FIB4 score estimates the degree of fibrosis based on the ALT and AST levels, platelet count, and the patient’s age. These data are plugged into a formula. If the FIB4 score is low (meaning not much fibrosis is present), you can stop there and do your counseling about lifestyle changes and address the reversible factors.

If the FIB4 score is above a certain threshold (1.3 in young adults and 2.0 in older adults), you need to find a more concrete way to determine the degree of fibrosis, typically through imaging. 

Elastography can be done either with ultrasound or MRI. Ultrasound is typically ordered, but Dr Tapper recommends doing MRI on patients with a BMI > 40. Those patients are probably better served by doing MRI to determine the degree of liver fibrosis.

Watto: Patients with low FIB4 scores probably don’t need elastography but those with high FIB4 scores do. For the interpretation of ultrasound-based elastography results, Dr Tapper gave us the “rule of 5s”.

Elastography results are reported in kilopascal (kPa) units. A finding of 5 kPa or less is normal. Forty percent of those with a result of 10 kPa might have advanced liver disease. Above 15 kPa, the likelihood of cirrhosis is high, becoming very likely at 25 kPa. Finally, with a result of > 25 kPa, portal hypertension is likely, and you might need to have a conversation about starting the patient on medicine to prevent variceal bleeding.

We are moving toward more noninvasive testing and avoiding biopsies. We have cutoff values for MRI-based elastography as well. Both of these tests can help stage the liver. 

What can we tell people about diet? 

Williams: Weight loss is helpful. You can reverse fibrosis with weight loss. You can truly help your liver and bring it closer to its healthy baseline with weight loss. A loss of 7.5% body weight can reduce steatohepatitis, and with around 10% of body weight loss, you can actually resolve fibrosis, which is remarkable.

We all know that weight loss can be very therapeutic for many conditions. It’s just very hard to achieve. As primary care doctors, we should use what we have in our armamentarium to achieve that goal. Often, that will include certain medications.

Watto: I like giving patients the 10% number because if they weigh 220 pounds, they need to lose 22 pounds. If they weigh 300 pounds, it’s 30 pounds. Most people who weigh 300 pounds think they need to lose 100 pounds to have any sort of health benefit, but it’s much less than that. So, I do find that helpful.

But now a new drug has been approved. It’s a thyroid memetic called resmetirom. It was from the MAESTRO-NASH trial. Without weight loss, it helped to reverse fibrosis.

This is going to be used more and more in the future. It’s still being worked out exactly where the place is for that drug, so much so that Dr Tapper, as a liver expert, hadn’t even had the chance to prescribe it yet. Of course, it was very recently approved. 

Dr. Tapper is one of our most celebrated guests, so check out the full podcast here.

A version of this article appeared on Medscape.com. 

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. Paul, what is MASLD?

Paul N. Williams, MD: MASLD is metabolic dysfunction–associated steatotic liver disease. 

Watto: We talked about a really stripped-down way of testing people for MASLD. If we see mildly elevated liver enzymes, what should we be testing, and how does alcohol factor in?

Williams: Before you can make a definitive diagnosis of MASLD, you need to rule out other causes of liver inflammation — things that would cause a patient’s transaminases to increase. Alcohol is synergistic with everything that can harm the liver.

A great place to start is to gauge someone’s alcohol intake to make sure it isn’t causing hepatic inflammation. The phosphatidyl ethanol level is a serologic test to determine chronic, heavy alcohol use. It’s a new kid on the block. I’ve seen it mostly ordered by hepatologists. It is a way of determining whether someone has had fairly consistent alcohol use up to 4 weeks after the fact. The cutoff for a positive test is 20 ng/mL.

Dr Tapper frames the test this way. He isn’t using the test to catch someone in a lie about their alcohol use. He tells patients that he orders this test for all patients with liver inflammation, because alcohol is a common cause. The test helps him better understand the factors that might be affecting the patient’s liver function. 

If the test comes back positive, you can have a conversation about that, and if it’s not positive, you move on to the next possible cause. Other fairly common causes of liver inflammation are relatively easy to address. 

Watto: Instead of ordering ceruloplasmin or alpha-1 antitrypsin tests, for example, the first thing Dr Tapper recommends is checking for hepatitis B and C. We can cure hepatitis C. We can’t cure hepatitis B, but it’s important to know if the patient has it. Primary care physicians should be comfortable ordering these tests. 

Really high ALT levels (eg, in the 200s) don’t usually happen from steatotic liver disease. In those cases, we would send an expanded panel that might include tests for autoimmune hepatitis-ANA, anti–smooth muscle antibody, and IgG levels. Otherwise, most of these patients don’t need much more testing.

What is a FIB4 score and how does that factor in?

Williams: The FIB4 score estimates the degree of fibrosis based on the ALT and AST levels, platelet count, and the patient’s age. These data are plugged into a formula. If the FIB4 score is low (meaning not much fibrosis is present), you can stop there and do your counseling about lifestyle changes and address the reversible factors.

If the FIB4 score is above a certain threshold (1.3 in young adults and 2.0 in older adults), you need to find a more concrete way to determine the degree of fibrosis, typically through imaging. 

Elastography can be done either with ultrasound or MRI. Ultrasound is typically ordered, but Dr Tapper recommends doing MRI on patients with a BMI > 40. Those patients are probably better served by doing MRI to determine the degree of liver fibrosis.

Watto: Patients with low FIB4 scores probably don’t need elastography but those with high FIB4 scores do. For the interpretation of ultrasound-based elastography results, Dr Tapper gave us the “rule of 5s”.

Elastography results are reported in kilopascal (kPa) units. A finding of 5 kPa or less is normal. Forty percent of those with a result of 10 kPa might have advanced liver disease. Above 15 kPa, the likelihood of cirrhosis is high, becoming very likely at 25 kPa. Finally, with a result of > 25 kPa, portal hypertension is likely, and you might need to have a conversation about starting the patient on medicine to prevent variceal bleeding.

We are moving toward more noninvasive testing and avoiding biopsies. We have cutoff values for MRI-based elastography as well. Both of these tests can help stage the liver. 

What can we tell people about diet? 

Williams: Weight loss is helpful. You can reverse fibrosis with weight loss. You can truly help your liver and bring it closer to its healthy baseline with weight loss. A loss of 7.5% body weight can reduce steatohepatitis, and with around 10% of body weight loss, you can actually resolve fibrosis, which is remarkable.

We all know that weight loss can be very therapeutic for many conditions. It’s just very hard to achieve. As primary care doctors, we should use what we have in our armamentarium to achieve that goal. Often, that will include certain medications.

Watto: I like giving patients the 10% number because if they weigh 220 pounds, they need to lose 22 pounds. If they weigh 300 pounds, it’s 30 pounds. Most people who weigh 300 pounds think they need to lose 100 pounds to have any sort of health benefit, but it’s much less than that. So, I do find that helpful.

But now a new drug has been approved. It’s a thyroid memetic called resmetirom. It was from the MAESTRO-NASH trial. Without weight loss, it helped to reverse fibrosis.

This is going to be used more and more in the future. It’s still being worked out exactly where the place is for that drug, so much so that Dr Tapper, as a liver expert, hadn’t even had the chance to prescribe it yet. Of course, it was very recently approved. 

Dr. Tapper is one of our most celebrated guests, so check out the full podcast here.

A version of this article appeared on Medscape.com. 

This transcript has been edited for clarity. 

Matthew F. Watto, MD: Welcome back to The Curbsiders. I’m Dr. Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr. Paul Nelson Williams. Paul, what is MASLD?

Paul N. Williams, MD: MASLD is metabolic dysfunction–associated steatotic liver disease. 

Watto: We talked about a really stripped-down way of testing people for MASLD. If we see mildly elevated liver enzymes, what should we be testing, and how does alcohol factor in?

Williams: Before you can make a definitive diagnosis of MASLD, you need to rule out other causes of liver inflammation — things that would cause a patient’s transaminases to increase. Alcohol is synergistic with everything that can harm the liver.

A great place to start is to gauge someone’s alcohol intake to make sure it isn’t causing hepatic inflammation. The phosphatidyl ethanol level is a serologic test to determine chronic, heavy alcohol use. It’s a new kid on the block. I’ve seen it mostly ordered by hepatologists. It is a way of determining whether someone has had fairly consistent alcohol use up to 4 weeks after the fact. The cutoff for a positive test is 20 ng/mL.

Dr Tapper frames the test this way. He isn’t using the test to catch someone in a lie about their alcohol use. He tells patients that he orders this test for all patients with liver inflammation, because alcohol is a common cause. The test helps him better understand the factors that might be affecting the patient’s liver function. 

If the test comes back positive, you can have a conversation about that, and if it’s not positive, you move on to the next possible cause. Other fairly common causes of liver inflammation are relatively easy to address. 

Watto: Instead of ordering ceruloplasmin or alpha-1 antitrypsin tests, for example, the first thing Dr Tapper recommends is checking for hepatitis B and C. We can cure hepatitis C. We can’t cure hepatitis B, but it’s important to know if the patient has it. Primary care physicians should be comfortable ordering these tests. 

Really high ALT levels (eg, in the 200s) don’t usually happen from steatotic liver disease. In those cases, we would send an expanded panel that might include tests for autoimmune hepatitis-ANA, anti–smooth muscle antibody, and IgG levels. Otherwise, most of these patients don’t need much more testing.

What is a FIB4 score and how does that factor in?

Williams: The FIB4 score estimates the degree of fibrosis based on the ALT and AST levels, platelet count, and the patient’s age. These data are plugged into a formula. If the FIB4 score is low (meaning not much fibrosis is present), you can stop there and do your counseling about lifestyle changes and address the reversible factors.

If the FIB4 score is above a certain threshold (1.3 in young adults and 2.0 in older adults), you need to find a more concrete way to determine the degree of fibrosis, typically through imaging. 

Elastography can be done either with ultrasound or MRI. Ultrasound is typically ordered, but Dr Tapper recommends doing MRI on patients with a BMI > 40. Those patients are probably better served by doing MRI to determine the degree of liver fibrosis.

Watto: Patients with low FIB4 scores probably don’t need elastography but those with high FIB4 scores do. For the interpretation of ultrasound-based elastography results, Dr Tapper gave us the “rule of 5s”.

Elastography results are reported in kilopascal (kPa) units. A finding of 5 kPa or less is normal. Forty percent of those with a result of 10 kPa might have advanced liver disease. Above 15 kPa, the likelihood of cirrhosis is high, becoming very likely at 25 kPa. Finally, with a result of > 25 kPa, portal hypertension is likely, and you might need to have a conversation about starting the patient on medicine to prevent variceal bleeding.

We are moving toward more noninvasive testing and avoiding biopsies. We have cutoff values for MRI-based elastography as well. Both of these tests can help stage the liver. 

What can we tell people about diet? 

Williams: Weight loss is helpful. You can reverse fibrosis with weight loss. You can truly help your liver and bring it closer to its healthy baseline with weight loss. A loss of 7.5% body weight can reduce steatohepatitis, and with around 10% of body weight loss, you can actually resolve fibrosis, which is remarkable.

We all know that weight loss can be very therapeutic for many conditions. It’s just very hard to achieve. As primary care doctors, we should use what we have in our armamentarium to achieve that goal. Often, that will include certain medications.

Watto: I like giving patients the 10% number because if they weigh 220 pounds, they need to lose 22 pounds. If they weigh 300 pounds, it’s 30 pounds. Most people who weigh 300 pounds think they need to lose 100 pounds to have any sort of health benefit, but it’s much less than that. So, I do find that helpful.

But now a new drug has been approved. It’s a thyroid memetic called resmetirom. It was from the MAESTRO-NASH trial. Without weight loss, it helped to reverse fibrosis.

This is going to be used more and more in the future. It’s still being worked out exactly where the place is for that drug, so much so that Dr Tapper, as a liver expert, hadn’t even had the chance to prescribe it yet. Of course, it was very recently approved. 

Dr. Tapper is one of our most celebrated guests, so check out the full podcast here.

A version of this article appeared on Medscape.com.