News

Whether coffee is good or bad for health is a frequent debate in the media, fueled by apparently conflicting studies suggesting the plethora of bioactive chemicals in the popular brew could either raise or lower cancer risk.

Now, an analysis by Cambridge scientists has suggested that while coffee is not associated with enhanced overall risk of non–digestive system cancers among people genetically predicted to drink more of it, consumption was associated with a higher risk of digestive system cancers.

Lynda Banzi/MDedge News

That risk was driven by a “strong association” with esophageal cancer, although this might be explained by a tendency for drinking it warm or hot, the study in the journal Clinical Nutrition suggested.

Regular coffee drinking has been linked to a slightly lower risk of all-cause mortality. However, it remains unclear whether coffee consumption is associated with a lower risk of dying from cancer.
 

Hotly debated

In 2016, a working group of international scientists convened by the International Agency for Research on Cancer (IARC) found no conclusive evidence for a carcinogenic effect of drinking coffee. However, the experts did find that drinking very hot beverages was a probable cause of esophageal cancer, making “the temperature, rather than the drinks themselves” the most likely cause, according to the organization’s director.

This latest study concurred. “We provide strong evidence for a causal relationship which is large in magnitude (threefold) and consistent across sensitivity analyses and in a replication study,” it stated.

The Cambridge researchers, assisted by colleagues at the Karolinska Institutet in Stockholm and Bristol Medical School, conducted a Mendelian randomization study to investigate causal associations between coffee consumption and 22 site-specific cancers using data of individuals of European descent in the UK Biobank.

They reported “no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied” (odds ratio [OR], in the main analysis 1.05, 95% confidence interval [CI], 0.98-1.14, P = .183), and remained without association after adjustments for predicted BMI, smoking, or alcohol consumption.

However, genetically predicted coffee consumption was linked to an increased risk of digestive system cancer (OR, 1.28, 95% CI, 1.09-1.51, P = .003), and the risk was largely attributed to “a strong association with esophageal cancer” (OR, 2.79, 95% CI, 1.73-4.50, P = 2.5x10^-5). This risk association remained persistent after adjustment for confounders, the researchers said.
 

Coffee or tea?

Further analysis of the data found that increased risk of esophageal cancer was consistently associated with genetically predicted coffee consumption by individuals with a preference for warm and hot drinks. Among this group, a similar esophageal cancer risk profile among those who reported drinking one to three cups of coffee a day and those who said they did not drink coffee was most likely due to a high prevalence of tea drinking, the study authors said.

“It is, therefore, plausible that a carcinogenic effect of coffee relates to thermal injury broadly, rather than being specific to coffee or its constituents,” said the scientists, who highlighted that this was also pointed out by the IARC in its statement 6 years ago.

Genetically predicted coffee consumption was also found to be associated with increased risk of multiple myeloma (OR, 2.25, 95% CI, 1.30-3.89, P = .004) and reduced ovarian cancer risk (OR, 0.63, 95% CI, 0.43-0.93, P = .020).

The authors concluded there was “evidence for coffee consumption being causally associated with risk of esophageal cancer, with some evidence this is related to a temperature effect.” Otherwise, “our results do not support a linear causal association with the majority of cancer types studied, other than limited evidence for harmful and protective associations with multiple myeloma and ovarian cancers respectively.”

Further studies were needed to investigate “the possible mechanisms of coffee consumption in esophageal carcinogenesis,” they said.

A version of this article first appeared on Medscape UK.

Whether coffee is good or bad for health is a frequent debate in the media, fueled by apparently conflicting studies suggesting the plethora of bioactive chemicals in the popular brew could either raise or lower cancer risk.

Now, an analysis by Cambridge scientists has suggested that while coffee is not associated with enhanced overall risk of non–digestive system cancers among people genetically predicted to drink more of it, consumption was associated with a higher risk of digestive system cancers.

Lynda Banzi/MDedge News

That risk was driven by a “strong association” with esophageal cancer, although this might be explained by a tendency for drinking it warm or hot, the study in the journal Clinical Nutrition suggested.

Regular coffee drinking has been linked to a slightly lower risk of all-cause mortality. However, it remains unclear whether coffee consumption is associated with a lower risk of dying from cancer.
 

Hotly debated

In 2016, a working group of international scientists convened by the International Agency for Research on Cancer (IARC) found no conclusive evidence for a carcinogenic effect of drinking coffee. However, the experts did find that drinking very hot beverages was a probable cause of esophageal cancer, making “the temperature, rather than the drinks themselves” the most likely cause, according to the organization’s director.

This latest study concurred. “We provide strong evidence for a causal relationship which is large in magnitude (threefold) and consistent across sensitivity analyses and in a replication study,” it stated.

The Cambridge researchers, assisted by colleagues at the Karolinska Institutet in Stockholm and Bristol Medical School, conducted a Mendelian randomization study to investigate causal associations between coffee consumption and 22 site-specific cancers using data of individuals of European descent in the UK Biobank.

They reported “no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied” (odds ratio [OR], in the main analysis 1.05, 95% confidence interval [CI], 0.98-1.14, P = .183), and remained without association after adjustments for predicted BMI, smoking, or alcohol consumption.

However, genetically predicted coffee consumption was linked to an increased risk of digestive system cancer (OR, 1.28, 95% CI, 1.09-1.51, P = .003), and the risk was largely attributed to “a strong association with esophageal cancer” (OR, 2.79, 95% CI, 1.73-4.50, P = 2.5x10^-5). This risk association remained persistent after adjustment for confounders, the researchers said.
 

Coffee or tea?

Further analysis of the data found that increased risk of esophageal cancer was consistently associated with genetically predicted coffee consumption by individuals with a preference for warm and hot drinks. Among this group, a similar esophageal cancer risk profile among those who reported drinking one to three cups of coffee a day and those who said they did not drink coffee was most likely due to a high prevalence of tea drinking, the study authors said.

“It is, therefore, plausible that a carcinogenic effect of coffee relates to thermal injury broadly, rather than being specific to coffee or its constituents,” said the scientists, who highlighted that this was also pointed out by the IARC in its statement 6 years ago.

Genetically predicted coffee consumption was also found to be associated with increased risk of multiple myeloma (OR, 2.25, 95% CI, 1.30-3.89, P = .004) and reduced ovarian cancer risk (OR, 0.63, 95% CI, 0.43-0.93, P = .020).

The authors concluded there was “evidence for coffee consumption being causally associated with risk of esophageal cancer, with some evidence this is related to a temperature effect.” Otherwise, “our results do not support a linear causal association with the majority of cancer types studied, other than limited evidence for harmful and protective associations with multiple myeloma and ovarian cancers respectively.”

Further studies were needed to investigate “the possible mechanisms of coffee consumption in esophageal carcinogenesis,” they said.

A version of this article first appeared on Medscape UK.

Whether coffee is good or bad for health is a frequent debate in the media, fueled by apparently conflicting studies suggesting the plethora of bioactive chemicals in the popular brew could either raise or lower cancer risk.

Now, an analysis by Cambridge scientists has suggested that while coffee is not associated with enhanced overall risk of non–digestive system cancers among people genetically predicted to drink more of it, consumption was associated with a higher risk of digestive system cancers.

Lynda Banzi/MDedge News

That risk was driven by a “strong association” with esophageal cancer, although this might be explained by a tendency for drinking it warm or hot, the study in the journal Clinical Nutrition suggested.

Regular coffee drinking has been linked to a slightly lower risk of all-cause mortality. However, it remains unclear whether coffee consumption is associated with a lower risk of dying from cancer.
 

Hotly debated

In 2016, a working group of international scientists convened by the International Agency for Research on Cancer (IARC) found no conclusive evidence for a carcinogenic effect of drinking coffee. However, the experts did find that drinking very hot beverages was a probable cause of esophageal cancer, making “the temperature, rather than the drinks themselves” the most likely cause, according to the organization’s director.

This latest study concurred. “We provide strong evidence for a causal relationship which is large in magnitude (threefold) and consistent across sensitivity analyses and in a replication study,” it stated.

The Cambridge researchers, assisted by colleagues at the Karolinska Institutet in Stockholm and Bristol Medical School, conducted a Mendelian randomization study to investigate causal associations between coffee consumption and 22 site-specific cancers using data of individuals of European descent in the UK Biobank.

They reported “no strong evidence supporting a causal relationship between genetically-predicted coffee consumption and the majority of cancers studied” (odds ratio [OR], in the main analysis 1.05, 95% confidence interval [CI], 0.98-1.14, P = .183), and remained without association after adjustments for predicted BMI, smoking, or alcohol consumption.

However, genetically predicted coffee consumption was linked to an increased risk of digestive system cancer (OR, 1.28, 95% CI, 1.09-1.51, P = .003), and the risk was largely attributed to “a strong association with esophageal cancer” (OR, 2.79, 95% CI, 1.73-4.50, P = 2.5x10^-5). This risk association remained persistent after adjustment for confounders, the researchers said.
 

Coffee or tea?

Further analysis of the data found that increased risk of esophageal cancer was consistently associated with genetically predicted coffee consumption by individuals with a preference for warm and hot drinks. Among this group, a similar esophageal cancer risk profile among those who reported drinking one to three cups of coffee a day and those who said they did not drink coffee was most likely due to a high prevalence of tea drinking, the study authors said.

“It is, therefore, plausible that a carcinogenic effect of coffee relates to thermal injury broadly, rather than being specific to coffee or its constituents,” said the scientists, who highlighted that this was also pointed out by the IARC in its statement 6 years ago.

Genetically predicted coffee consumption was also found to be associated with increased risk of multiple myeloma (OR, 2.25, 95% CI, 1.30-3.89, P = .004) and reduced ovarian cancer risk (OR, 0.63, 95% CI, 0.43-0.93, P = .020).

The authors concluded there was “evidence for coffee consumption being causally associated with risk of esophageal cancer, with some evidence this is related to a temperature effect.” Otherwise, “our results do not support a linear causal association with the majority of cancer types studied, other than limited evidence for harmful and protective associations with multiple myeloma and ovarian cancers respectively.”

Further studies were needed to investigate “the possible mechanisms of coffee consumption in esophageal carcinogenesis,” they said.

A version of this article first appeared on Medscape UK.

People who lift weights understand they’re playing a long game.

Once they get past the “newbie gains” – the quick and exciting increases in muscle strength and size – it takes time, effort, and patience to keep making progress.

Whether they know it or not, they’re also playing the longevity game.

A growing body of research shows that resistance training adds years to both lifespan and “healthspan” – the period of life when we’re in good health.

A 2022 study review from Japanese researchers linked “muscle-strengthening activities” to a 15% lower risk of all-cause mortality.

BeyondImages/Getty Images

Resistance exercise was also linked to a lower risk of cardiovascular disease (17%), cancer (12%), and diabetes (17%).

We’ve known for a long time that strength is an excellent predictor of future health. Lots of research has shown that, if all else is equal, stronger men and women have a much lower risk of dying during a given period than people with less strength.

This new research shows that strength training offers similar protection, regardless of the results of that training. So even if you don’t think you’re getting as strong or as lean as you’d like to be, you should keep it up – because chances are, you’re still helping your health in a big way.
 

How strength training helps as you age

For longevity, strength training seems to be especially effective for older adults, says Roger Fielding, PhD, of Tufts University Medford, Mass., who’s been studying the role of exercise in the aging process since the early 1990s.

“With aging, we see clear deficits in muscle function and bone health,” he says. “That all can be slowed, attenuated, or reversed with appropriate exercise.”

His concept of “appropriate” has changed a lot in the past 3 decades. “When I first started studying this stuff, we would try to give people a very formalized prescription” for strength training, he says.

That strength-training prescription typically included a lot of sets (three per exercise), moderate reps (8-12 per set), and relatively heavy weights. It also required professional supervision in a well-equipped gym, which was both unappealing and impractical for most of the target population.

“What I’ve learned is that even lower-intensity strength training, at home, without a lot of specialized equipment, has some benefits,” he says.

Which benefits? That’s harder to say.

The research linking resistance exercise to lower mortality comes from large, population-wide surveys, looking at tens or even hundreds of thousands of people. The broad category of “muscle-strengthening exercises” can include anything from calisthenics in the living room to a serious bodybuilding or power-lifting program.

They’re also based on self-reporting by the people studied. Because of that, “we should be careful how we interpret some of these studies,” Dr. Fielding says.
 

How much strength training should you do?

That warning seems especially appropriate for the study’s most surprising conclusion: The maximum longevity benefit comes from one or two resistance exercise sessions a week totaling 30-60 minutes.

The study adds that it’s unclear why more strength training would have diminishing or even negative returns.

Robert Linkul, owner of Training the Older Adult in Shingle Springs, Calif., thinks the answer is perfectly clear.

“Less might be more for the beginning lifter,” he says. That’s why his new clients typically begin with two 50-minute workouts a week. But after 3 months, they need to train three times a week to continue seeing gains.

He currently has 14 clients who have been with him at least 16 years. Most of them started in their 50s and are now in their 60s or 70s. If there were any downside to working out more than two times a week, he’s pretty sure he would’ve seen it by now.
 

Live longer and move longer, too

Mr. Linkul says that his training program includes a lot more than lifting. Clients start each workout with 10-15 minutes of mobility and warm-up exercises. That’s followed by 15 minutes of strength training and 15 minutes of high-intensity resistance training (HIRT).

HIRT uses functional exercises – lifting and carrying dumbbells or kettlebells; pushing or pulling a weighted sled – to improve strength and endurance at the same time.

“Most of the clients I get are training for real-life function,” Mr. Linkul says.

Falling is one of their biggest concerns, and for good reason: According to the World Health Organization, it’s the second-leading cause of unintentional injury–related deaths worldwide, behind only traffic accidents.

Their other major concern is losing their independence, which often follows a fall. “They want to feel they’re not near using a cane or a walker or being stuck in a wheelchair,” he says. “The more we train, the further we get from that.”

That’s where strength training offers its most unique advantages, according to a 2019 study from researchers at McMaster University, Hamilton, Ont. Resistance exercise is “particularly potent for maintaining mobility in older adults,” the study says.
 

Training for life

Traditional aerobic exercise also offers many of the same benefits, including longer life and a lower risk of cardiovascular disease, cancer, and diabetes.

But there’s no need to choose one or the other. As a recent study) noted, combining aerobic and strength exercises leads to a lower risk of early death than either of them separately.

Which makes perfect sense to Dr. Fielding.

“Usually, people who’re physically active aren’t just doing strength training alone,” he says. “Some exercise is better than no exercise,” and more is usually better than less. “People have to find things they like to do and want to do and are able to do consistently.”

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

People who lift weights understand they’re playing a long game.

Once they get past the “newbie gains” – the quick and exciting increases in muscle strength and size – it takes time, effort, and patience to keep making progress.

Whether they know it or not, they’re also playing the longevity game.

A growing body of research shows that resistance training adds years to both lifespan and “healthspan” – the period of life when we’re in good health.

A 2022 study review from Japanese researchers linked “muscle-strengthening activities” to a 15% lower risk of all-cause mortality.

BeyondImages/Getty Images

Resistance exercise was also linked to a lower risk of cardiovascular disease (17%), cancer (12%), and diabetes (17%).

We’ve known for a long time that strength is an excellent predictor of future health. Lots of research has shown that, if all else is equal, stronger men and women have a much lower risk of dying during a given period than people with less strength.

This new research shows that strength training offers similar protection, regardless of the results of that training. So even if you don’t think you’re getting as strong or as lean as you’d like to be, you should keep it up – because chances are, you’re still helping your health in a big way.
 

How strength training helps as you age

For longevity, strength training seems to be especially effective for older adults, says Roger Fielding, PhD, of Tufts University Medford, Mass., who’s been studying the role of exercise in the aging process since the early 1990s.

“With aging, we see clear deficits in muscle function and bone health,” he says. “That all can be slowed, attenuated, or reversed with appropriate exercise.”

His concept of “appropriate” has changed a lot in the past 3 decades. “When I first started studying this stuff, we would try to give people a very formalized prescription” for strength training, he says.

That strength-training prescription typically included a lot of sets (three per exercise), moderate reps (8-12 per set), and relatively heavy weights. It also required professional supervision in a well-equipped gym, which was both unappealing and impractical for most of the target population.

“What I’ve learned is that even lower-intensity strength training, at home, without a lot of specialized equipment, has some benefits,” he says.

Which benefits? That’s harder to say.

The research linking resistance exercise to lower mortality comes from large, population-wide surveys, looking at tens or even hundreds of thousands of people. The broad category of “muscle-strengthening exercises” can include anything from calisthenics in the living room to a serious bodybuilding or power-lifting program.

They’re also based on self-reporting by the people studied. Because of that, “we should be careful how we interpret some of these studies,” Dr. Fielding says.
 

How much strength training should you do?

That warning seems especially appropriate for the study’s most surprising conclusion: The maximum longevity benefit comes from one or two resistance exercise sessions a week totaling 30-60 minutes.

The study adds that it’s unclear why more strength training would have diminishing or even negative returns.

Robert Linkul, owner of Training the Older Adult in Shingle Springs, Calif., thinks the answer is perfectly clear.

“Less might be more for the beginning lifter,” he says. That’s why his new clients typically begin with two 50-minute workouts a week. But after 3 months, they need to train three times a week to continue seeing gains.

He currently has 14 clients who have been with him at least 16 years. Most of them started in their 50s and are now in their 60s or 70s. If there were any downside to working out more than two times a week, he’s pretty sure he would’ve seen it by now.
 

Live longer and move longer, too

Mr. Linkul says that his training program includes a lot more than lifting. Clients start each workout with 10-15 minutes of mobility and warm-up exercises. That’s followed by 15 minutes of strength training and 15 minutes of high-intensity resistance training (HIRT).

HIRT uses functional exercises – lifting and carrying dumbbells or kettlebells; pushing or pulling a weighted sled – to improve strength and endurance at the same time.

“Most of the clients I get are training for real-life function,” Mr. Linkul says.

Falling is one of their biggest concerns, and for good reason: According to the World Health Organization, it’s the second-leading cause of unintentional injury–related deaths worldwide, behind only traffic accidents.

Their other major concern is losing their independence, which often follows a fall. “They want to feel they’re not near using a cane or a walker or being stuck in a wheelchair,” he says. “The more we train, the further we get from that.”

That’s where strength training offers its most unique advantages, according to a 2019 study from researchers at McMaster University, Hamilton, Ont. Resistance exercise is “particularly potent for maintaining mobility in older adults,” the study says.
 

Training for life

Traditional aerobic exercise also offers many of the same benefits, including longer life and a lower risk of cardiovascular disease, cancer, and diabetes.

But there’s no need to choose one or the other. As a recent study) noted, combining aerobic and strength exercises leads to a lower risk of early death than either of them separately.

Which makes perfect sense to Dr. Fielding.

“Usually, people who’re physically active aren’t just doing strength training alone,” he says. “Some exercise is better than no exercise,” and more is usually better than less. “People have to find things they like to do and want to do and are able to do consistently.”

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

People who lift weights understand they’re playing a long game.

Once they get past the “newbie gains” – the quick and exciting increases in muscle strength and size – it takes time, effort, and patience to keep making progress.

Whether they know it or not, they’re also playing the longevity game.

A growing body of research shows that resistance training adds years to both lifespan and “healthspan” – the period of life when we’re in good health.

A 2022 study review from Japanese researchers linked “muscle-strengthening activities” to a 15% lower risk of all-cause mortality.

BeyondImages/Getty Images

Resistance exercise was also linked to a lower risk of cardiovascular disease (17%), cancer (12%), and diabetes (17%).

We’ve known for a long time that strength is an excellent predictor of future health. Lots of research has shown that, if all else is equal, stronger men and women have a much lower risk of dying during a given period than people with less strength.

This new research shows that strength training offers similar protection, regardless of the results of that training. So even if you don’t think you’re getting as strong or as lean as you’d like to be, you should keep it up – because chances are, you’re still helping your health in a big way.
 

How strength training helps as you age

For longevity, strength training seems to be especially effective for older adults, says Roger Fielding, PhD, of Tufts University Medford, Mass., who’s been studying the role of exercise in the aging process since the early 1990s.

“With aging, we see clear deficits in muscle function and bone health,” he says. “That all can be slowed, attenuated, or reversed with appropriate exercise.”

His concept of “appropriate” has changed a lot in the past 3 decades. “When I first started studying this stuff, we would try to give people a very formalized prescription” for strength training, he says.

That strength-training prescription typically included a lot of sets (three per exercise), moderate reps (8-12 per set), and relatively heavy weights. It also required professional supervision in a well-equipped gym, which was both unappealing and impractical for most of the target population.

“What I’ve learned is that even lower-intensity strength training, at home, without a lot of specialized equipment, has some benefits,” he says.

Which benefits? That’s harder to say.

The research linking resistance exercise to lower mortality comes from large, population-wide surveys, looking at tens or even hundreds of thousands of people. The broad category of “muscle-strengthening exercises” can include anything from calisthenics in the living room to a serious bodybuilding or power-lifting program.

They’re also based on self-reporting by the people studied. Because of that, “we should be careful how we interpret some of these studies,” Dr. Fielding says.
 

How much strength training should you do?

That warning seems especially appropriate for the study’s most surprising conclusion: The maximum longevity benefit comes from one or two resistance exercise sessions a week totaling 30-60 minutes.

The study adds that it’s unclear why more strength training would have diminishing or even negative returns.

Robert Linkul, owner of Training the Older Adult in Shingle Springs, Calif., thinks the answer is perfectly clear.

“Less might be more for the beginning lifter,” he says. That’s why his new clients typically begin with two 50-minute workouts a week. But after 3 months, they need to train three times a week to continue seeing gains.

He currently has 14 clients who have been with him at least 16 years. Most of them started in their 50s and are now in their 60s or 70s. If there were any downside to working out more than two times a week, he’s pretty sure he would’ve seen it by now.
 

Live longer and move longer, too

Mr. Linkul says that his training program includes a lot more than lifting. Clients start each workout with 10-15 minutes of mobility and warm-up exercises. That’s followed by 15 minutes of strength training and 15 minutes of high-intensity resistance training (HIRT).

HIRT uses functional exercises – lifting and carrying dumbbells or kettlebells; pushing or pulling a weighted sled – to improve strength and endurance at the same time.

“Most of the clients I get are training for real-life function,” Mr. Linkul says.

Falling is one of their biggest concerns, and for good reason: According to the World Health Organization, it’s the second-leading cause of unintentional injury–related deaths worldwide, behind only traffic accidents.

Their other major concern is losing their independence, which often follows a fall. “They want to feel they’re not near using a cane or a walker or being stuck in a wheelchair,” he says. “The more we train, the further we get from that.”

That’s where strength training offers its most unique advantages, according to a 2019 study from researchers at McMaster University, Hamilton, Ont. Resistance exercise is “particularly potent for maintaining mobility in older adults,” the study says.
 

Training for life

Traditional aerobic exercise also offers many of the same benefits, including longer life and a lower risk of cardiovascular disease, cancer, and diabetes.

But there’s no need to choose one or the other. As a recent study) noted, combining aerobic and strength exercises leads to a lower risk of early death than either of them separately.

Which makes perfect sense to Dr. Fielding.

“Usually, people who’re physically active aren’t just doing strength training alone,” he says. “Some exercise is better than no exercise,” and more is usually better than less. “People have to find things they like to do and want to do and are able to do consistently.”

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

The unfortunate death of Lori McClintock, wife of northern California congressman Tom McClintock, shortly after consuming the herbal remedy white mulberry leaf on Dec. 15, 2021, gives us the opportunity to discuss how to better protect the American public from nutritional supplements with claims to aid health. Mulberry leaf has been purported to lower blood glucose levels, cholesterol, and inflammation as well as promote weight loss.

Many people desire to improve their health with concoctions purported to be “natural” or “from nature” instead of seeing a doctor and taking a medication or other therapy that is evidenced-based and backed by approval from the Food and Drug Administration. With the burgeoning prevalence of obesity and type 2 diabetes in this country (and worldwide) and the lack of a magic bullet that can stop the progression of these life-threatening diseases, many Americans turn to herbal and nutritional supplements that claim to promote weight loss and improve health.

Passed in 1994, the Dietary Supplement Health and Education Act (DSHEA) has allowed manufacturers of herbal and nutritional supplements to be “off the radar” of government regulators, unless their products have been shown to do harm – which is the government’s burden to prove.

A dietary supplement is defined as a product containing one or more vitamin, mineral, herb, or other botanical; amino acid; or other substance that would increase the total dietary intake of that product.

DSHEA exempted dietary supplements from the rigorous safety and efficacy testing that medications must undergo for various disease states, which is regulated by the FDA.
 

People with obesity may fall prey to dietary supplements’ claims

Persons suffering from obesity and its metabolic sequelae may be susceptible to the claims of dietary supplements because:

• The stigma associated with obesity, including the lack of understanding that obesity is a disease not under a person’s control, may make those with the disease wish to remedy it on their own out of shame and peer pressure.
• Clinicians and doctors traditionally have not been trained in obesity medicine so they aren’t comfortable treating obesity.
• It’s only fairly recently that obesity was recognized as a disease, so many insurance companies still don’t reimburse for obesity treatments, including the agents that can suppress appetite and result in weight loss.

For all of these reasons and more, only 2% or less of the millions of Americans suffering from obesity are treated with an antiobesity agent each year.

This has paved the way for the dietary supplement industry to prey on a desperate population, in much the same way that fad diets continue to attract multitudes of Americans. These supplements, however, carry much more risk than fad diets.

The solution, of course, is better regulation of the supplement industry, but it’s also improvement of how obesity is treated by the medical community.
 

How can clinicians and the community help?

Government, academic, community, clinical, and lay persons are more frequently recognizing obesity as a disease. Stigma will slowly come to a halt, as it has for other diseases such as depression and addiction to alcohol and drugs. Medications that have undergone rigorous testing for safety and efficacy eventually will be prescribed more and covered by healthcare insurance. Clinicians, and specifically physicians, are the most trusted persons in terms of giving medical advice. We need to ask patients whether they are taking supplements and be vocal about their lack of protection against harm, as allowed by DSHEA.

It would not be overkill to add prompts to the medical record to ask patients not only about smoking, alcohol, and drug use but also about supplements of all kinds. Some medical records do use these prompts but they are not as ubiquitous as those for smoking, alcohol, and drug use.

The supplement industry is powerful, but so is the medical industry when it comes to lobbying for change. It is ironic that Lori McClintock was the wife of a congressman. Perhaps the silver lining is future work toward legislation advocating for an end to these tragic deaths from poorly regulated supplements. Alignment with government in pushing for stricter regulations could save lives in the future.

Dr. Apovian is a faculty member, department of medicine, division of endocrinology, diabetes, and hypertension; and codirector, Center for Weight Management and Wellness, Boston. She disclosed ties with Abbott, Allergan, Altimmune, Bariatrix Nutrition, Cowen and Company, Curavit, Rhythm Pharma, Jazz, Nutrisystem, Roman, Novo Nordisk, EnteroMedics, Gelesis Srl, Zafgen, Xeno, L-Nutra, Tivity, and Real Appeal.



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

The unfortunate death of Lori McClintock, wife of northern California congressman Tom McClintock, shortly after consuming the herbal remedy white mulberry leaf on Dec. 15, 2021, gives us the opportunity to discuss how to better protect the American public from nutritional supplements with claims to aid health. Mulberry leaf has been purported to lower blood glucose levels, cholesterol, and inflammation as well as promote weight loss.

Many people desire to improve their health with concoctions purported to be “natural” or “from nature” instead of seeing a doctor and taking a medication or other therapy that is evidenced-based and backed by approval from the Food and Drug Administration. With the burgeoning prevalence of obesity and type 2 diabetes in this country (and worldwide) and the lack of a magic bullet that can stop the progression of these life-threatening diseases, many Americans turn to herbal and nutritional supplements that claim to promote weight loss and improve health.

Passed in 1994, the Dietary Supplement Health and Education Act (DSHEA) has allowed manufacturers of herbal and nutritional supplements to be “off the radar” of government regulators, unless their products have been shown to do harm – which is the government’s burden to prove.

A dietary supplement is defined as a product containing one or more vitamin, mineral, herb, or other botanical; amino acid; or other substance that would increase the total dietary intake of that product.

DSHEA exempted dietary supplements from the rigorous safety and efficacy testing that medications must undergo for various disease states, which is regulated by the FDA.
 

People with obesity may fall prey to dietary supplements’ claims

Persons suffering from obesity and its metabolic sequelae may be susceptible to the claims of dietary supplements because:

• The stigma associated with obesity, including the lack of understanding that obesity is a disease not under a person’s control, may make those with the disease wish to remedy it on their own out of shame and peer pressure.
• Clinicians and doctors traditionally have not been trained in obesity medicine so they aren’t comfortable treating obesity.
• It’s only fairly recently that obesity was recognized as a disease, so many insurance companies still don’t reimburse for obesity treatments, including the agents that can suppress appetite and result in weight loss.

For all of these reasons and more, only 2% or less of the millions of Americans suffering from obesity are treated with an antiobesity agent each year.

This has paved the way for the dietary supplement industry to prey on a desperate population, in much the same way that fad diets continue to attract multitudes of Americans. These supplements, however, carry much more risk than fad diets.

The solution, of course, is better regulation of the supplement industry, but it’s also improvement of how obesity is treated by the medical community.
 

How can clinicians and the community help?

Government, academic, community, clinical, and lay persons are more frequently recognizing obesity as a disease. Stigma will slowly come to a halt, as it has for other diseases such as depression and addiction to alcohol and drugs. Medications that have undergone rigorous testing for safety and efficacy eventually will be prescribed more and covered by healthcare insurance. Clinicians, and specifically physicians, are the most trusted persons in terms of giving medical advice. We need to ask patients whether they are taking supplements and be vocal about their lack of protection against harm, as allowed by DSHEA.

It would not be overkill to add prompts to the medical record to ask patients not only about smoking, alcohol, and drug use but also about supplements of all kinds. Some medical records do use these prompts but they are not as ubiquitous as those for smoking, alcohol, and drug use.

The supplement industry is powerful, but so is the medical industry when it comes to lobbying for change. It is ironic that Lori McClintock was the wife of a congressman. Perhaps the silver lining is future work toward legislation advocating for an end to these tragic deaths from poorly regulated supplements. Alignment with government in pushing for stricter regulations could save lives in the future.

Dr. Apovian is a faculty member, department of medicine, division of endocrinology, diabetes, and hypertension; and codirector, Center for Weight Management and Wellness, Boston. She disclosed ties with Abbott, Allergan, Altimmune, Bariatrix Nutrition, Cowen and Company, Curavit, Rhythm Pharma, Jazz, Nutrisystem, Roman, Novo Nordisk, EnteroMedics, Gelesis Srl, Zafgen, Xeno, L-Nutra, Tivity, and Real Appeal.



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

The unfortunate death of Lori McClintock, wife of northern California congressman Tom McClintock, shortly after consuming the herbal remedy white mulberry leaf on Dec. 15, 2021, gives us the opportunity to discuss how to better protect the American public from nutritional supplements with claims to aid health. Mulberry leaf has been purported to lower blood glucose levels, cholesterol, and inflammation as well as promote weight loss.

Many people desire to improve their health with concoctions purported to be “natural” or “from nature” instead of seeing a doctor and taking a medication or other therapy that is evidenced-based and backed by approval from the Food and Drug Administration. With the burgeoning prevalence of obesity and type 2 diabetes in this country (and worldwide) and the lack of a magic bullet that can stop the progression of these life-threatening diseases, many Americans turn to herbal and nutritional supplements that claim to promote weight loss and improve health.

Passed in 1994, the Dietary Supplement Health and Education Act (DSHEA) has allowed manufacturers of herbal and nutritional supplements to be “off the radar” of government regulators, unless their products have been shown to do harm – which is the government’s burden to prove.

A dietary supplement is defined as a product containing one or more vitamin, mineral, herb, or other botanical; amino acid; or other substance that would increase the total dietary intake of that product.

DSHEA exempted dietary supplements from the rigorous safety and efficacy testing that medications must undergo for various disease states, which is regulated by the FDA.
 

People with obesity may fall prey to dietary supplements’ claims

Persons suffering from obesity and its metabolic sequelae may be susceptible to the claims of dietary supplements because:

• The stigma associated with obesity, including the lack of understanding that obesity is a disease not under a person’s control, may make those with the disease wish to remedy it on their own out of shame and peer pressure.
• Clinicians and doctors traditionally have not been trained in obesity medicine so they aren’t comfortable treating obesity.
• It’s only fairly recently that obesity was recognized as a disease, so many insurance companies still don’t reimburse for obesity treatments, including the agents that can suppress appetite and result in weight loss.

For all of these reasons and more, only 2% or less of the millions of Americans suffering from obesity are treated with an antiobesity agent each year.

This has paved the way for the dietary supplement industry to prey on a desperate population, in much the same way that fad diets continue to attract multitudes of Americans. These supplements, however, carry much more risk than fad diets.

The solution, of course, is better regulation of the supplement industry, but it’s also improvement of how obesity is treated by the medical community.
 

How can clinicians and the community help?

Government, academic, community, clinical, and lay persons are more frequently recognizing obesity as a disease. Stigma will slowly come to a halt, as it has for other diseases such as depression and addiction to alcohol and drugs. Medications that have undergone rigorous testing for safety and efficacy eventually will be prescribed more and covered by healthcare insurance. Clinicians, and specifically physicians, are the most trusted persons in terms of giving medical advice. We need to ask patients whether they are taking supplements and be vocal about their lack of protection against harm, as allowed by DSHEA.

It would not be overkill to add prompts to the medical record to ask patients not only about smoking, alcohol, and drug use but also about supplements of all kinds. Some medical records do use these prompts but they are not as ubiquitous as those for smoking, alcohol, and drug use.

The supplement industry is powerful, but so is the medical industry when it comes to lobbying for change. It is ironic that Lori McClintock was the wife of a congressman. Perhaps the silver lining is future work toward legislation advocating for an end to these tragic deaths from poorly regulated supplements. Alignment with government in pushing for stricter regulations could save lives in the future.

Dr. Apovian is a faculty member, department of medicine, division of endocrinology, diabetes, and hypertension; and codirector, Center for Weight Management and Wellness, Boston. She disclosed ties with Abbott, Allergan, Altimmune, Bariatrix Nutrition, Cowen and Company, Curavit, Rhythm Pharma, Jazz, Nutrisystem, Roman, Novo Nordisk, EnteroMedics, Gelesis Srl, Zafgen, Xeno, L-Nutra, Tivity, and Real Appeal.



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

Both yoga and cognitive-behavioral therapy (CBT) provide meaningful improvements in worry, anxiety, and insomnia in older adults that last even 6 months after discontinuing treatment, new research suggests.

The study is the first to compare the long-term effects from the two interventions; and the results offer clinicians and patients two effective choices for reducing worry and anxiety, researchers noted.

“Anxiety can be a really big problem for older adults,” lead investigator Suzanne Danhauer, PhD, professor of social sciences and health policy at Wake Forest University, Winston-Salem, N.C., said in an interview.

“So to find something they can do that lasts ... and has some enduring impact on their quality of life and their mental health, and they’re both nonpharmacologic treatments, I think for a lot of older people that’s really attractive,” Dr. Danhauer said.

The findings are published in the September issue of the American Journal of Geriatric Psychiatry.
 

Long-term benefits

The two-stage randomized preference trial included 500 community-dwelling individuals over age 60 who scored 26 or above on the Penn State Worry Questionnaire–Abbreviated (PSWQ-A), indicating heightened anxiety and worry.

Half the group took part in a randomized, controlled trial comparing CBT (n = 125) with yoga (n = 125). The other half participated in a preference trial where they were allowed to choose between CBT (n = 120) and yoga (n = 130).

Participants completed 20 yoga sessions over 10 weeks or 10 weekly CBT calls between May 2017 and November 2018.

Measures used included the PSWQ-A, the Insomnia Severity Index (ISI), the Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 – Anxiety 8a, and the PROMIS-29 to assess depression, fatigue, physical function, social participation, and pain.

In 2020, the researchers published results at 11 weeks showing improvements from baseline in all areas. The scores for anxiety and worry were similar between the CBT and yoga groups, but CBT yielded significantly higher improvement in insomnia.

At 37 weeks, about 6 months after the interventions had ended, the investigators found even greater improvements from baseline in all areas measured – except physical function.

However, at that point, there were no significant differences between the two interventions in either the randomized controlled trial or the preference trial. There were also no differences in the results between the two trial designs.

“There were some little differences, but by and large we found both interventions to be efficacious,” Dr. Danhauer said. “This gives clinicians [the] choice to be able to say, ‘you can try either one of these and they’re probably going to help.’ ”
 

Beyond statistically significant

The researchers also found the improvements were not just statistically significant, but were also clinically meaningful for worry, anxiety, and insomnia.

Meaningful changes were defined as a decrease of at least 5.5 points on the PSWQ-A for worry, a decrease of at least 3 points on the PROMIS Anxiety scale for anxiety, and a decrease of at least 6 points in the ISI for insomnia.

At long-term follow-up, the majority of participants in both the CBT and yoga arms of the randomized, controlled trial demonstrated meaningful change in worry (85.7% and 77.6%, respectively), anxiety (82.1% and 80.8%), and insomnia (52.8% and 44.3%).

The majority of participants also reported meaningful improvements in generalized anxiety symptoms, depressive symptoms, and fatigue, but not for physical function, pain interference, or pain intensity.

“That’s the part to me that’s particularly notable. The improvements weren’t just statistically significant, they were clinically meaningful as well,” Dr. Danhauer said.

“When it comes right down to people’s lives, they want differences they can feel and see and not just what a P value looks like,” she added.
 

Real-world impact

In an accompanying editorial, Carmen Andreescu, MD, associate professor of psychiatry at the University of Pittsburgh, agreed that the results have “real-world impact.”

“Clinicians can direct their patients toward interventions that may be beneficial, consolidate the results over time and avoid fueling the well-trained worry cognitive loop with concerns related to potential side effects,” Dr. Andreescu wrote.

She adds that interventions such as these “may increase accessibility and provide relief for the immediate suffering of our patients.”

The study was funded by the Patient-Centered Outcomes Research Institute Program. Dr. Danhauer and Dr. Andreescu reported no relevant financial relationships.

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

Both yoga and cognitive-behavioral therapy (CBT) provide meaningful improvements in worry, anxiety, and insomnia in older adults that last even 6 months after discontinuing treatment, new research suggests.

The study is the first to compare the long-term effects from the two interventions; and the results offer clinicians and patients two effective choices for reducing worry and anxiety, researchers noted.

“Anxiety can be a really big problem for older adults,” lead investigator Suzanne Danhauer, PhD, professor of social sciences and health policy at Wake Forest University, Winston-Salem, N.C., said in an interview.

“So to find something they can do that lasts ... and has some enduring impact on their quality of life and their mental health, and they’re both nonpharmacologic treatments, I think for a lot of older people that’s really attractive,” Dr. Danhauer said.

The findings are published in the September issue of the American Journal of Geriatric Psychiatry.
 

Long-term benefits

The two-stage randomized preference trial included 500 community-dwelling individuals over age 60 who scored 26 or above on the Penn State Worry Questionnaire–Abbreviated (PSWQ-A), indicating heightened anxiety and worry.

Half the group took part in a randomized, controlled trial comparing CBT (n = 125) with yoga (n = 125). The other half participated in a preference trial where they were allowed to choose between CBT (n = 120) and yoga (n = 130).

Participants completed 20 yoga sessions over 10 weeks or 10 weekly CBT calls between May 2017 and November 2018.

Measures used included the PSWQ-A, the Insomnia Severity Index (ISI), the Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 – Anxiety 8a, and the PROMIS-29 to assess depression, fatigue, physical function, social participation, and pain.

In 2020, the researchers published results at 11 weeks showing improvements from baseline in all areas. The scores for anxiety and worry were similar between the CBT and yoga groups, but CBT yielded significantly higher improvement in insomnia.

At 37 weeks, about 6 months after the interventions had ended, the investigators found even greater improvements from baseline in all areas measured – except physical function.

However, at that point, there were no significant differences between the two interventions in either the randomized controlled trial or the preference trial. There were also no differences in the results between the two trial designs.

“There were some little differences, but by and large we found both interventions to be efficacious,” Dr. Danhauer said. “This gives clinicians [the] choice to be able to say, ‘you can try either one of these and they’re probably going to help.’ ”
 

Beyond statistically significant

The researchers also found the improvements were not just statistically significant, but were also clinically meaningful for worry, anxiety, and insomnia.

Meaningful changes were defined as a decrease of at least 5.5 points on the PSWQ-A for worry, a decrease of at least 3 points on the PROMIS Anxiety scale for anxiety, and a decrease of at least 6 points in the ISI for insomnia.

At long-term follow-up, the majority of participants in both the CBT and yoga arms of the randomized, controlled trial demonstrated meaningful change in worry (85.7% and 77.6%, respectively), anxiety (82.1% and 80.8%), and insomnia (52.8% and 44.3%).

The majority of participants also reported meaningful improvements in generalized anxiety symptoms, depressive symptoms, and fatigue, but not for physical function, pain interference, or pain intensity.

“That’s the part to me that’s particularly notable. The improvements weren’t just statistically significant, they were clinically meaningful as well,” Dr. Danhauer said.

“When it comes right down to people’s lives, they want differences they can feel and see and not just what a P value looks like,” she added.
 

Real-world impact

In an accompanying editorial, Carmen Andreescu, MD, associate professor of psychiatry at the University of Pittsburgh, agreed that the results have “real-world impact.”

“Clinicians can direct their patients toward interventions that may be beneficial, consolidate the results over time and avoid fueling the well-trained worry cognitive loop with concerns related to potential side effects,” Dr. Andreescu wrote.

She adds that interventions such as these “may increase accessibility and provide relief for the immediate suffering of our patients.”

The study was funded by the Patient-Centered Outcomes Research Institute Program. Dr. Danhauer and Dr. Andreescu reported no relevant financial relationships.

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

Both yoga and cognitive-behavioral therapy (CBT) provide meaningful improvements in worry, anxiety, and insomnia in older adults that last even 6 months after discontinuing treatment, new research suggests.

The study is the first to compare the long-term effects from the two interventions; and the results offer clinicians and patients two effective choices for reducing worry and anxiety, researchers noted.

“Anxiety can be a really big problem for older adults,” lead investigator Suzanne Danhauer, PhD, professor of social sciences and health policy at Wake Forest University, Winston-Salem, N.C., said in an interview.

“So to find something they can do that lasts ... and has some enduring impact on their quality of life and their mental health, and they’re both nonpharmacologic treatments, I think for a lot of older people that’s really attractive,” Dr. Danhauer said.

The findings are published in the September issue of the American Journal of Geriatric Psychiatry.
 

Long-term benefits

The two-stage randomized preference trial included 500 community-dwelling individuals over age 60 who scored 26 or above on the Penn State Worry Questionnaire–Abbreviated (PSWQ-A), indicating heightened anxiety and worry.

Half the group took part in a randomized, controlled trial comparing CBT (n = 125) with yoga (n = 125). The other half participated in a preference trial where they were allowed to choose between CBT (n = 120) and yoga (n = 130).

Participants completed 20 yoga sessions over 10 weeks or 10 weekly CBT calls between May 2017 and November 2018.

Measures used included the PSWQ-A, the Insomnia Severity Index (ISI), the Patient Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 – Anxiety 8a, and the PROMIS-29 to assess depression, fatigue, physical function, social participation, and pain.

In 2020, the researchers published results at 11 weeks showing improvements from baseline in all areas. The scores for anxiety and worry were similar between the CBT and yoga groups, but CBT yielded significantly higher improvement in insomnia.

At 37 weeks, about 6 months after the interventions had ended, the investigators found even greater improvements from baseline in all areas measured – except physical function.

However, at that point, there were no significant differences between the two interventions in either the randomized controlled trial or the preference trial. There were also no differences in the results between the two trial designs.

“There were some little differences, but by and large we found both interventions to be efficacious,” Dr. Danhauer said. “This gives clinicians [the] choice to be able to say, ‘you can try either one of these and they’re probably going to help.’ ”
 

Beyond statistically significant

The researchers also found the improvements were not just statistically significant, but were also clinically meaningful for worry, anxiety, and insomnia.

Meaningful changes were defined as a decrease of at least 5.5 points on the PSWQ-A for worry, a decrease of at least 3 points on the PROMIS Anxiety scale for anxiety, and a decrease of at least 6 points in the ISI for insomnia.

At long-term follow-up, the majority of participants in both the CBT and yoga arms of the randomized, controlled trial demonstrated meaningful change in worry (85.7% and 77.6%, respectively), anxiety (82.1% and 80.8%), and insomnia (52.8% and 44.3%).

The majority of participants also reported meaningful improvements in generalized anxiety symptoms, depressive symptoms, and fatigue, but not for physical function, pain interference, or pain intensity.

“That’s the part to me that’s particularly notable. The improvements weren’t just statistically significant, they were clinically meaningful as well,” Dr. Danhauer said.

“When it comes right down to people’s lives, they want differences they can feel and see and not just what a P value looks like,” she added.
 

Real-world impact

In an accompanying editorial, Carmen Andreescu, MD, associate professor of psychiatry at the University of Pittsburgh, agreed that the results have “real-world impact.”

“Clinicians can direct their patients toward interventions that may be beneficial, consolidate the results over time and avoid fueling the well-trained worry cognitive loop with concerns related to potential side effects,” Dr. Andreescu wrote.

She adds that interventions such as these “may increase accessibility and provide relief for the immediate suffering of our patients.”

The study was funded by the Patient-Centered Outcomes Research Institute Program. Dr. Danhauer and Dr. Andreescu reported no relevant financial relationships.

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

Warning labels on alcoholic products need to be updated to spell out details of potential harm in order to make them more effective, two U.S. researchers have said.

The current labeling, which has not changed for 30 years, focuses on risks during pregnancy and with operating machinery and includes a vague statement that alcohol “may cause health problems.”

This is “so understated that it borders on being misleading,” the two researchers argued.

The science related to the use of alcohol has moved on, and there is now firm evidence of harm. Alcohol has been classified by the International Agency for Research on Cancer (IARC)  as a group 1 carcinogen and has been linked to an increased risk of many types of cancer. Drinking alcohol has also been linked to a wide range of other diseases, from liver disease to pancreatitis to some types of heart disease, the authors noted.

Yet the general public is mostly unaware of the most serious health risks that are associated with alcohol consumption, they pointed out.

“We believe Americans deserve the opportunity to make well-informed decisions about their alcohol consumption,” said Anna H. Grummon, PhD, of the Harvard T. H. Chan School of Public Health, Boston, and Marissa G. Hall, PhD, of the University of North Carolina at Chapel Hill.

“Designing and adopting new alcohol warning labels should therefore be a research and policy priority,” they added.

The two researchers set out their arguments in a perspective article published in The New England Journal of Medicine.

“Alcohol consumption and its associated harms are reaching a crisis point in the United States,” they pointed out.

It now accounts for more than 140,000 deaths per year in the United States, according to the latest data from the Centers for Disease Control and Prevention. The COVID-19 pandemic has made the problem even worse – there was a 25% increase in alcohol-related deaths during 2020.

New, well-designed warning labels on alcohol is a common sense strategy for providing consumers with information and reducing the burden of alcohol-related harm, the authors suggested.
 

Warning Labels Prominently Displayed

Warning labels are most effective when they are prominently displayed, when they include pictures of some type, and when the messages alternate so as to avoid any one message from becoming “stale,” the authors noted. This approach has worked well with cigarette packs. This type of warning has increased smoking quit rates in comparison with smaller, side-of-pack, text-only warning labels.

There is some evidence that this type of labeling can be effective for alcohol. When large, pictorial warnings about cancer risk were temporarily added to the front of alcohol containers in some stores in Yukon, Canada, alcohol sales declined by 6%-10%, they pointed out.

However, pressure from the alcohol industry led to changes in the Yukon project, and while a general health warning remains, the label about increased cancer risk was removed.

The alcohol industry has tried to suppress efforts to educate the public, and this has created problems in conveying health information to consumers, the authors noted. The industry spends more than $1 billion each year to market its products in the United States.

The authors caution that without government intervention, the alcohol industry has little incentive to communicate the risks.

Some companies even link their products to health campaigns, such as selling pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast cancer research, despite compelling evidence linking alcohol to an increased risk of breast cancer.
 

Petition at Congress calling for new labels

This is not the first call for a change in the warning labels on alcohol.

Last year, a number of medical groups petitioned Congress for a new cancer-specific warning label to be displayed on all alcoholic beverages.

The petition was signed by the American Society of Clinical Oncology (ASCO), the American Institute for Cancer Research (AICR), and Breast Cancer Prevention Partners, in collaboration with the American Public Health Association, the Consumer Federation of America, the Center for Science in the Public Interest, Alcohol Justice, and the U.S. Alcohol Policy Alliance.

They are advocating for a label that would say: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

That petition is still pending, Melissa Maitin-Shepard, MPP, policy expert at the AICR, said in an interview.

In addition, the AICR is “working to advocate for the addition of a cancer warning label to alcoholic beverages through multiple channels,” she said. “Given the strong evidence linking alcohol use with at least six types of cancer – and low awareness of the alcohol and cancer connection – there is a tremendous need to educate the public about alcohol and cancer risk.”

Noelle K. LoConte, MD, associate professor of medicine at the University of Wisconsin, Madison, who is the lead author of ASCO’s statement on alcohol and cancer risk, emphasized that there is no doubt that alcohol is a carcinogen, that it causes about 5% of cancers globally, and that its use has increased during the pandemic.

“Initiatives that raise awareness around this issue could help generate more public support for policies that limit alcohol access and thereby decrease the number of alcohol-associated cancers,” she said. “In ASCO’s statement on alcohol and cancer, we recommend several key strategies to reduce high-risk alcohol consumption, including limiting youth access to alcohol, giving municipalities more control over alcohol outlet density and points of sale, and increasing taxes on alcohol.”

However, she also had a small criticism of one point in the NEJM article. It shows a sample infographic that lists gastric cancer as being caused by alcohol. “But as of today, gastric cancer is not on the IARC list of alcohol-associated cancers,” she said. “I think this brings to mind one critical point, that these warning labels have to contain scientifically established facts.”

Dr. Grummon and Dr. Hall have disclosed no relevant financial relationships.

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

Warning labels on alcoholic products need to be updated to spell out details of potential harm in order to make them more effective, two U.S. researchers have said.

The current labeling, which has not changed for 30 years, focuses on risks during pregnancy and with operating machinery and includes a vague statement that alcohol “may cause health problems.”

This is “so understated that it borders on being misleading,” the two researchers argued.

The science related to the use of alcohol has moved on, and there is now firm evidence of harm. Alcohol has been classified by the International Agency for Research on Cancer (IARC)  as a group 1 carcinogen and has been linked to an increased risk of many types of cancer. Drinking alcohol has also been linked to a wide range of other diseases, from liver disease to pancreatitis to some types of heart disease, the authors noted.

Yet the general public is mostly unaware of the most serious health risks that are associated with alcohol consumption, they pointed out.

“We believe Americans deserve the opportunity to make well-informed decisions about their alcohol consumption,” said Anna H. Grummon, PhD, of the Harvard T. H. Chan School of Public Health, Boston, and Marissa G. Hall, PhD, of the University of North Carolina at Chapel Hill.

“Designing and adopting new alcohol warning labels should therefore be a research and policy priority,” they added.

The two researchers set out their arguments in a perspective article published in The New England Journal of Medicine.

“Alcohol consumption and its associated harms are reaching a crisis point in the United States,” they pointed out.

It now accounts for more than 140,000 deaths per year in the United States, according to the latest data from the Centers for Disease Control and Prevention. The COVID-19 pandemic has made the problem even worse – there was a 25% increase in alcohol-related deaths during 2020.

New, well-designed warning labels on alcohol is a common sense strategy for providing consumers with information and reducing the burden of alcohol-related harm, the authors suggested.
 

Warning Labels Prominently Displayed

Warning labels are most effective when they are prominently displayed, when they include pictures of some type, and when the messages alternate so as to avoid any one message from becoming “stale,” the authors noted. This approach has worked well with cigarette packs. This type of warning has increased smoking quit rates in comparison with smaller, side-of-pack, text-only warning labels.

There is some evidence that this type of labeling can be effective for alcohol. When large, pictorial warnings about cancer risk were temporarily added to the front of alcohol containers in some stores in Yukon, Canada, alcohol sales declined by 6%-10%, they pointed out.

However, pressure from the alcohol industry led to changes in the Yukon project, and while a general health warning remains, the label about increased cancer risk was removed.

The alcohol industry has tried to suppress efforts to educate the public, and this has created problems in conveying health information to consumers, the authors noted. The industry spends more than $1 billion each year to market its products in the United States.

The authors caution that without government intervention, the alcohol industry has little incentive to communicate the risks.

Some companies even link their products to health campaigns, such as selling pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast cancer research, despite compelling evidence linking alcohol to an increased risk of breast cancer.
 

Petition at Congress calling for new labels

This is not the first call for a change in the warning labels on alcohol.

Last year, a number of medical groups petitioned Congress for a new cancer-specific warning label to be displayed on all alcoholic beverages.

The petition was signed by the American Society of Clinical Oncology (ASCO), the American Institute for Cancer Research (AICR), and Breast Cancer Prevention Partners, in collaboration with the American Public Health Association, the Consumer Federation of America, the Center for Science in the Public Interest, Alcohol Justice, and the U.S. Alcohol Policy Alliance.

They are advocating for a label that would say: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

That petition is still pending, Melissa Maitin-Shepard, MPP, policy expert at the AICR, said in an interview.

In addition, the AICR is “working to advocate for the addition of a cancer warning label to alcoholic beverages through multiple channels,” she said. “Given the strong evidence linking alcohol use with at least six types of cancer – and low awareness of the alcohol and cancer connection – there is a tremendous need to educate the public about alcohol and cancer risk.”

Noelle K. LoConte, MD, associate professor of medicine at the University of Wisconsin, Madison, who is the lead author of ASCO’s statement on alcohol and cancer risk, emphasized that there is no doubt that alcohol is a carcinogen, that it causes about 5% of cancers globally, and that its use has increased during the pandemic.

“Initiatives that raise awareness around this issue could help generate more public support for policies that limit alcohol access and thereby decrease the number of alcohol-associated cancers,” she said. “In ASCO’s statement on alcohol and cancer, we recommend several key strategies to reduce high-risk alcohol consumption, including limiting youth access to alcohol, giving municipalities more control over alcohol outlet density and points of sale, and increasing taxes on alcohol.”

However, she also had a small criticism of one point in the NEJM article. It shows a sample infographic that lists gastric cancer as being caused by alcohol. “But as of today, gastric cancer is not on the IARC list of alcohol-associated cancers,” she said. “I think this brings to mind one critical point, that these warning labels have to contain scientifically established facts.”

Dr. Grummon and Dr. Hall have disclosed no relevant financial relationships.

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

Warning labels on alcoholic products need to be updated to spell out details of potential harm in order to make them more effective, two U.S. researchers have said.

The current labeling, which has not changed for 30 years, focuses on risks during pregnancy and with operating machinery and includes a vague statement that alcohol “may cause health problems.”

This is “so understated that it borders on being misleading,” the two researchers argued.

The science related to the use of alcohol has moved on, and there is now firm evidence of harm. Alcohol has been classified by the International Agency for Research on Cancer (IARC)  as a group 1 carcinogen and has been linked to an increased risk of many types of cancer. Drinking alcohol has also been linked to a wide range of other diseases, from liver disease to pancreatitis to some types of heart disease, the authors noted.

Yet the general public is mostly unaware of the most serious health risks that are associated with alcohol consumption, they pointed out.

“We believe Americans deserve the opportunity to make well-informed decisions about their alcohol consumption,” said Anna H. Grummon, PhD, of the Harvard T. H. Chan School of Public Health, Boston, and Marissa G. Hall, PhD, of the University of North Carolina at Chapel Hill.

“Designing and adopting new alcohol warning labels should therefore be a research and policy priority,” they added.

The two researchers set out their arguments in a perspective article published in The New England Journal of Medicine.

“Alcohol consumption and its associated harms are reaching a crisis point in the United States,” they pointed out.

It now accounts for more than 140,000 deaths per year in the United States, according to the latest data from the Centers for Disease Control and Prevention. The COVID-19 pandemic has made the problem even worse – there was a 25% increase in alcohol-related deaths during 2020.

New, well-designed warning labels on alcohol is a common sense strategy for providing consumers with information and reducing the burden of alcohol-related harm, the authors suggested.
 

Warning Labels Prominently Displayed

Warning labels are most effective when they are prominently displayed, when they include pictures of some type, and when the messages alternate so as to avoid any one message from becoming “stale,” the authors noted. This approach has worked well with cigarette packs. This type of warning has increased smoking quit rates in comparison with smaller, side-of-pack, text-only warning labels.

There is some evidence that this type of labeling can be effective for alcohol. When large, pictorial warnings about cancer risk were temporarily added to the front of alcohol containers in some stores in Yukon, Canada, alcohol sales declined by 6%-10%, they pointed out.

However, pressure from the alcohol industry led to changes in the Yukon project, and while a general health warning remains, the label about increased cancer risk was removed.

The alcohol industry has tried to suppress efforts to educate the public, and this has created problems in conveying health information to consumers, the authors noted. The industry spends more than $1 billion each year to market its products in the United States.

The authors caution that without government intervention, the alcohol industry has little incentive to communicate the risks.

Some companies even link their products to health campaigns, such as selling pink ribbon–themed alcoholic drinks during October to promote their efforts to raise funds for breast cancer research, despite compelling evidence linking alcohol to an increased risk of breast cancer.
 

Petition at Congress calling for new labels

This is not the first call for a change in the warning labels on alcohol.

Last year, a number of medical groups petitioned Congress for a new cancer-specific warning label to be displayed on all alcoholic beverages.

The petition was signed by the American Society of Clinical Oncology (ASCO), the American Institute for Cancer Research (AICR), and Breast Cancer Prevention Partners, in collaboration with the American Public Health Association, the Consumer Federation of America, the Center for Science in the Public Interest, Alcohol Justice, and the U.S. Alcohol Policy Alliance.

They are advocating for a label that would say: “WARNING: According to the Surgeon General, consumption of alcoholic beverages can cause cancer, including breast and colon cancers.”

That petition is still pending, Melissa Maitin-Shepard, MPP, policy expert at the AICR, said in an interview.

In addition, the AICR is “working to advocate for the addition of a cancer warning label to alcoholic beverages through multiple channels,” she said. “Given the strong evidence linking alcohol use with at least six types of cancer – and low awareness of the alcohol and cancer connection – there is a tremendous need to educate the public about alcohol and cancer risk.”

Noelle K. LoConte, MD, associate professor of medicine at the University of Wisconsin, Madison, who is the lead author of ASCO’s statement on alcohol and cancer risk, emphasized that there is no doubt that alcohol is a carcinogen, that it causes about 5% of cancers globally, and that its use has increased during the pandemic.

“Initiatives that raise awareness around this issue could help generate more public support for policies that limit alcohol access and thereby decrease the number of alcohol-associated cancers,” she said. “In ASCO’s statement on alcohol and cancer, we recommend several key strategies to reduce high-risk alcohol consumption, including limiting youth access to alcohol, giving municipalities more control over alcohol outlet density and points of sale, and increasing taxes on alcohol.”

However, she also had a small criticism of one point in the NEJM article. It shows a sample infographic that lists gastric cancer as being caused by alcohol. “But as of today, gastric cancer is not on the IARC list of alcohol-associated cancers,” she said. “I think this brings to mind one critical point, that these warning labels have to contain scientifically established facts.”

Dr. Grummon and Dr. Hall have disclosed no relevant financial relationships.

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

Individuals with type A blood have a 16% higher risk for early onset stroke (EOS) than those with other blood types, new research shows.

Conversely, results from a meta-analysis of nearly 17,000 cases of ischemic stroke in adults younger than 60 years showed that having type O blood reduced the risk for EOS by 12%.

In addition, the associations with risk were significantly stronger in EOS than in those with late-onset stroke (LOS), pointing to a stronger role for prothrombotic factors in younger patients, the researchers noted.

“What this is telling us is that maybe what makes you susceptible to stroke as a young adult is the blood type, which is really giving you a much higher risk of clotting and stroke compared to later onset,” coinvestigator Braxton Mitchell, PhD, professor of medicine and epidemiology and public health at the University of Maryland, Baltimore, said in an interview.

The findings were published online in Neurology.
 

Strong association

The genome-wide association study (GWAS) was done as part of the Genetics of Early Onset Ischemic Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. It assessed early onset ischemic stroke in patients aged 18-59 years.

Researchers included data from 16,927 patients with stroke. Of these, 5,825 had a stroke before age 60, defined as early onset. GWAS results were also examined for nearly 600,000 individuals without stroke.

Results showed two genetic variants tied to blood types A and O emerged as highly associated with risk for early stroke.

Researchers found that the protective effects of type O were significantly stronger with EOS vs. LOS (odds ratio [OR], 0.88 vs. 0.96, respectively; P = .001). Likewise, the association between type A and increased EOS risk was significantly stronger than that found in LOS (OR, 1.16 vs. 1.05; P = .005).

Using polygenic risk scores, the investigators also found that the greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared with LOS (P = .008).

Previous studies have shown a link between stroke risk and variants of the ABO gene, which determines blood type. The new analysis suggests that type A and O gene variants represent nearly all of those genetically linked with early stroke, the researchers noted.

While the findings point to blood type as a risk factor for stroke in younger people, Dr. Mitchell cautions that “at the moment, blood group does not have implications for preventive care.”

“The risk of stroke due to blood type is smaller than other risk factors that we know about, like smoking and hypertension,” he said. “I would be much more worried about these other risk factors, especially because those may be modifiable.”

He noted the next step in the study is to assess how blood type interacts with other known risk factors to raise stroke risk.

“There may be a subset of people where, if you have blood type A and you have some of these other risk factors, it’s possible that you may be at particularly high risk,” Dr. Mitchell said.
 

More research needed on younger patients

In an accompanying editorial, Jennifer Juhl Majersik, MD, associate professor of neurology at the University of Utah, Salt Lake City, and Paul Lacaze, PhD, associate professor and head of the public health genomics program at Monash University, Australia, noted that the study fills a gap in stroke research, which often focuses mostly on older individuals.

“In approximately 40% of people with EOS, the stroke is cryptogenic, and there is scant data from clinical trials to guide the selection of preventative strategies in this population, as people with EOS are often excluded from trials,” Dr. Majersik and Dr. Lacaze wrote.

“This work has deepened our understanding of EOS pathophysiology,” they added.

The editorialists noted that future research can build on the results from this analysis, “with the goal of a more precise understanding of stroke pathophysiology, leading to targeted preventative treatments for EOS and a reduction in disability in patients’ most productive years.”

Dr. Mitchell echoed the call for greater inclusion of young patients with stroke in clinical trials.

“As we’re learning, stroke in older folks isn’t the same as stroke in younger people,” he said. “There are many shared risk factors but there are also some that are different ... so there really is a need to include younger people.”

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

Individuals with type A blood have a 16% higher risk for early onset stroke (EOS) than those with other blood types, new research shows.

Conversely, results from a meta-analysis of nearly 17,000 cases of ischemic stroke in adults younger than 60 years showed that having type O blood reduced the risk for EOS by 12%.

In addition, the associations with risk were significantly stronger in EOS than in those with late-onset stroke (LOS), pointing to a stronger role for prothrombotic factors in younger patients, the researchers noted.

“What this is telling us is that maybe what makes you susceptible to stroke as a young adult is the blood type, which is really giving you a much higher risk of clotting and stroke compared to later onset,” coinvestigator Braxton Mitchell, PhD, professor of medicine and epidemiology and public health at the University of Maryland, Baltimore, said in an interview.

The findings were published online in Neurology.
 

Strong association

The genome-wide association study (GWAS) was done as part of the Genetics of Early Onset Ischemic Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. It assessed early onset ischemic stroke in patients aged 18-59 years.

Researchers included data from 16,927 patients with stroke. Of these, 5,825 had a stroke before age 60, defined as early onset. GWAS results were also examined for nearly 600,000 individuals without stroke.

Results showed two genetic variants tied to blood types A and O emerged as highly associated with risk for early stroke.

Researchers found that the protective effects of type O were significantly stronger with EOS vs. LOS (odds ratio [OR], 0.88 vs. 0.96, respectively; P = .001). Likewise, the association between type A and increased EOS risk was significantly stronger than that found in LOS (OR, 1.16 vs. 1.05; P = .005).

Using polygenic risk scores, the investigators also found that the greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared with LOS (P = .008).

Previous studies have shown a link between stroke risk and variants of the ABO gene, which determines blood type. The new analysis suggests that type A and O gene variants represent nearly all of those genetically linked with early stroke, the researchers noted.

While the findings point to blood type as a risk factor for stroke in younger people, Dr. Mitchell cautions that “at the moment, blood group does not have implications for preventive care.”

“The risk of stroke due to blood type is smaller than other risk factors that we know about, like smoking and hypertension,” he said. “I would be much more worried about these other risk factors, especially because those may be modifiable.”

He noted the next step in the study is to assess how blood type interacts with other known risk factors to raise stroke risk.

“There may be a subset of people where, if you have blood type A and you have some of these other risk factors, it’s possible that you may be at particularly high risk,” Dr. Mitchell said.
 

More research needed on younger patients

In an accompanying editorial, Jennifer Juhl Majersik, MD, associate professor of neurology at the University of Utah, Salt Lake City, and Paul Lacaze, PhD, associate professor and head of the public health genomics program at Monash University, Australia, noted that the study fills a gap in stroke research, which often focuses mostly on older individuals.

“In approximately 40% of people with EOS, the stroke is cryptogenic, and there is scant data from clinical trials to guide the selection of preventative strategies in this population, as people with EOS are often excluded from trials,” Dr. Majersik and Dr. Lacaze wrote.

“This work has deepened our understanding of EOS pathophysiology,” they added.

The editorialists noted that future research can build on the results from this analysis, “with the goal of a more precise understanding of stroke pathophysiology, leading to targeted preventative treatments for EOS and a reduction in disability in patients’ most productive years.”

Dr. Mitchell echoed the call for greater inclusion of young patients with stroke in clinical trials.

“As we’re learning, stroke in older folks isn’t the same as stroke in younger people,” he said. “There are many shared risk factors but there are also some that are different ... so there really is a need to include younger people.”

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

Individuals with type A blood have a 16% higher risk for early onset stroke (EOS) than those with other blood types, new research shows.

Conversely, results from a meta-analysis of nearly 17,000 cases of ischemic stroke in adults younger than 60 years showed that having type O blood reduced the risk for EOS by 12%.

In addition, the associations with risk were significantly stronger in EOS than in those with late-onset stroke (LOS), pointing to a stronger role for prothrombotic factors in younger patients, the researchers noted.

“What this is telling us is that maybe what makes you susceptible to stroke as a young adult is the blood type, which is really giving you a much higher risk of clotting and stroke compared to later onset,” coinvestigator Braxton Mitchell, PhD, professor of medicine and epidemiology and public health at the University of Maryland, Baltimore, said in an interview.

The findings were published online in Neurology.
 

Strong association

The genome-wide association study (GWAS) was done as part of the Genetics of Early Onset Ischemic Stroke Consortium, a collaboration of 48 different studies across North America, Europe, Japan, Pakistan, and Australia. It assessed early onset ischemic stroke in patients aged 18-59 years.

Researchers included data from 16,927 patients with stroke. Of these, 5,825 had a stroke before age 60, defined as early onset. GWAS results were also examined for nearly 600,000 individuals without stroke.

Results showed two genetic variants tied to blood types A and O emerged as highly associated with risk for early stroke.

Researchers found that the protective effects of type O were significantly stronger with EOS vs. LOS (odds ratio [OR], 0.88 vs. 0.96, respectively; P = .001). Likewise, the association between type A and increased EOS risk was significantly stronger than that found in LOS (OR, 1.16 vs. 1.05; P = .005).

Using polygenic risk scores, the investigators also found that the greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared with LOS (P = .008).

Previous studies have shown a link between stroke risk and variants of the ABO gene, which determines blood type. The new analysis suggests that type A and O gene variants represent nearly all of those genetically linked with early stroke, the researchers noted.

While the findings point to blood type as a risk factor for stroke in younger people, Dr. Mitchell cautions that “at the moment, blood group does not have implications for preventive care.”

“The risk of stroke due to blood type is smaller than other risk factors that we know about, like smoking and hypertension,” he said. “I would be much more worried about these other risk factors, especially because those may be modifiable.”

He noted the next step in the study is to assess how blood type interacts with other known risk factors to raise stroke risk.

“There may be a subset of people where, if you have blood type A and you have some of these other risk factors, it’s possible that you may be at particularly high risk,” Dr. Mitchell said.
 

More research needed on younger patients

In an accompanying editorial, Jennifer Juhl Majersik, MD, associate professor of neurology at the University of Utah, Salt Lake City, and Paul Lacaze, PhD, associate professor and head of the public health genomics program at Monash University, Australia, noted that the study fills a gap in stroke research, which often focuses mostly on older individuals.

“In approximately 40% of people with EOS, the stroke is cryptogenic, and there is scant data from clinical trials to guide the selection of preventative strategies in this population, as people with EOS are often excluded from trials,” Dr. Majersik and Dr. Lacaze wrote.

“This work has deepened our understanding of EOS pathophysiology,” they added.

The editorialists noted that future research can build on the results from this analysis, “with the goal of a more precise understanding of stroke pathophysiology, leading to targeted preventative treatments for EOS and a reduction in disability in patients’ most productive years.”

Dr. Mitchell echoed the call for greater inclusion of young patients with stroke in clinical trials.

“As we’re learning, stroke in older folks isn’t the same as stroke in younger people,” he said. “There are many shared risk factors but there are also some that are different ... so there really is a need to include younger people.”

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

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

New research links the use of glucocorticoids with changes in white matter microstructure – which may explain the development of anxiety, depression, and other neuropsychiatric side effects related to these drugs, investigators say.

Results from a cross-sectional study showed that use of both systemic and inhaled glucocorticoids was associated with widespread reductions in fractional anisotropy (FA) and increases in mean diffusivity.

Glucocorticoids have “a whole catalogue” of adverse events, and effects on brain structure “adds to the list,” co-investigator Onno C. Meijer, PhD, professor of molecular neuroendocrinology of corticosteroids, department of medicine, Leiden University Medical Center, the Netherlands, told this news organization.

Serious side effects

Glucocorticoids, a class of synthetic steroids with immunosuppressive properties, are prescribed for a wide range of conditions, including rheumatoid arthritis and asthma.

However, they are also associated with potentially serious metabolic, cardiovascular, and musculoskeletal side effects as well as neuropsychiatric side effects such as depression, mania, and cognitive impairment.

About 1 in 3 patients exposed to “quite a lot of these drugs” will experience neuropsychiatric symptoms, Dr. Meijer said.

Most previous studies that investigated effects from high levels of glucocorticoids on brain structure have been small and involved selected populations, such as those with Cushing disease.

The new study included participants from the UK Biobank, a large population-based cohort. Participants had undergone imaging and did not have a history of psychiatric disease – although they could have conditions associated with glucocorticoid use, including anxiety, depression, mania, or delirium.

The analysis included 222 patients using oral or parenteral glucocorticoids at the time of imaging (systemic group), 557 using inhaled glucocorticoids, and 24,106 not using glucocorticoids (the control group).

Inhaled steroids target the lungs, whereas a steroid in pill form “travels in the blood and reaches each and every organ and cell in the body and typically requires higher doses,” Dr. Meijer noted.

The groups were similar with respect to sex, education, and smoking status. However, the systemic glucocorticoid group was slightly older (mean age, 66.1 years vs. 63.3 years for inhaled glucocorticoid users and 63.5 years for the control group).

In addition to age, researchers adjusted for sex, education level, head position in the scanner, head size, assessment center, and year of imaging.
 

Imaging analyses

Imaging analyses showed systemic glucocorticoid use was associated with reduced global FA (adjusted mean difference, -3.7e-3; 95% confidence interval, -6.4e-3 to 1.0e-3), and reductions in regional FA in the body and genu of the corpus callosum versus the control group.

Inhaled glucocorticoid use was associated with reduced global FA (AMD, -2.3e-3; 95% CI, -4.0e-3 to -5.7e-4), and lower FA in the splenium of the corpus callosum and the cingulum of the hippocampus.

Global mean diffusivity was higher in systemic glucocorticoid users (AMD, 7.2e-6; 95% CI, 3.2e-6 to 1.1e-5) and inhaled glucocorticoid users (AMD, 2.7e-6; 95% CI, 1.7e-7 to 5.2e-6), compared with the control group.

The effects of glucocorticoids on white matter were “pervasive,” and the “most important finding” of the study, Dr. Meijer said. “We were impressed by the fact white matter is so sensitive to these drugs.”

He noted that it is likely that functional connectivity between brain regions is affected by use of glucocorticoids. “You could say communication between brain regions is probably somewhat impaired or challenged,” he said.

Subgroup analyses among participants using glucocorticoids chronically, defined as reported at two consecutive visits, suggested a potential dose-dependent or duration-dependent effect of glucocorticoids on white matter microstructure.

Systemic glucocorticoid use was also associated with an increase in total and grey matter volume of the caudate nucleus.

In addition, there was a significant association between inhaled glucocorticoid use and decreased grey matter volume of the amygdala, which Dr. Meijer said was surprising because studies have shown that glucocorticoids “can drive amygdala big time.”
 

Move away from ‘one dose for all’?

Another surprise was that the results showed no hippocampal volume differences with steroid use, Dr. Meijer noted.

The modest association between glucocorticoid use and brain volumes could indicate that white matter integrity is more sensitive to glucocorticoids than is grey matter volume, “at least at the structural level,” he said.

He added that longer use or higher doses may be necessary to also induce volumetric changes.

Participants also completed a questionnaire to assess mood over the previous 2 weeks. Systemic glucocorticoid users had more depressive symptoms, disinterest, tenseness/restlessness, and tiredness/lethargy, compared with the control group. Inhaled glucocorticoid users only reported more tiredness/lethargy.

The investigators note that mood-related effects could be linked to the condition for which glucocorticoids were prescribed: for example, rheumatoid arthritis or chronic obstructive pulmonary disease.

In terms of cognition, systemic glucocorticoid users performed significantly worse on the symbol digit substitution task, compared with participants in the control group.

In light of these findings, pharmaceutical companies that make inhaled corticosteroids “should perhaps find out if glucocorticoids can be dosed by kilogram body weight rather than simply one dose fits all,” which is currently the case, Dr. Meijer said.
 

Impressive, but several limitations

Commenting on the findings, E. Sherwood Brown, MD, PhD, Distinguished Chair in Psychiatric Research and professor and vice chair for clinical research, department of psychiatry, The University of Texas Southwestern Medical Center, Dallas, called the study sample size “impressive.”

In addition, the study is the first to look at systemic as well as inhaled corticosteroids, said Dr. Brown, who was not involved with the research. He noted that previously, there had been only case reports of psychiatric symptoms with inhaled corticosteroids.

That results are in the same direction but greater with systemic, compared with inhaled corticosteroids, is “particularly interesting” because this might suggest dose-dependent effects, Dr. Brown said.

He noted that cognitive differences were also only observed with systemic corticosteroids.

Some study observations, such as smaller amygdala volume with inhaled but not systemic corticosteroids, “are harder to understand,” said Dr. Brown.

However, he pointed out some study limitations. For example, data were apparently unavailable for verbal and declarative memory test data, despite corticosteroids probably affecting the hippocampus and causing memory changes.

Other drawbacks were that the dose and duration of corticosteroid use, as well as the medical histories of study participants, were not available, Dr. Brown said.

No study funding was reported. Dr. Meijer has received research grants and honorariums from Corcept Therapeutics and a speakers’ fee from Ipsen. Dr. Brown is on an advisory board for Sage Pharmaceuticals, which is developing neurosteroids (not corticosteroids) for mood disorders. He is also on a Medscape advisory board related to bipolar disorder.

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

Intera Oncology has recalled 440 Intera 3000 Hepatic Artery Infusion Pumps following three reports of potentially life-threatening medication flow rates.

Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.

Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.

The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.

The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.

Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.

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

Intera Oncology has recalled 440 Intera 3000 Hepatic Artery Infusion Pumps following three reports of potentially life-threatening medication flow rates.

Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.

Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.

The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.

The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.

Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.

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

Intera Oncology has recalled 440 Intera 3000 Hepatic Artery Infusion Pumps following three reports of potentially life-threatening medication flow rates.

Although no injuries or deaths related to the pump malfunction have been reported yet, the U.S. Food and Drug Administration has deemed the recall Class I, the most serious category that indicates the device could cause injury or death.

Intera Oncology initiated the recall in July following reports from clinicians that the pumps, which are implanted to deliver chemotherapy to treat liver tumors, were delivering medications faster than expected. A fast flow rate can lead to life-threatening hematologic toxicity, neurotoxicity, or death. It also means patients will run out of medication too soon, potentially leading to disease progression or death.

The FDA notice states the company has advised customers to continue to monitor flow rate as per standard refill procedure as well as monitor for liver toxicity to adjust dosing as per standard protocols.

The company also said to consider pump replacement if altered flow can’t be adequately managed by dosing adjustments or having patients come in for medication refills and to verify the flow rate sooner than every 2 weeks if the pump appears to be flowing more than 15% outside its labeled specification.

Questions about the recall can be directed to Intera Oncology at (800) 660-2660 or support@interaoncol.

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

Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).

“The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control,” wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.

Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).

“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.

The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.

In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.

“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
 

Four-way trial

To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.

The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.

Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.

There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.

Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).

The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.

Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).

“The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control,” wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.

Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).

“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.

The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.

In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.

“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
 

Four-way trial

To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.

The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.

Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.

There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.

Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).

The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.

Giving a boost radiation dose to the tumor bed following breast-conserving surgery and whole breast irradiation (WBI) has been shown to be effective at reducing recurrence of invasive breast cancer, and now a multinational randomized trial has shown that it can do the same for patients with non–low-risk ductal carcinoma in situ (DCIS).

“The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control,” wrote the authors, led by Boon H. Chua, PhD, from the University of New South Wales, Sydney.

Among 1,608 patients with DCIS with at least one clinical or pathological marker for increased risk of local recurrence, 5-year rates of freedom from local recurrence were 97.1% for patients assigned to received a tumor bed boost versus 92.7% for patients who did not receive a boost dose. This difference translated into a hazard ratio for recurrence with radiation boost of 0.47 (P < .001).

“Our results support the use of tumor-bed boost radiation after postoperative WBI in patients with non–low-risk DCIS to optimize local control, and the adoption of moderately hypofractionated whole breast irradiation in practice to improve the balance of local control, toxicity, and socioeconomic burdens of treatment,” the authors wrote in a study published in The Lancet.

The investigators, from cancer centers in Australia, Europe, and Canada, noted that the advent of screening mammography was followed by a substantial increase in the diagnosis of DCIS. They also noted that patients who undergo breast-conserving surgery for DCIS are at risk for local recurrence, and half of recurrences present as invasive disease.

In addition, they said, there were high recurrence rates in randomized clinical for patients with DCIS who received conventionally fractionated WBI without a tumor boost following surgery.

“Further, the inconvenience of a 5- to 6-week course of conventionally fractionated WBI decreased the quality of life of patients. Thus, tailoring radiation dose fractionation according to recurrence risk is a prominent controversy in the radiation treatment of DCIS,” they wrote.
 

Four-way trial

To see whether a tumor-bed boost following WBI and alternative WBI fractionation schedules could improve outcomes for patients with non–low-risk DCIS, the researchers enrolled patients and assigned them on an equal basis to one of four groups, in which they would receive either conventional or hypofractionated WBI with or without a tumor-bed boost.

The conventional WBI regimen consisted of a total of 50 Gy delivered over 25 fractions. The hypofractionated regimen consisted of a total dose of 42.5 Gy delivered in 16 fractions. Patients assigned to get a boost dose to the tumor bed received an additional 16 Gy in eight fractions after WBI.

Of the 1,608 patients enrolled who eligible for randomization, 803 received a boost dose and 805 did not. As noted before, the risk of recurrence at 5 years was significantly lower with boosting, with 5-year free-from-local-recurrence rates of 97.1%, compared with 92.7% for patients who did not get a tumor-bed boost.

There were no significant differences according to fractionation schedule, however: among all randomly assigned patients the rate of 5-year freedom from recurrence was 94.9% for both the conventionally fractionated and hypofractionated WBI groups.

Not surprisingly, patients who received the boost dose had higher rates of grade 2 or greater toxicities, including breast pain (14% vs. 10%; P = .03) and induration (14% vs. 6%; P < .001).

The study was supported by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. Dr. Chua disclosed grant support from the organizations and others.

Endoscopic ultrasound (EUS)–guided through-the-needle biopsies (TTNBs) of pancreatic cystic lesions are sufficient for accurate molecular analysis, which offers a superior alternative to cyst fluid obtained via fine-needle aspiration, based on a prospective study.

For highest diagnostic clarity, next-generation sequencing (NGS) of TTNBs can be paired with histology, lead author Charlotte Vestrup Rift, MD, PhD, of Copenhagen University Hospital, and colleagues reported.

“The diagnostic algorithm for the management of [pancreatic cystic lesions] includes endoscopic ultrasound examination with aspiration of cyst fluid for cytology,” the investigators wrote in Gastrointestinal Endoscopy. “However, the reported sensitivity of cytology is low [at 54%]. A new microforceps, introduced through a 19-gauge needle, has proven useful for procurement of [TTNBs] that represent both the epithelial and stromal component of the cyst wall. TTNBs have a high sensitivity of 86% for the diagnosis of mucinous cysts.”

Dr. Rift and colleagues evaluated the impact of introducing NGS to the diagnostic process. They noted that concomitant mutations in GNAS and KRAS are diagnostic for intraductal papillary mucinous neoplasms (IPMNs), while other mutations have been linked with progression to cancer.

The study involved 101 patients with pancreatic cystic lesions larger than 15 mm in diameter, mean age of 68 years, among whom 91 had residual TTNBs available after microscopic analysis. These samples underwent a 51-gene NGS panel that included the “most prevalent hot-spot mutations.” Diagnoses were sorted into four categories: neoplastic cyst, mucinous cyst, IPMN, or serous cystic neoplasm.

The primary endpoint was diagnostic yield, both for molecular analysis of TTNBs and for molecular analysis plus histopathology of TTNBs. Sensitivity and specificity of NGS were also determined using histopathology as the gold standard.

Relying on NGS alone, diagnostic yields were 44.5% and 27.7% for detecting a mucinous cyst and determining type of cyst, respectively. These yields rose to 73.3% and 70.3%, respectively, when NGS was used with microscopic evaluation. Continuing with this combined approach, sensitivity and specificity were 83.7% and 81.8%, respectively, for the diagnosis of a mucinous cyst. Sensitivity and specificity were higher still, at 87.2% and 84.6%, respectively, for identifying IPMNs.

The adverse-event rate was 9.9%, with a risk of postprocedure acute pancreatitis of 8.9 % and procedure-associated intracystic bleeding of 3%, according to the authors.

Limitations of the study include the relatively small sample size and the single-center design.

“TTNB-NGS is not sufficient as a stand-alone diagnostic tool as of yet but has a high diagnostic yield when combined with microscopic evaluation and subtyping by immunohistochemistry,” the investigators concluded. “The advantage of EUS-TTNB over EUS–[fine-needle aspiration] is the ability to perform detailed cyst subtyping and the high technical success rate of the procedure. ... However, the procedure comes with a risk of adverse events and thus should be offered to patients where the value of an exact diagnosis outweighs the risks.”

“Molecular subtyping is emerging as a useful clinical test for diagnosing pancreatic cysts,” said Margaret Geraldine Keane, MBBS, MSc, of Johns Hopkins Medicine, Baltimore, although she noted that NGS remains expensive and sporadically available, “which limits its clinical utility and incorporation into diagnostic algorithms for pancreatic cysts. In the future, as the cost of sequencing reduces, and availability improves, this may change.”

For now, Dr. Keane advised physicians to reserve molecular subtyping for cases in which “accurate cyst subtyping will change management ... or when other tests have not provided a clear diagnosis.”

She said the present study is valuable because better diagnostic tests are badly needed for patients with pancreatic cysts, considering the high rate of surgical overtreatment.

“Having more diagnostic tests, such as those described in this publication [to be used on their own or in combination] to decide which patients need surgery, is important,” Dr. Keane said who was not involved in the study.

Better diagnostic tests could also improve outcomes for patients with pancreatic cancer, she said, noting a 5-year survival rate of 10%.

“This outcome is in large part attributable to the late stage at which the majority of patients are diagnosed,” Dr. Keane said. “If patients can be diagnosed earlier, survival dramatically improves. Improvements in diagnostic tests for premalignant pancreatic cystic lesions are therefore vital.”

The study was supported by Rigshospitalets Research Foundation, The Novo Nordisk Foundation, The Danish Cancer Society, and others, although they did not have a role in conducting the study or preparing the manuscript. One investigator disclosed a relationship with MediGlobe. The other investigators reported no conflicts of interest. Dr. Keane disclosed no conflicts of interest.

Endoscopic ultrasound (EUS)–guided through-the-needle biopsies (TTNBs) of pancreatic cystic lesions are sufficient for accurate molecular analysis, which offers a superior alternative to cyst fluid obtained via fine-needle aspiration, based on a prospective study.

For highest diagnostic clarity, next-generation sequencing (NGS) of TTNBs can be paired with histology, lead author Charlotte Vestrup Rift, MD, PhD, of Copenhagen University Hospital, and colleagues reported.

“The diagnostic algorithm for the management of [pancreatic cystic lesions] includes endoscopic ultrasound examination with aspiration of cyst fluid for cytology,” the investigators wrote in Gastrointestinal Endoscopy. “However, the reported sensitivity of cytology is low [at 54%]. A new microforceps, introduced through a 19-gauge needle, has proven useful for procurement of [TTNBs] that represent both the epithelial and stromal component of the cyst wall. TTNBs have a high sensitivity of 86% for the diagnosis of mucinous cysts.”

Dr. Rift and colleagues evaluated the impact of introducing NGS to the diagnostic process. They noted that concomitant mutations in GNAS and KRAS are diagnostic for intraductal papillary mucinous neoplasms (IPMNs), while other mutations have been linked with progression to cancer.

The study involved 101 patients with pancreatic cystic lesions larger than 15 mm in diameter, mean age of 68 years, among whom 91 had residual TTNBs available after microscopic analysis. These samples underwent a 51-gene NGS panel that included the “most prevalent hot-spot mutations.” Diagnoses were sorted into four categories: neoplastic cyst, mucinous cyst, IPMN, or serous cystic neoplasm.

The primary endpoint was diagnostic yield, both for molecular analysis of TTNBs and for molecular analysis plus histopathology of TTNBs. Sensitivity and specificity of NGS were also determined using histopathology as the gold standard.

Relying on NGS alone, diagnostic yields were 44.5% and 27.7% for detecting a mucinous cyst and determining type of cyst, respectively. These yields rose to 73.3% and 70.3%, respectively, when NGS was used with microscopic evaluation. Continuing with this combined approach, sensitivity and specificity were 83.7% and 81.8%, respectively, for the diagnosis of a mucinous cyst. Sensitivity and specificity were higher still, at 87.2% and 84.6%, respectively, for identifying IPMNs.

The adverse-event rate was 9.9%, with a risk of postprocedure acute pancreatitis of 8.9 % and procedure-associated intracystic bleeding of 3%, according to the authors.

Limitations of the study include the relatively small sample size and the single-center design.

“TTNB-NGS is not sufficient as a stand-alone diagnostic tool as of yet but has a high diagnostic yield when combined with microscopic evaluation and subtyping by immunohistochemistry,” the investigators concluded. “The advantage of EUS-TTNB over EUS–[fine-needle aspiration] is the ability to perform detailed cyst subtyping and the high technical success rate of the procedure. ... However, the procedure comes with a risk of adverse events and thus should be offered to patients where the value of an exact diagnosis outweighs the risks.”

“Molecular subtyping is emerging as a useful clinical test for diagnosing pancreatic cysts,” said Margaret Geraldine Keane, MBBS, MSc, of Johns Hopkins Medicine, Baltimore, although she noted that NGS remains expensive and sporadically available, “which limits its clinical utility and incorporation into diagnostic algorithms for pancreatic cysts. In the future, as the cost of sequencing reduces, and availability improves, this may change.”

For now, Dr. Keane advised physicians to reserve molecular subtyping for cases in which “accurate cyst subtyping will change management ... or when other tests have not provided a clear diagnosis.”

She said the present study is valuable because better diagnostic tests are badly needed for patients with pancreatic cysts, considering the high rate of surgical overtreatment.

“Having more diagnostic tests, such as those described in this publication [to be used on their own or in combination] to decide which patients need surgery, is important,” Dr. Keane said who was not involved in the study.

Better diagnostic tests could also improve outcomes for patients with pancreatic cancer, she said, noting a 5-year survival rate of 10%.

“This outcome is in large part attributable to the late stage at which the majority of patients are diagnosed,” Dr. Keane said. “If patients can be diagnosed earlier, survival dramatically improves. Improvements in diagnostic tests for premalignant pancreatic cystic lesions are therefore vital.”

The study was supported by Rigshospitalets Research Foundation, The Novo Nordisk Foundation, The Danish Cancer Society, and others, although they did not have a role in conducting the study or preparing the manuscript. One investigator disclosed a relationship with MediGlobe. The other investigators reported no conflicts of interest. Dr. Keane disclosed no conflicts of interest.

Endoscopic ultrasound (EUS)–guided through-the-needle biopsies (TTNBs) of pancreatic cystic lesions are sufficient for accurate molecular analysis, which offers a superior alternative to cyst fluid obtained via fine-needle aspiration, based on a prospective study.

For highest diagnostic clarity, next-generation sequencing (NGS) of TTNBs can be paired with histology, lead author Charlotte Vestrup Rift, MD, PhD, of Copenhagen University Hospital, and colleagues reported.

“The diagnostic algorithm for the management of [pancreatic cystic lesions] includes endoscopic ultrasound examination with aspiration of cyst fluid for cytology,” the investigators wrote in Gastrointestinal Endoscopy. “However, the reported sensitivity of cytology is low [at 54%]. A new microforceps, introduced through a 19-gauge needle, has proven useful for procurement of [TTNBs] that represent both the epithelial and stromal component of the cyst wall. TTNBs have a high sensitivity of 86% for the diagnosis of mucinous cysts.”

Dr. Rift and colleagues evaluated the impact of introducing NGS to the diagnostic process. They noted that concomitant mutations in GNAS and KRAS are diagnostic for intraductal papillary mucinous neoplasms (IPMNs), while other mutations have been linked with progression to cancer.

The study involved 101 patients with pancreatic cystic lesions larger than 15 mm in diameter, mean age of 68 years, among whom 91 had residual TTNBs available after microscopic analysis. These samples underwent a 51-gene NGS panel that included the “most prevalent hot-spot mutations.” Diagnoses were sorted into four categories: neoplastic cyst, mucinous cyst, IPMN, or serous cystic neoplasm.

The primary endpoint was diagnostic yield, both for molecular analysis of TTNBs and for molecular analysis plus histopathology of TTNBs. Sensitivity and specificity of NGS were also determined using histopathology as the gold standard.

Relying on NGS alone, diagnostic yields were 44.5% and 27.7% for detecting a mucinous cyst and determining type of cyst, respectively. These yields rose to 73.3% and 70.3%, respectively, when NGS was used with microscopic evaluation. Continuing with this combined approach, sensitivity and specificity were 83.7% and 81.8%, respectively, for the diagnosis of a mucinous cyst. Sensitivity and specificity were higher still, at 87.2% and 84.6%, respectively, for identifying IPMNs.

The adverse-event rate was 9.9%, with a risk of postprocedure acute pancreatitis of 8.9 % and procedure-associated intracystic bleeding of 3%, according to the authors.

Limitations of the study include the relatively small sample size and the single-center design.

“TTNB-NGS is not sufficient as a stand-alone diagnostic tool as of yet but has a high diagnostic yield when combined with microscopic evaluation and subtyping by immunohistochemistry,” the investigators concluded. “The advantage of EUS-TTNB over EUS–[fine-needle aspiration] is the ability to perform detailed cyst subtyping and the high technical success rate of the procedure. ... However, the procedure comes with a risk of adverse events and thus should be offered to patients where the value of an exact diagnosis outweighs the risks.”

“Molecular subtyping is emerging as a useful clinical test for diagnosing pancreatic cysts,” said Margaret Geraldine Keane, MBBS, MSc, of Johns Hopkins Medicine, Baltimore, although she noted that NGS remains expensive and sporadically available, “which limits its clinical utility and incorporation into diagnostic algorithms for pancreatic cysts. In the future, as the cost of sequencing reduces, and availability improves, this may change.”

For now, Dr. Keane advised physicians to reserve molecular subtyping for cases in which “accurate cyst subtyping will change management ... or when other tests have not provided a clear diagnosis.”

She said the present study is valuable because better diagnostic tests are badly needed for patients with pancreatic cysts, considering the high rate of surgical overtreatment.

“Having more diagnostic tests, such as those described in this publication [to be used on their own or in combination] to decide which patients need surgery, is important,” Dr. Keane said who was not involved in the study.

Better diagnostic tests could also improve outcomes for patients with pancreatic cancer, she said, noting a 5-year survival rate of 10%.

“This outcome is in large part attributable to the late stage at which the majority of patients are diagnosed,” Dr. Keane said. “If patients can be diagnosed earlier, survival dramatically improves. Improvements in diagnostic tests for premalignant pancreatic cystic lesions are therefore vital.”

The study was supported by Rigshospitalets Research Foundation, The Novo Nordisk Foundation, The Danish Cancer Society, and others, although they did not have a role in conducting the study or preparing the manuscript. One investigator disclosed a relationship with MediGlobe. The other investigators reported no conflicts of interest. Dr. Keane disclosed no conflicts of interest.