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Sugary drinks may up risk for liver cancer, liver disease death
The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.
“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.
When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”
The new study was published online in JAMA.
About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.
Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.
In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”
To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.
Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.
Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.
Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).
Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).
The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.
Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.
“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.
The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”
Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”
In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.
“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.
However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”
It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”
Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”
In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.
In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”
“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”
The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.
A version of this article appeared on Medscape.com.
The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.
“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.
When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”
The new study was published online in JAMA.
About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.
Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.
In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”
To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.
Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.
Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.
Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).
Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).
The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.
Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.
“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.
The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”
Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”
In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.
“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.
However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”
It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”
Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”
In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.
In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”
“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”
The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.
A version of this article appeared on Medscape.com.
The observational analyses revealed that postmenopausal women who consumed at least one sugar-sweetened beverage daily had an 85% higher risk of developing liver cancer and a 68% higher risk of dying from chronic liver disease, compared with those who consumed three servings or fewer per month.
“If our findings are confirmed, reducing sugar-sweetened beverage consumption might serve as a public health strategy to reduce liver disease burden,” first author Longgang Zhao, PhD, with Brigham and Women’s Hospital and Harvard Medical School, both in Boston, said in an interview.
When looking at consumption of artificially sweetened drinks, however, Dr. Zhao and colleagues found no strong association between intake and risk for liver cancer or death from chronic liver disease. Because the sample size for the artificially sweetened beverage analysis was limited, Dr. Zhao said, “these results should be interpreted with caution and additional studies are needed to confirm our study findings.”
The new study was published online in JAMA.
About 40% of people with liver cancer do not have one of the well-known disease risk factors, such as chronic hepatitis B or C infection, type 2 diabetes, or obesity. In the current analysis, Dr. Zhao and colleagues wanted to determine whether sugar-sweetened or artificially sweetened beverages, consumed by a large swath of the population, could be a risk factor for liver cancer or chronic liver disease.
Two previous studies have found only a “potential association” between sugar-sweetened beverage intake and a person’s risk for liver cancer, the authors explained.
In July, the International Agency for Research on Cancer officially classified the artificial sweetener aspartame as a possible carcinogen, but cancer epidemiologist Paul Pharoah, MD, PhD, commented that “the evidence that aspartame causes primary liver cancer, or any other cancer in humans, is very weak.”
To provide greater clarity about a potential link, the study team used the Women’s Health Initiative to evaluate sugary beverage consumption among 98,786 postmenopausal women and artificially sweetened drink intake among 64,787 followed for up to a median of 20.9 years. The primary outcomes were liver cancer incidence and mortality from chronic liver disease, defined as nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis.
Among these women, nearly 7% consumed at least one sugar-sweetened beverage daily and 13% consumed one or more artificially sweetened beverage servings daily.
Over the follow-up period, 207 women developed liver cancer and 148 died from chronic liver disease in the sugary beverage group while 133 women developed liver cancer and 74 died from chronic liver disease in the artificial sugar group.
Compared with women consuming three servings or fewer of sugar-sweetened beverages per month, those consuming one or more servings per day had a significantly higher risk for liver cancer (18.0 vs. 10.3 per 100,000; adjusted hazard ratio, 1.85; P = .01) and for chronic liver disease mortality (17.7 vs. 7.1 per 100,000; aHR, 1.68; P = .04).
Compared with women consuming three servings or fewer of artificially sweetened beverages per month, those drinking one or more servings per day did not have a significantly increased risk for liver cancer (11.8 vs. 10.2 per 100,000; aHR, 1.17; P = .55) or chronic liver disease mortality (7.1 vs. 5.3 per 100,000; aHR 0.95; P = .88).
The authors noted several limitations to the study, including not tracking potential changes in beverage consumption over time or details on the specific sugar content or sweetener types consumed.
Corresponding author Xuehong Zhang, ScD, also with Brigham and Women’s Hospital and Harvard Medical School, said it’s not surprising that sugar-sweetened beverages may raise the risk of adverse liver outcomes.
“Intake of sugar-sweetened beverage[s], a postulated risk factor for obesity, diabetes, and cardiovascular disease, may drive insulin resistance and inflammation, which are strongly implicated in liver carcinogenesis and liver health,” Dr. Zhang said in an interview.
The lack of an association between artificially sweetened beverages and liver outcomes is also not particularly surprising, Dr. Zhang said, “given that the consumption level of artificially sweetened beverages is low, the sample size is relatively small,” and “the dose response relationship remains unknown.”
Nancy S. Reau, MD, who was not involved in the research, said the authors should be “congratulated for trying to clarify liver-related health risk related to artificial or sugar-sweetened beverages.”
In her view, the most important finding is the association between daily consumption of sugar-sweetened beverages and liver health.
“Regardless of whether this is a surrogate marker for liver disease risk (such as fatty liver disease) or a consequence of the drink itself, it is an easy measure for clinicians to capture and an easy behavior for patients to modify,” Dr. Reau, a hepatologist at Rush Medical College, Chicago, said in an interview.
However, Dr. Reau noted, “I do not feel that this article can be used to advocate for artificially sweetened beverages as a substitute.”
It is possible, she explained, that this population was too small to see a significant signal between artificially sweetened beverages and liver health. Plus, “natural, low-caloric beverages as part of a healthy diet combined with exercise are always going to be ideal.”
Weighing in as well, Dale Shepard, MD, PhD, a medical oncologist at the Cleveland Clinic, noted that “this is another study that points to the need for moderation.”
In his view, avoiding excess consumption of sugary or artificially sweetened drinks is the best course of action, but other factors, such as smoking, excessive alcohol, sun exposure without adequate sunscreen, obesity, and inactivity “are more likely to increase one’s risk for cancer,” Dr. Shepard said.
In a statement from the U.K.-based Science Media Centre, Pauline Emmett, PhD, from the University of Bristol (England), commented that this is a “good-quality” study and “the authors have been very careful not to speculate.”
“The main limitation is that this is observational data which provides associations which suggest a relationship but cannot tell if it is causal,” Dr. Emmett said. However, “we know from a body of evidence that it is worth thinking twice before choosing to drink sugar-sweetened beverages every day.”
The study had no commercial funding. Dr. Zhao, Dr. Zhang, Dr. Reau, and Dr. Shepard reported no relevant financial relationships. Dr. Emmett is a member of the European Food Safety Authority working group on dietary sugars.
A version of this article appeared on Medscape.com.
FROM JAMA
Ontario case shows potential supplement risk for consumers
A woman’s quest to become pregnant resulted in lead poisoning from an Ayurvedic treatment. The case triggered the seizure of pills from an Ontario natural-products clinic and the issuance of government warnings about the risks of products from this business, according to a new report.
, including the presence of lead and other metals in Ayurvedic products, according to the report.
“When consumer products may be contaminated with lead, or when lead exposure is linked to sources in the community, involving public health can facilitate broader actions to reduce and prevent exposures to other people at risk,” wrote report author Julian Gitelman, MD, MPH, a resident physician at the University of Toronto Dalla Lana School of Public Health, and colleagues.
Their case study was published in the Canadian Medical Association Journal.
The researchers detailed what happened after a 39-year-old woman sought medical care for abdominal pain, constipation, nausea, and vomiting. The woman underwent a series of tests, including colonoscopy, laparoscopy, and biopsies of bone marrow and ovarian cysts.
Only later did clinicians home in on the cause of her ailments: the Ayurvedic medications that the patient had been taking daily for more than a year for infertility. Her daily regimen had varied, ranging from a few pills to a dozen pills.
Heavy metals are sometimes intentionally added to Ayurvedic supplements for perceived healing properties, wrote the authors. They cited a previous study of a sample of Ayurvedic pills bought on the Internet from manufacturers based in the United States and India that showed that 21% contained lead, mercury, or arsenic.
A case report published last year in German Medical Weekly raised the same issue.
Melatonin gummies
Regulators in many countries struggle to help consumers understand the risks of natural health supplements, and the challenge extends well beyond Ayurvedic products.
There has been a “huge and very troubling increase” in U.S. poison control calls associated with gummy-bear products containing melatonin, said Canadian Senator Stan Kutcher, MD, at a May 11 meeting of Canada’s Standing Senate Committee on Social Affairs, Science, and Technology.
In April, JAMA published a U.S. analysis of melatonin gummy products, Dr. Kutcher noted. In this research letter, investigators reported that one product did not contain detectable levels of melatonin but did contain 31.3 mg of cannabidiol.
In other products, the quantity of melatonin ranged from 74% to 347% of the labeled quantity. A previous Canadian study of 16 melatonin brands found that the actual dose of melatonin ranged from 17% to 478% of the declared quantity, the letter noted.
The May 11 Senate meeting provided a forum for many of the recurring debates about supplements, which also are known as natural health products.
Barry Power, PharmD, editor in chief for the Canadian Pharmacists Association, said that his group was disappointed when Canada excluded natural health products from Vanessa’s Law, which was passed in 2014. This law sought to improve the reporting of adverse reactions to drugs.
“We’re glad this is being revisited now,” Dr. Power told the Senate committee. “Although natural health products are often seen as low risk, we need to keep in mind that ‘low risk’ does not mean ‘no risk,’ and ‘natural’ does not mean ‘safe.’ ”
In contrast, Aaron Skelton, chief executive of the Canadian Health Food Association, spoke against this bid to expand the reach of Vanessa’s Law into natural health products. Canadian lawmakers attached provisions regarding increased oversight of natural health products to a budget package instead of considering them as part of a stand-alone bill.
“Our concern is that the powers that are being discussed have not been reviewed and debated,” Mr. Skelton told Dr. Kutcher. “The potential for overreach and unnecessary regulation is significant, and that deserves debate.”
“Profits should not trump Canadians’ health,” answered Dr. Kutcher, who earlier served as head of the psychiatry department at Dalhousie University in Halifax, N.S.
By June, Vanessa’s Law had been expanded with provisions that address natural health products, including the reporting of products that present a serious risk to consumers.
Educating consumers
Many consumers overestimate the level of government regulation of supplements, said Pieter A. Cohen, MD, leader of the Supplement Research Program at Cambridge Health Alliance in Massachusetts. Dr. Cohen was the lead author of the JAMA research letter about melatonin products.
Supplements often share shelves in pharmacies with medicines that are subject to more strict regulation, which causes confusion.
“It’s really hard to wrap your brain around [the fact] that a health product is being sold in pharmacies in the United States and it’s not being vetted by the FDA [U.S. Food and Drug Administration]”, Dr. Cohen said in an interview
The confusion extends across borders. Many consumers in other countries will assume that the FDA performed premarket screening of U.S.-made supplements, but that is not the case, he said.
People who want to take supplements should look for reputable sources of information about them, such as the website of the National Institutes of Health’s Office of Dietary Supplements, Dr. Cohen said. But patients often forget or fail to do this, which can create medical puzzles, such as the case of the woman in the Ontario case study, said Peter Lurie, MD, MPH, executive director of the nonprofit Center for Science in the Public Interest, which has pressed for increased regulation of supplements.
Clinicians need to keep in mind that patients may need prodding to reveal what supplements they are taking, he said.
“They just think of them as different, somehow not the province of the doctor,” Dr. Lurie said. “For others, they are concerned that the doctors will disapprove. So, they hide it.”
A version of this article first appeared on Medscape.com.
A woman’s quest to become pregnant resulted in lead poisoning from an Ayurvedic treatment. The case triggered the seizure of pills from an Ontario natural-products clinic and the issuance of government warnings about the risks of products from this business, according to a new report.
, including the presence of lead and other metals in Ayurvedic products, according to the report.
“When consumer products may be contaminated with lead, or when lead exposure is linked to sources in the community, involving public health can facilitate broader actions to reduce and prevent exposures to other people at risk,” wrote report author Julian Gitelman, MD, MPH, a resident physician at the University of Toronto Dalla Lana School of Public Health, and colleagues.
Their case study was published in the Canadian Medical Association Journal.
The researchers detailed what happened after a 39-year-old woman sought medical care for abdominal pain, constipation, nausea, and vomiting. The woman underwent a series of tests, including colonoscopy, laparoscopy, and biopsies of bone marrow and ovarian cysts.
Only later did clinicians home in on the cause of her ailments: the Ayurvedic medications that the patient had been taking daily for more than a year for infertility. Her daily regimen had varied, ranging from a few pills to a dozen pills.
Heavy metals are sometimes intentionally added to Ayurvedic supplements for perceived healing properties, wrote the authors. They cited a previous study of a sample of Ayurvedic pills bought on the Internet from manufacturers based in the United States and India that showed that 21% contained lead, mercury, or arsenic.
A case report published last year in German Medical Weekly raised the same issue.
Melatonin gummies
Regulators in many countries struggle to help consumers understand the risks of natural health supplements, and the challenge extends well beyond Ayurvedic products.
There has been a “huge and very troubling increase” in U.S. poison control calls associated with gummy-bear products containing melatonin, said Canadian Senator Stan Kutcher, MD, at a May 11 meeting of Canada’s Standing Senate Committee on Social Affairs, Science, and Technology.
In April, JAMA published a U.S. analysis of melatonin gummy products, Dr. Kutcher noted. In this research letter, investigators reported that one product did not contain detectable levels of melatonin but did contain 31.3 mg of cannabidiol.
In other products, the quantity of melatonin ranged from 74% to 347% of the labeled quantity. A previous Canadian study of 16 melatonin brands found that the actual dose of melatonin ranged from 17% to 478% of the declared quantity, the letter noted.
The May 11 Senate meeting provided a forum for many of the recurring debates about supplements, which also are known as natural health products.
Barry Power, PharmD, editor in chief for the Canadian Pharmacists Association, said that his group was disappointed when Canada excluded natural health products from Vanessa’s Law, which was passed in 2014. This law sought to improve the reporting of adverse reactions to drugs.
“We’re glad this is being revisited now,” Dr. Power told the Senate committee. “Although natural health products are often seen as low risk, we need to keep in mind that ‘low risk’ does not mean ‘no risk,’ and ‘natural’ does not mean ‘safe.’ ”
In contrast, Aaron Skelton, chief executive of the Canadian Health Food Association, spoke against this bid to expand the reach of Vanessa’s Law into natural health products. Canadian lawmakers attached provisions regarding increased oversight of natural health products to a budget package instead of considering them as part of a stand-alone bill.
“Our concern is that the powers that are being discussed have not been reviewed and debated,” Mr. Skelton told Dr. Kutcher. “The potential for overreach and unnecessary regulation is significant, and that deserves debate.”
“Profits should not trump Canadians’ health,” answered Dr. Kutcher, who earlier served as head of the psychiatry department at Dalhousie University in Halifax, N.S.
By June, Vanessa’s Law had been expanded with provisions that address natural health products, including the reporting of products that present a serious risk to consumers.
Educating consumers
Many consumers overestimate the level of government regulation of supplements, said Pieter A. Cohen, MD, leader of the Supplement Research Program at Cambridge Health Alliance in Massachusetts. Dr. Cohen was the lead author of the JAMA research letter about melatonin products.
Supplements often share shelves in pharmacies with medicines that are subject to more strict regulation, which causes confusion.
“It’s really hard to wrap your brain around [the fact] that a health product is being sold in pharmacies in the United States and it’s not being vetted by the FDA [U.S. Food and Drug Administration]”, Dr. Cohen said in an interview
The confusion extends across borders. Many consumers in other countries will assume that the FDA performed premarket screening of U.S.-made supplements, but that is not the case, he said.
People who want to take supplements should look for reputable sources of information about them, such as the website of the National Institutes of Health’s Office of Dietary Supplements, Dr. Cohen said. But patients often forget or fail to do this, which can create medical puzzles, such as the case of the woman in the Ontario case study, said Peter Lurie, MD, MPH, executive director of the nonprofit Center for Science in the Public Interest, which has pressed for increased regulation of supplements.
Clinicians need to keep in mind that patients may need prodding to reveal what supplements they are taking, he said.
“They just think of them as different, somehow not the province of the doctor,” Dr. Lurie said. “For others, they are concerned that the doctors will disapprove. So, they hide it.”
A version of this article first appeared on Medscape.com.
A woman’s quest to become pregnant resulted in lead poisoning from an Ayurvedic treatment. The case triggered the seizure of pills from an Ontario natural-products clinic and the issuance of government warnings about the risks of products from this business, according to a new report.
, including the presence of lead and other metals in Ayurvedic products, according to the report.
“When consumer products may be contaminated with lead, or when lead exposure is linked to sources in the community, involving public health can facilitate broader actions to reduce and prevent exposures to other people at risk,” wrote report author Julian Gitelman, MD, MPH, a resident physician at the University of Toronto Dalla Lana School of Public Health, and colleagues.
Their case study was published in the Canadian Medical Association Journal.
The researchers detailed what happened after a 39-year-old woman sought medical care for abdominal pain, constipation, nausea, and vomiting. The woman underwent a series of tests, including colonoscopy, laparoscopy, and biopsies of bone marrow and ovarian cysts.
Only later did clinicians home in on the cause of her ailments: the Ayurvedic medications that the patient had been taking daily for more than a year for infertility. Her daily regimen had varied, ranging from a few pills to a dozen pills.
Heavy metals are sometimes intentionally added to Ayurvedic supplements for perceived healing properties, wrote the authors. They cited a previous study of a sample of Ayurvedic pills bought on the Internet from manufacturers based in the United States and India that showed that 21% contained lead, mercury, or arsenic.
A case report published last year in German Medical Weekly raised the same issue.
Melatonin gummies
Regulators in many countries struggle to help consumers understand the risks of natural health supplements, and the challenge extends well beyond Ayurvedic products.
There has been a “huge and very troubling increase” in U.S. poison control calls associated with gummy-bear products containing melatonin, said Canadian Senator Stan Kutcher, MD, at a May 11 meeting of Canada’s Standing Senate Committee on Social Affairs, Science, and Technology.
In April, JAMA published a U.S. analysis of melatonin gummy products, Dr. Kutcher noted. In this research letter, investigators reported that one product did not contain detectable levels of melatonin but did contain 31.3 mg of cannabidiol.
In other products, the quantity of melatonin ranged from 74% to 347% of the labeled quantity. A previous Canadian study of 16 melatonin brands found that the actual dose of melatonin ranged from 17% to 478% of the declared quantity, the letter noted.
The May 11 Senate meeting provided a forum for many of the recurring debates about supplements, which also are known as natural health products.
Barry Power, PharmD, editor in chief for the Canadian Pharmacists Association, said that his group was disappointed when Canada excluded natural health products from Vanessa’s Law, which was passed in 2014. This law sought to improve the reporting of adverse reactions to drugs.
“We’re glad this is being revisited now,” Dr. Power told the Senate committee. “Although natural health products are often seen as low risk, we need to keep in mind that ‘low risk’ does not mean ‘no risk,’ and ‘natural’ does not mean ‘safe.’ ”
In contrast, Aaron Skelton, chief executive of the Canadian Health Food Association, spoke against this bid to expand the reach of Vanessa’s Law into natural health products. Canadian lawmakers attached provisions regarding increased oversight of natural health products to a budget package instead of considering them as part of a stand-alone bill.
“Our concern is that the powers that are being discussed have not been reviewed and debated,” Mr. Skelton told Dr. Kutcher. “The potential for overreach and unnecessary regulation is significant, and that deserves debate.”
“Profits should not trump Canadians’ health,” answered Dr. Kutcher, who earlier served as head of the psychiatry department at Dalhousie University in Halifax, N.S.
By June, Vanessa’s Law had been expanded with provisions that address natural health products, including the reporting of products that present a serious risk to consumers.
Educating consumers
Many consumers overestimate the level of government regulation of supplements, said Pieter A. Cohen, MD, leader of the Supplement Research Program at Cambridge Health Alliance in Massachusetts. Dr. Cohen was the lead author of the JAMA research letter about melatonin products.
Supplements often share shelves in pharmacies with medicines that are subject to more strict regulation, which causes confusion.
“It’s really hard to wrap your brain around [the fact] that a health product is being sold in pharmacies in the United States and it’s not being vetted by the FDA [U.S. Food and Drug Administration]”, Dr. Cohen said in an interview
The confusion extends across borders. Many consumers in other countries will assume that the FDA performed premarket screening of U.S.-made supplements, but that is not the case, he said.
People who want to take supplements should look for reputable sources of information about them, such as the website of the National Institutes of Health’s Office of Dietary Supplements, Dr. Cohen said. But patients often forget or fail to do this, which can create medical puzzles, such as the case of the woman in the Ontario case study, said Peter Lurie, MD, MPH, executive director of the nonprofit Center for Science in the Public Interest, which has pressed for increased regulation of supplements.
Clinicians need to keep in mind that patients may need prodding to reveal what supplements they are taking, he said.
“They just think of them as different, somehow not the province of the doctor,” Dr. Lurie said. “For others, they are concerned that the doctors will disapprove. So, they hide it.”
A version of this article first appeared on Medscape.com.
FROM THE CANADIAN MEDICAL ASSOCIATION JOURNAL
Atopic Dermatitis: Differential Diagnosis
Isometric exercise found optimal for lowering blood pressure?
The findings support the development of new exercise guidelines for blood pressure control, the authors said.
Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.
Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.
The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.
“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”
The study was published online in the British Journal of Sports Medicine.
All modes effective
The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.
All protocols were then stratified as AET, RT, CT, HIIT or IET.
As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.
Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.
All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.
Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).
In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).
Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.
Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.
The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.
Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
Guideline changing?
“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”
In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.
In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”
“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.
That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”
The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings support the development of new exercise guidelines for blood pressure control, the authors said.
Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.
Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.
The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.
“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”
The study was published online in the British Journal of Sports Medicine.
All modes effective
The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.
All protocols were then stratified as AET, RT, CT, HIIT or IET.
As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.
Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.
All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.
Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).
In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).
Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.
Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.
The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.
Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
Guideline changing?
“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”
In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.
In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”
“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.
That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”
The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The findings support the development of new exercise guidelines for blood pressure control, the authors said.
Previous research, based on older data that excluded high-intensity interval training (HIIT) and isometric exercise training (IET), led to aerobic exercise training (AET) being recommended for managing blood pressure, according to the authors.
Although AET, HIIT, dynamic resistance training (RT), and combined training (CT) are also effective in reducing both systolic and diastolic blood pressure, the new analysis suggests that IET does it best.
The analysis showed reductions in blood pressure of 8.24/4 mm Hg after IET, compared with 4.49/2.53 mm Hg after AET; 4.55/3.04 mm Hg after RT; 6.04/2.54 mm Hg after CT; and 4.08/2.50 mm Hg after HIIT.
“These findings mirror our smaller-scale trials, and therefore we anticipated that isometrics would be largely effective,” Jamie O’Driscoll, PhD, of Canterbury (England) Christ Church University, said in an interview. However, “the magnitude of difference between isometrics and some other modes was surprising.”
The study was published online in the British Journal of Sports Medicine.
All modes effective
The investigators analyzed data from 270 randomized controlled trials including 15,827 people published between 1990 and February 2023. For consistency, the protocol/intensity of each included paper was screened against the Exercise Prescription in Everyday Practice and Rehabilitative Training tool to be defined and categorized.
All protocols were then stratified as AET, RT, CT, HIIT or IET.
As appropriate, protocols were then further stratified into subgroups: AET included walking, running, and cycling; HIIT included sprint interval training and aerobic interval training; and IET included isometric leg extension and isometric wall squat.
Healthy resting blood pressure was defined as a reading below 130/85 mm Hg, prehypertension as 130-139/85-89 mm Hg, and hypertension as 140/90 mm Hg or higher.
All exercise modes led to statistically significant reductions in systolic BP in normal blood pressure cohorts; however, all reductions were substantially larger in individuals with hypertension.
Pairwise analyses showed significant reductions in resting systolic BP and diastolic BP following AET (−4.49/–2.53 mm Hg); RT (–4.55/–3.04 mm Hg), CT (–6.04/–2.54 mm Hg), HIT (–4.08/–2.50 mm Hg); and IET (–8.24/–4.00 mm Hg).
In the network meta-analysis, the rank order of effectiveness for systolic BP based on surface under the cumulative ranking curve values were IET (SUCRA: 98.3%), CT (75.7%), RT (46.1%), AET (40.5%), and HIIT (39.4%).
Secondary network meta-analyses showed that isometric wall squat was the most effective submode for reducing systolic BP (90.4%), followed by isometric leg extension, isometric hand grip, cycling, running, CT, sprint interval training, other aerobic, RT, aerobic interval training, and walking.
Running was the most effective submode for lowering diastolic BP (91.3%), followed by isometric wall squat, isometric handgrip, isometric leg extension, cycling, sprint interval training, RT, AIT, other aerobic, CT, and walking.
The authors acknowledged limitations, including variability in exercise interventions, missing data, variable quality of exercise monitoring and analyses, lack of blinding to group allocation, varying participant populations, and publication bias.
Nevertheless, they concluded, “the results of this analysis should inform future exercise guideline recommendations for the prevention and treatment of arterial hypertension.”
Guideline changing?
“There are numerous organizations involved in providing and communicating population exercise guidelines,” including World Health Organization, American and European exercise guidelines, and the National Institute for Health and Care Excellence, Dr. O’Driscoll said. “We are currently developing an international collaborative project with other world leaders in the area to develop this line of enquiry.”
In addition, the team is exploring the prescription of IET within England’s National Health Service and extending the study to wider clinical populations.
In a comment, John A. Osborne, MD, PhD, founder and director of State of the Heart Cardiology in Southlake, Tex., said: “This study further lends credence that other forms of exercise, beyond the usually recommended aerobic exercise promulgated in prior guidelines, have significant value for blood pressure lowering, and, potentially, may offer even greater benefits for ... controlling hypertension.”
“This study should inform contemporary nonpharmacological approaches to blood pressure management and allows providers more flexibility in different strategies of exercise to combat high blood pressure,” said Dr. Osborne, a volunteer spokesperson for the American Heart Association.
That said, “while this study by itself is extremely provocative, thoughtful, and rigorously performed, it should be used as hypothesis generating and hopefully [will be followed by] head-to-head studies of aerobic exercise versus resistance training to confirm the findings.”
The study received no funding. Dr. O’Driscoll and Dr. Osborne reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE BRITISH JOURNAL OF SPORTS MEDICINE
‘Triple G’ agonist hits new weight loss heights
A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).
This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.
The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.
The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m2 – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.
The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.
After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
Weight losses never before seen
“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.
A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.
The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.
The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.
Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
Triple agonist has added effect on liver fat clearance
The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.
A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).
That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.
“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.
The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.
The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.
Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.
The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.
The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).
This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.
The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.
The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m2 – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.
The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.
After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
Weight losses never before seen
“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.
A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.
The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.
The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.
Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
Triple agonist has added effect on liver fat clearance
The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.
A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).
That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.
“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.
The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.
The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.
Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.
The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.
The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
A novel triple agonist to receptors for three nutrient-stimulated hormones led to weight loss as high as 24% among people with overweight or obesity but who did not have type 2 diabetes when used at the highest tested dose for 48 weeks. The results are from a phase 2 study of retatrutide that was published in The New England Journal of Medicine (2023 Aug 10. doi: 10.1056/NEJMoa2301972).
This level of weight loss is “unprecedented” for a medication administered for 48 weeks, Mary-Elizabeth Patti, MD, said in an editorial that accompanied the report.
The findings “offer further optimism ... that effective pharmacologic management of obesity and related disorders is possible,” wrote Dr. Patti, a principal investigator at the Joslin Diabetes Center in Boston.
The study randomly assigned 338 adults with obesity or overweight – a body mass index (BMI) of ≥ 27 kg/m2 – and at least one weight-related complication to receive either weekly subcutaneous injections of retatrutide in any of six dose regimens or placebo over 48 weeks. The primary outcome was weight change from baseline after 24 weeks.
The highest dose of retatrutide safely produced an average 17.5% drop from baseline weight, compared with an average 1.6% reduction in the placebo group, after 24 weeks, a significant difference.
After 48 weeks, the highest retatrutide dose safely cut baseline weight by an average of 24.2%, compared with an average 2.1% drop among placebo control patients, Ania M. Jastreboff, MD, PhD, and her coauthors wrote in their report. Weight loss levels after 24 and 48 weeks of retatrutide treatment followed a clear dose-response pattern.
Weight losses never before seen
“I have never seen weight loss at this level” after nearly 1 year of treatment, Dr. Jastreboff said when she discussed these findings in a press conference at the annual scientific sessions of the American Diabetes Association in San Diego in late June.
A separate presentation at the ADA meeting documented unprecedented weight loss levels in a study of 281 people with obesity or overweight and type 2 diabetes.
“No other medication has shown an average 17% reduction from baseline bodyweight after 36 weeks in people with type 2 diabetes,” said Julio Rosenstock, MD, director of the Dallas Diabetes Research Center at Medical City, Texas, who formally presented the results from the study of retatrutide in people with type 2 diabetes at the ADA meeting.
The mechanism behind retatrutide’s potent weight-loss effect seems likely tied to its action on three human receptors that naturally respond to three nutrient-stimulated hormones that control appetite, metabolism, fat mobilization, and related functions.
The three hormones that the retatrutide molecule simultaneously mimics are glucagon-like peptide-1 (GLP-1), such as agents in the class of GLP-1 agonists that includes liraglutide (Victoza/Saxenda) and semaglutide (Ozempic/Wegovy); the glucose-dependent insulinotropic polypeptide (GIP), the receptor that is also activated by tirzepatide (Mounjaro), a dual-incretin receptor agonist that mimics both GLP-1 and GIP; and glucagon. Survodutide is a dual GLP-1 and glucagon receptor agonist in phase 2 development.
Retatrutide is currently unique among agents with reported clinical results by having agonist effects on the receptors for all three of these hormones, a property that led Dr. Patti to call retatrutide a “triple G” hormone-receptor agonist in her editorial.
Triple agonist has added effect on liver fat clearance
The glucagon-receptor agonism appears to give retatrutide added effects beyond those of the GLP-1 agonists or GLP-1/GIP dual agonists that are increasingly used in U.S. practice.
A prespecified subgroup analysis of the no diabetes/Jastreboff study (but that was not included in the NEJM report) showed that at both 8-mg and 12-mg weekly doses, 24 weeks of retatrutide produced complete resolution of excess liver fat (hepatic steatosis) in about 80% of the people eligible for the analysis (those whose liver volume was at least 10% fat at study entry).
That percentage increased to about 90% of people receiving these doses after 48 weeks, Lee M. Kaplan, MD, reported during a separate presentation at the ADA meeting.
“When you add glucagon activity, liver-fat clearance goes up tremendously,” observed Dr. Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital in Boston.
The average age of the participants in the new study of the use of retatrutide for those with obesity/overweight but not diabetes was 48 years. By design, 52% were men. (The study sought to enroll roughly equal numbers of men and women.) Average BMI at study entry was 37 kg/m2.
Treatment with retatrutide was also significantly associated with improvements in several cardiometabolic measures in exploratory analyses, including systolic and diastolic blood pressure, A1c, fasting glucose, insulin, and some (but not all) lipids, Dr. Jastreboff, director of the Yale Obesity Research Center of Yale University in New Haven, Conn., and her coauthors reported in the NEJM article.
The safety profile of retatrutide was consistent with reported phase 1 findings for the agent among people with type 2 diabetes and resembled the safety profiles of other agents based on GLP-1 or GIP–GLP-1 mimicry for the treatment of type 2 diabetes or obesity.
The most frequently reported adverse events from retatrutide were transient, mostly mild to moderate gastrointestinal events. They occurred primarily during dose escalation. Discontinuation of retatrutide or placebo because of adverse events occurred in 6% to 16% of the participants who received retatrutide and in none of the participants who received placebo.
Lilly, the company developing retatrutide, previously announced the launch of four phase 3 trials to gather further data on retatrutide for use in a marketing-approval application to the Food and Drug Administration.
The four trials – TRIUMPH-1, TRIUMPH-2, TRIUMPH-3, and TRIUMPH-4 – are evaluating the safety and efficacy of retatrutide for chronic weight management for those with obesity or overweight, including those who also have obstructive sleep apnea, knee osteoarthritis, type 2 diabetes, or cardiovascular disease.
The study was sponsored by Lilly, the company developing retatrutide. Dr. Patti has been a consultant to AstraZeneca, Dexcom, Hanmi, and MBX. She has received funding from Dexcom and has been a monitor for a trial funded by Fractyl. Dr. Jastreboff, Dr. Kaplan, and Dr. Rosenstock have reported financial relationships with Lilly as well as other companies.
A version of this article first appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Upper airway ultrasound: Easy to learn, facile to use!
Thoracic Oncology & Chest Procedures Network
Ultrasound & Chest Imaging Section
Point-of-care ultrasound (POCUS) is integral to the delivery of high-quality patient care. The benefits of POCUS for timely diagnosis and procedural assistance are well documented. With continued innovation, its novel benefits can extend to the upper airway evaluation in both inpatient and outpatient settings.
Adi et al notes that POCUS can serve as an adjunct to traditional airway checklists and help intensivists/anesthesiologists identify potentially difficult laryngoscopies, choose the correct endotracheal tube size to reduce the risk of subglottic stenosis, and help confirm appropriate endotracheal tube placement (Adi, et al. J Emerg Crit Care Med. 2019;3:31).
The prediction of a difficult airway is a potentially lifesaving use for this technology. The authors note that smaller studies demonstrate promising results in four techniques: the inability to visualize the hyoid bone using the sublingual approach, a shorter hyomental distance in morbidly obese patients, anterior neck thickness at different anatomical levels (vocal cords, hyoid bone, and thyroid membrane), and a tongue thickness of more than 6.1 cm from the submental approach were all capable of predicting difficult tracheal intubation with varying degrees of sensitivity and specificity.
In the outpatient setting, an understanding of the upper airway anatomy can help with sleep apnea screenings. Korotun, et al. demonstrated in a small sample that ultrasound evaluation of hyoid bone excursion during hypoglossal nerve stimulation may be a useful tool to predict response to therapy and guide hypoglossal nerve stimulator settings (Korotun, et al. Sleep. 2020;43[Suppl_1]:A247-A248).Upper airway ultrasound is easy to learn. The anatomical landmarks are similar in most patients. This convenient tool can be added to your patient care repertoire in a variety of clinical settings.
Sameer Khanijo, MD, FCCP
Section Member-at-Large
Navitha Ramesh, MD, FCCP
Section Vice-Chair
Thoracic Oncology & Chest Procedures Network
Ultrasound & Chest Imaging Section
Point-of-care ultrasound (POCUS) is integral to the delivery of high-quality patient care. The benefits of POCUS for timely diagnosis and procedural assistance are well documented. With continued innovation, its novel benefits can extend to the upper airway evaluation in both inpatient and outpatient settings.
Adi et al notes that POCUS can serve as an adjunct to traditional airway checklists and help intensivists/anesthesiologists identify potentially difficult laryngoscopies, choose the correct endotracheal tube size to reduce the risk of subglottic stenosis, and help confirm appropriate endotracheal tube placement (Adi, et al. J Emerg Crit Care Med. 2019;3:31).
The prediction of a difficult airway is a potentially lifesaving use for this technology. The authors note that smaller studies demonstrate promising results in four techniques: the inability to visualize the hyoid bone using the sublingual approach, a shorter hyomental distance in morbidly obese patients, anterior neck thickness at different anatomical levels (vocal cords, hyoid bone, and thyroid membrane), and a tongue thickness of more than 6.1 cm from the submental approach were all capable of predicting difficult tracheal intubation with varying degrees of sensitivity and specificity.
In the outpatient setting, an understanding of the upper airway anatomy can help with sleep apnea screenings. Korotun, et al. demonstrated in a small sample that ultrasound evaluation of hyoid bone excursion during hypoglossal nerve stimulation may be a useful tool to predict response to therapy and guide hypoglossal nerve stimulator settings (Korotun, et al. Sleep. 2020;43[Suppl_1]:A247-A248).Upper airway ultrasound is easy to learn. The anatomical landmarks are similar in most patients. This convenient tool can be added to your patient care repertoire in a variety of clinical settings.
Sameer Khanijo, MD, FCCP
Section Member-at-Large
Navitha Ramesh, MD, FCCP
Section Vice-Chair
Thoracic Oncology & Chest Procedures Network
Ultrasound & Chest Imaging Section
Point-of-care ultrasound (POCUS) is integral to the delivery of high-quality patient care. The benefits of POCUS for timely diagnosis and procedural assistance are well documented. With continued innovation, its novel benefits can extend to the upper airway evaluation in both inpatient and outpatient settings.
Adi et al notes that POCUS can serve as an adjunct to traditional airway checklists and help intensivists/anesthesiologists identify potentially difficult laryngoscopies, choose the correct endotracheal tube size to reduce the risk of subglottic stenosis, and help confirm appropriate endotracheal tube placement (Adi, et al. J Emerg Crit Care Med. 2019;3:31).
The prediction of a difficult airway is a potentially lifesaving use for this technology. The authors note that smaller studies demonstrate promising results in four techniques: the inability to visualize the hyoid bone using the sublingual approach, a shorter hyomental distance in morbidly obese patients, anterior neck thickness at different anatomical levels (vocal cords, hyoid bone, and thyroid membrane), and a tongue thickness of more than 6.1 cm from the submental approach were all capable of predicting difficult tracheal intubation with varying degrees of sensitivity and specificity.
In the outpatient setting, an understanding of the upper airway anatomy can help with sleep apnea screenings. Korotun, et al. demonstrated in a small sample that ultrasound evaluation of hyoid bone excursion during hypoglossal nerve stimulation may be a useful tool to predict response to therapy and guide hypoglossal nerve stimulator settings (Korotun, et al. Sleep. 2020;43[Suppl_1]:A247-A248).Upper airway ultrasound is easy to learn. The anatomical landmarks are similar in most patients. This convenient tool can be added to your patient care repertoire in a variety of clinical settings.
Sameer Khanijo, MD, FCCP
Section Member-at-Large
Navitha Ramesh, MD, FCCP
Section Vice-Chair
Addressing disparities in goals-of-care conversations
Critical Care Network
Nonrespiratory Critical Care Section
Goals-of-care discussions are essential to management of the intensive care unit (ICU) patient. Racial inequities in end-of-life decision making have been documented for many years, with literature demonstrating that marginalized populations are less likely to have EHR-documented goals-of-care discussions and more likely to have concerns regarding clinician communication.
A recently published randomized control trial in JAMA highlights an intervention that offers promise in addressing disparities in goals-of-care conversations. Curtis, et al. studied whether priming physicians with a communication guide advising on discussion prompts and language for goals-of-care could improve the rate of documented goals-of-care discussions among hospitalized older adults with serious illness. The study found that for patients in the intervention arm, there was a significant increase in proportion of goals-of-care discussions within 30 days. Notably, the difference in documented goals-of-care discussions between arms was greater in the subgroup of patients from underserved groups (Curtis JR, et al. JAMA. 2023;329[23]:2028-37).
Nevertheless, while interventions may help increase the rate of goals-of-care discussions, it is also important to address the content of discussions themselves. You and colleagues recently published a mixed-methods study assessing the impact of race on shared decision-making behaviors during family/caregiver meetings. The authors found that while ICU physicians approached shared decision making with White and Black families similarly, Black families felt their physicians provided less validation of the family role in decision making than White families did (You H, et al. Ann Am Thorac Soc. 2023 May;20[5]:759-62). These findings highlight the importance of ongoing work that focuses not only on quantity but also on quality of communication regarding goals-of-care for patients from diverse backgrounds.
Divya Shankar MD
Section Fellow-in-Training
Muhammad Hayat-Syed MD
Section Vice Chair
Critical Care Network
Nonrespiratory Critical Care Section
Goals-of-care discussions are essential to management of the intensive care unit (ICU) patient. Racial inequities in end-of-life decision making have been documented for many years, with literature demonstrating that marginalized populations are less likely to have EHR-documented goals-of-care discussions and more likely to have concerns regarding clinician communication.
A recently published randomized control trial in JAMA highlights an intervention that offers promise in addressing disparities in goals-of-care conversations. Curtis, et al. studied whether priming physicians with a communication guide advising on discussion prompts and language for goals-of-care could improve the rate of documented goals-of-care discussions among hospitalized older adults with serious illness. The study found that for patients in the intervention arm, there was a significant increase in proportion of goals-of-care discussions within 30 days. Notably, the difference in documented goals-of-care discussions between arms was greater in the subgroup of patients from underserved groups (Curtis JR, et al. JAMA. 2023;329[23]:2028-37).
Nevertheless, while interventions may help increase the rate of goals-of-care discussions, it is also important to address the content of discussions themselves. You and colleagues recently published a mixed-methods study assessing the impact of race on shared decision-making behaviors during family/caregiver meetings. The authors found that while ICU physicians approached shared decision making with White and Black families similarly, Black families felt their physicians provided less validation of the family role in decision making than White families did (You H, et al. Ann Am Thorac Soc. 2023 May;20[5]:759-62). These findings highlight the importance of ongoing work that focuses not only on quantity but also on quality of communication regarding goals-of-care for patients from diverse backgrounds.
Divya Shankar MD
Section Fellow-in-Training
Muhammad Hayat-Syed MD
Section Vice Chair
Critical Care Network
Nonrespiratory Critical Care Section
Goals-of-care discussions are essential to management of the intensive care unit (ICU) patient. Racial inequities in end-of-life decision making have been documented for many years, with literature demonstrating that marginalized populations are less likely to have EHR-documented goals-of-care discussions and more likely to have concerns regarding clinician communication.
A recently published randomized control trial in JAMA highlights an intervention that offers promise in addressing disparities in goals-of-care conversations. Curtis, et al. studied whether priming physicians with a communication guide advising on discussion prompts and language for goals-of-care could improve the rate of documented goals-of-care discussions among hospitalized older adults with serious illness. The study found that for patients in the intervention arm, there was a significant increase in proportion of goals-of-care discussions within 30 days. Notably, the difference in documented goals-of-care discussions between arms was greater in the subgroup of patients from underserved groups (Curtis JR, et al. JAMA. 2023;329[23]:2028-37).
Nevertheless, while interventions may help increase the rate of goals-of-care discussions, it is also important to address the content of discussions themselves. You and colleagues recently published a mixed-methods study assessing the impact of race on shared decision-making behaviors during family/caregiver meetings. The authors found that while ICU physicians approached shared decision making with White and Black families similarly, Black families felt their physicians provided less validation of the family role in decision making than White families did (You H, et al. Ann Am Thorac Soc. 2023 May;20[5]:759-62). These findings highlight the importance of ongoing work that focuses not only on quantity but also on quality of communication regarding goals-of-care for patients from diverse backgrounds.
Divya Shankar MD
Section Fellow-in-Training
Muhammad Hayat-Syed MD
Section Vice Chair
Use of frailty assessment in lung transplant evaluation
Diffuse Lung Disease & Transplant Network
Lung Transplant Section
Frailty, a concept that originated in the geriatric population, is a state of vulnerability resulting from a decline in reserve and function across physiological systems. While it is more commonly observed in older adults, some aging-associated syndromes, such as sarcopenia, impaired cognition, inflammation, and malnutrition, may be present in younger patients with end-stage organ disease. These syndromes can be associated with biological age, as opposed to chronological age, which explains why younger patients with end-stage organ disease can develop frailty (Schaenman JM, et al. Am J Transplant. 2021 Jun;21[6]:2018-24). Frailty in the lung transplant population is associated with increased morbidity and mortality while on the waitlist and post-transplant (Montgomery E, et al. J Transplant. 2020 Aug 7:3239495). In 2021, the International Society of Heart and Lung Transplantation recommended including a frailty assessment to complete a patient’s transplant evaluation. The committee cautioned using current assessment tools, as they are not yet accepted as the standard of care (Leard, et al. J Heart Lung Transplant. 2021 Nov;40[11]:1349-79). Existing tools being used evolved from studies of community-dwelling older adults with no predilection for distinct organ disease, which include the Fried Physical Frailty Phenotype (FPFP) and the Short Physical Performance Battery (SPPB). Along with physical limitations, frail patients tend to have abnormal biomarkers including higher inflammatory cytokines, such as plasma IL-6 and tumor necrosis factor receptor 1, and lower insulin-like growth factor I and leptin (Singer JP, et al. Am J Respir Crit Care Med. 2015;192[11]1325-34). The concept of a lung-focused approach to frailty, which considers biomarkers and body composition, is currently being researched (Singer JP, et al. J Heart Lung Transplant. 2023;S1053-S2498[23]00049-9). This disease-specific frailty scale would identify lung transplant candidates who may benefit from targeted interventions, and such frailty would also be expected to improve after transplant.
Erin Meier, MD
Section Fellow-in-Training
Anupam Kumar, MD, FCCP
Section Member-at-Large
Diffuse Lung Disease & Transplant Network
Lung Transplant Section
Frailty, a concept that originated in the geriatric population, is a state of vulnerability resulting from a decline in reserve and function across physiological systems. While it is more commonly observed in older adults, some aging-associated syndromes, such as sarcopenia, impaired cognition, inflammation, and malnutrition, may be present in younger patients with end-stage organ disease. These syndromes can be associated with biological age, as opposed to chronological age, which explains why younger patients with end-stage organ disease can develop frailty (Schaenman JM, et al. Am J Transplant. 2021 Jun;21[6]:2018-24). Frailty in the lung transplant population is associated with increased morbidity and mortality while on the waitlist and post-transplant (Montgomery E, et al. J Transplant. 2020 Aug 7:3239495). In 2021, the International Society of Heart and Lung Transplantation recommended including a frailty assessment to complete a patient’s transplant evaluation. The committee cautioned using current assessment tools, as they are not yet accepted as the standard of care (Leard, et al. J Heart Lung Transplant. 2021 Nov;40[11]:1349-79). Existing tools being used evolved from studies of community-dwelling older adults with no predilection for distinct organ disease, which include the Fried Physical Frailty Phenotype (FPFP) and the Short Physical Performance Battery (SPPB). Along with physical limitations, frail patients tend to have abnormal biomarkers including higher inflammatory cytokines, such as plasma IL-6 and tumor necrosis factor receptor 1, and lower insulin-like growth factor I and leptin (Singer JP, et al. Am J Respir Crit Care Med. 2015;192[11]1325-34). The concept of a lung-focused approach to frailty, which considers biomarkers and body composition, is currently being researched (Singer JP, et al. J Heart Lung Transplant. 2023;S1053-S2498[23]00049-9). This disease-specific frailty scale would identify lung transplant candidates who may benefit from targeted interventions, and such frailty would also be expected to improve after transplant.
Erin Meier, MD
Section Fellow-in-Training
Anupam Kumar, MD, FCCP
Section Member-at-Large
Diffuse Lung Disease & Transplant Network
Lung Transplant Section
Frailty, a concept that originated in the geriatric population, is a state of vulnerability resulting from a decline in reserve and function across physiological systems. While it is more commonly observed in older adults, some aging-associated syndromes, such as sarcopenia, impaired cognition, inflammation, and malnutrition, may be present in younger patients with end-stage organ disease. These syndromes can be associated with biological age, as opposed to chronological age, which explains why younger patients with end-stage organ disease can develop frailty (Schaenman JM, et al. Am J Transplant. 2021 Jun;21[6]:2018-24). Frailty in the lung transplant population is associated with increased morbidity and mortality while on the waitlist and post-transplant (Montgomery E, et al. J Transplant. 2020 Aug 7:3239495). In 2021, the International Society of Heart and Lung Transplantation recommended including a frailty assessment to complete a patient’s transplant evaluation. The committee cautioned using current assessment tools, as they are not yet accepted as the standard of care (Leard, et al. J Heart Lung Transplant. 2021 Nov;40[11]:1349-79). Existing tools being used evolved from studies of community-dwelling older adults with no predilection for distinct organ disease, which include the Fried Physical Frailty Phenotype (FPFP) and the Short Physical Performance Battery (SPPB). Along with physical limitations, frail patients tend to have abnormal biomarkers including higher inflammatory cytokines, such as plasma IL-6 and tumor necrosis factor receptor 1, and lower insulin-like growth factor I and leptin (Singer JP, et al. Am J Respir Crit Care Med. 2015;192[11]1325-34). The concept of a lung-focused approach to frailty, which considers biomarkers and body composition, is currently being researched (Singer JP, et al. J Heart Lung Transplant. 2023;S1053-S2498[23]00049-9). This disease-specific frailty scale would identify lung transplant candidates who may benefit from targeted interventions, and such frailty would also be expected to improve after transplant.
Erin Meier, MD
Section Fellow-in-Training
Anupam Kumar, MD, FCCP
Section Member-at-Large
DPP1 a promising target for bronchiectasis
Airway Disorders Network
Bronchiectasis Section
and persistent inflammation. In bronchiectasis, excessive neutrophil accumulation in the airways leads to release of neutrophil serine proteases (NSPs), which contributes to tissue damage and perpetuates the inflammatory process in the lungs. The three main NSPs include neutrophil elastase (NE), proteinase3, and cathepsin G. Elevations in NE activity in sputum in NCFBE are associated with increased exacerbations and declines in lung function. Dipeptidyl peptidase 1 (DPP1), an enzyme primarily found in neutrophils, is responsible for activating NSPs during neutrophil maturation. In bronchiectasis, increased DPP1 activity results in an augmented production of active NSPs, exacerbating lung damage and inflammation.
Brensocatib, an oral, reversible inhibitor of DPP1 is currently being developed as a novel approach to managing bronchiectasis. Brensocatib was evaluated in a phase 2 clinical trial (WILLOW), a randomized, double-blind, placebo-controlled trial involving adults with non–cystic fibrosis bronchiectasis (NCFBE). Treatment with brensocatib for 24 weeks significantly prolonged the time to the first exacerbation at both the 10 mg and 25 mg doses and lowered the risk of exacerbation by 40% relative to placebo. The treatment was well tolerated, with no significant safety concerns. Results of a recent post hoc analysis from the WILLOW study show that brensocatib effectively reduces exacerbations and slows lung function decline across different severities of bronchiectasis. These findings suggest that brensocatib holds potential as the 1st new therapeutic option for patients with NCFBE, with currently no FDA-approved drugs. Results of a larger-scale phase 3 trial are awaited later this year, which will hopefully confirm these results and ascertain the long-term safety.
Shyamsunder Subramanian, MD, MBBS, FCCP
Section Chair
Airway Disorders Network
Bronchiectasis Section
and persistent inflammation. In bronchiectasis, excessive neutrophil accumulation in the airways leads to release of neutrophil serine proteases (NSPs), which contributes to tissue damage and perpetuates the inflammatory process in the lungs. The three main NSPs include neutrophil elastase (NE), proteinase3, and cathepsin G. Elevations in NE activity in sputum in NCFBE are associated with increased exacerbations and declines in lung function. Dipeptidyl peptidase 1 (DPP1), an enzyme primarily found in neutrophils, is responsible for activating NSPs during neutrophil maturation. In bronchiectasis, increased DPP1 activity results in an augmented production of active NSPs, exacerbating lung damage and inflammation.
Brensocatib, an oral, reversible inhibitor of DPP1 is currently being developed as a novel approach to managing bronchiectasis. Brensocatib was evaluated in a phase 2 clinical trial (WILLOW), a randomized, double-blind, placebo-controlled trial involving adults with non–cystic fibrosis bronchiectasis (NCFBE). Treatment with brensocatib for 24 weeks significantly prolonged the time to the first exacerbation at both the 10 mg and 25 mg doses and lowered the risk of exacerbation by 40% relative to placebo. The treatment was well tolerated, with no significant safety concerns. Results of a recent post hoc analysis from the WILLOW study show that brensocatib effectively reduces exacerbations and slows lung function decline across different severities of bronchiectasis. These findings suggest that brensocatib holds potential as the 1st new therapeutic option for patients with NCFBE, with currently no FDA-approved drugs. Results of a larger-scale phase 3 trial are awaited later this year, which will hopefully confirm these results and ascertain the long-term safety.
Shyamsunder Subramanian, MD, MBBS, FCCP
Section Chair
Airway Disorders Network
Bronchiectasis Section
and persistent inflammation. In bronchiectasis, excessive neutrophil accumulation in the airways leads to release of neutrophil serine proteases (NSPs), which contributes to tissue damage and perpetuates the inflammatory process in the lungs. The three main NSPs include neutrophil elastase (NE), proteinase3, and cathepsin G. Elevations in NE activity in sputum in NCFBE are associated with increased exacerbations and declines in lung function. Dipeptidyl peptidase 1 (DPP1), an enzyme primarily found in neutrophils, is responsible for activating NSPs during neutrophil maturation. In bronchiectasis, increased DPP1 activity results in an augmented production of active NSPs, exacerbating lung damage and inflammation.
Brensocatib, an oral, reversible inhibitor of DPP1 is currently being developed as a novel approach to managing bronchiectasis. Brensocatib was evaluated in a phase 2 clinical trial (WILLOW), a randomized, double-blind, placebo-controlled trial involving adults with non–cystic fibrosis bronchiectasis (NCFBE). Treatment with brensocatib for 24 weeks significantly prolonged the time to the first exacerbation at both the 10 mg and 25 mg doses and lowered the risk of exacerbation by 40% relative to placebo. The treatment was well tolerated, with no significant safety concerns. Results of a recent post hoc analysis from the WILLOW study show that brensocatib effectively reduces exacerbations and slows lung function decline across different severities of bronchiectasis. These findings suggest that brensocatib holds potential as the 1st new therapeutic option for patients with NCFBE, with currently no FDA-approved drugs. Results of a larger-scale phase 3 trial are awaited later this year, which will hopefully confirm these results and ascertain the long-term safety.
Shyamsunder Subramanian, MD, MBBS, FCCP
Section Chair
Celebrating the inaugural issues of CHEST’s new open access journals
After much anticipation, the inaugural issues of both CHEST® Critical Care and CHEST® Pulmonary officially launched in late June. – promoting transparency, inclusiveness, and collaboration in research – and offer authors more avenues to share their practice-changing research.
The first issue of CHEST Critical Care featured research into ICU mortality across prepandemic and pandemic cohorts in resource-limited settings in South Africa, an exploration into symptom trajectory in recipients of hematopoietic stem-cell transplantation, a narrative review of post-intensive care syndrome, and an investigation into early echocardiographic and ultrasonographic findings in critically ill patients with COVID-19.
In addition, an editorial from Hayley Gershengorn, MD, Editor in Chief of CHEST Critical Care, offers readers more insights into the need for a publication focused on the breadth of clinical topics in critical care and her goals for the new publication.
“I’m ecstatic for this launch. We are grateful to our authors for the trust they put in us and are excited to share their work with our critical care colleagues around the world,” Dr. Gershengorn said. “The editorial team and the American College of Chest Physicians staff have worked tirelessly on this journal, and it’s incredibly gratifying to see the first issue publish.”
Read the full issue and new research from the journal at www.chestcc.org.
In his own editorial featured in the inaugural issue of CHEST Pulmonary, Editor in Chief Matthew Miles, MD, MEd, FCCP, shares how the flagship journal’s proud heritage of sharing impactful clinical research – and the need to target areas of pulmonary and sleep medicine research not covered by other journals – inspired the creation of this new publication.
The issue also includes research into mobile health opportunities for asthma management, an exploration into telemedicine for patients with interstitial lung diseases, an in-depth review into the rare and often underdiagnosed disorder primary ciliary dyskinesia, research on the impact of the social vulnerability index on pulmonary embolism mortality, and an investigation into pneumothorax complications after percutaneous lung biopsy.
“I am deeply grateful to our authors, reviewers, editorial board, and staff who have contributed to the launch of our first issue,” Dr. Miles said. “The journal CHEST is known for excellence in clinically relevant research and patient management guidance. CHEST Pulmonary expands the CHEST portfolio with additional opportunity for researchers to share their work in an exclusively open access format to reach the broadest possible audience. I know our readers will enjoy learning from the research and reviews in issue one.”
Review the full issue and new articles from CHEST Pulmonary at www.chestpulmonary.org.
After much anticipation, the inaugural issues of both CHEST® Critical Care and CHEST® Pulmonary officially launched in late June. – promoting transparency, inclusiveness, and collaboration in research – and offer authors more avenues to share their practice-changing research.
The first issue of CHEST Critical Care featured research into ICU mortality across prepandemic and pandemic cohorts in resource-limited settings in South Africa, an exploration into symptom trajectory in recipients of hematopoietic stem-cell transplantation, a narrative review of post-intensive care syndrome, and an investigation into early echocardiographic and ultrasonographic findings in critically ill patients with COVID-19.
In addition, an editorial from Hayley Gershengorn, MD, Editor in Chief of CHEST Critical Care, offers readers more insights into the need for a publication focused on the breadth of clinical topics in critical care and her goals for the new publication.
“I’m ecstatic for this launch. We are grateful to our authors for the trust they put in us and are excited to share their work with our critical care colleagues around the world,” Dr. Gershengorn said. “The editorial team and the American College of Chest Physicians staff have worked tirelessly on this journal, and it’s incredibly gratifying to see the first issue publish.”
Read the full issue and new research from the journal at www.chestcc.org.
In his own editorial featured in the inaugural issue of CHEST Pulmonary, Editor in Chief Matthew Miles, MD, MEd, FCCP, shares how the flagship journal’s proud heritage of sharing impactful clinical research – and the need to target areas of pulmonary and sleep medicine research not covered by other journals – inspired the creation of this new publication.
The issue also includes research into mobile health opportunities for asthma management, an exploration into telemedicine for patients with interstitial lung diseases, an in-depth review into the rare and often underdiagnosed disorder primary ciliary dyskinesia, research on the impact of the social vulnerability index on pulmonary embolism mortality, and an investigation into pneumothorax complications after percutaneous lung biopsy.
“I am deeply grateful to our authors, reviewers, editorial board, and staff who have contributed to the launch of our first issue,” Dr. Miles said. “The journal CHEST is known for excellence in clinically relevant research and patient management guidance. CHEST Pulmonary expands the CHEST portfolio with additional opportunity for researchers to share their work in an exclusively open access format to reach the broadest possible audience. I know our readers will enjoy learning from the research and reviews in issue one.”
Review the full issue and new articles from CHEST Pulmonary at www.chestpulmonary.org.
After much anticipation, the inaugural issues of both CHEST® Critical Care and CHEST® Pulmonary officially launched in late June. – promoting transparency, inclusiveness, and collaboration in research – and offer authors more avenues to share their practice-changing research.
The first issue of CHEST Critical Care featured research into ICU mortality across prepandemic and pandemic cohorts in resource-limited settings in South Africa, an exploration into symptom trajectory in recipients of hematopoietic stem-cell transplantation, a narrative review of post-intensive care syndrome, and an investigation into early echocardiographic and ultrasonographic findings in critically ill patients with COVID-19.
In addition, an editorial from Hayley Gershengorn, MD, Editor in Chief of CHEST Critical Care, offers readers more insights into the need for a publication focused on the breadth of clinical topics in critical care and her goals for the new publication.
“I’m ecstatic for this launch. We are grateful to our authors for the trust they put in us and are excited to share their work with our critical care colleagues around the world,” Dr. Gershengorn said. “The editorial team and the American College of Chest Physicians staff have worked tirelessly on this journal, and it’s incredibly gratifying to see the first issue publish.”
Read the full issue and new research from the journal at www.chestcc.org.
In his own editorial featured in the inaugural issue of CHEST Pulmonary, Editor in Chief Matthew Miles, MD, MEd, FCCP, shares how the flagship journal’s proud heritage of sharing impactful clinical research – and the need to target areas of pulmonary and sleep medicine research not covered by other journals – inspired the creation of this new publication.
The issue also includes research into mobile health opportunities for asthma management, an exploration into telemedicine for patients with interstitial lung diseases, an in-depth review into the rare and often underdiagnosed disorder primary ciliary dyskinesia, research on the impact of the social vulnerability index on pulmonary embolism mortality, and an investigation into pneumothorax complications after percutaneous lung biopsy.
“I am deeply grateful to our authors, reviewers, editorial board, and staff who have contributed to the launch of our first issue,” Dr. Miles said. “The journal CHEST is known for excellence in clinically relevant research and patient management guidance. CHEST Pulmonary expands the CHEST portfolio with additional opportunity for researchers to share their work in an exclusively open access format to reach the broadest possible audience. I know our readers will enjoy learning from the research and reviews in issue one.”
Review the full issue and new articles from CHEST Pulmonary at www.chestpulmonary.org.