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A Single Meatless Meal Can Benefit Patients With Cirrhosis
Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.
, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.
However, changing from meat-based to non–meat-based meals is difficult to do over a long period.
“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”
“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”
The study was published online on May 2 in Clinical and Translational Gastroenterology.
Meal Type Affects Ammonia Levels Differently
The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.
The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.
Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.
In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.
Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.
The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.
Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.
In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.
The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.
“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.
The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.
Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”
Positive Results From a Simple Change
Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.
“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”
Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”
Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.
The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.
, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.
However, changing from meat-based to non–meat-based meals is difficult to do over a long period.
“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”
“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”
The study was published online on May 2 in Clinical and Translational Gastroenterology.
Meal Type Affects Ammonia Levels Differently
The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.
The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.
Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.
In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.
Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.
The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.
Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.
In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.
The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.
“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.
The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.
Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”
Positive Results From a Simple Change
Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.
“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”
Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”
Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.
The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Replacing meat with plant-based proteins for just one meal reduced ammonia levels in patients with cirrhosis, a proof-of-concept study showed.
, according to Jasmohan Bajaj, MD, a gastroenterologist at Virginia Commonwealth University School of Medicine and the Richmond VA Medical Center, Richmond, Virginia, and colleagues.
However, changing from meat-based to non–meat-based meals is difficult to do over a long period.
“Previous studies have changed people’s diets completely, expecting them to be on a meatless or vegetarian diet with a similar amount of protein when they’ve been eating meat their entire life,” Dr. Bajaj told this news organization. “That’s not really sustainable in the long run.”
“Our hope is that occasional meal substitutions would be beneficial,” he said. “This study is a first step toward seeing if that works.”
The study was published online on May 2 in Clinical and Translational Gastroenterology.
Meal Type Affects Ammonia Levels Differently
The researchers randomized 30 men with cirrhosis and on a traditional Western meat-based diet into three groups, where they received a pork/beef burger, a vegetarian bean burger, or a burger made of vegan meat substitute. The burgers provided 20 g of protein each, and all meals contained low-fat potato chips, a whole-grain bun, water, and no condiments.
The participants’ median age was 66 years in the meat and vegetarian arms and 71 years in the vegan arm. About half had diabetes, and half had prior HE and were evenly distributed across the treatment arms. Cirrhosis etiologies included hepatitis C virus infection, alcohol, and metabolic-associated steatohepatitis.
Stool microbiome characteristics, changes in ammonia, and metabolomics were compared between and within groups.
In the 3 days prior to the intervention, participants had similar intakes of red meat, poultry, fish, eggs, bread, cheese, rice, fruits, vegetables, yogurt, coffee, tea, and carbonated caffeinated and decaffeinated beverages.
Blood for metabolomics and ammonia was drawn at baseline and hourly for 3 hours post-meal while patients were under observation. All participants completed the entire meal, as shown subsequently by markers of food consumption, and none developed HE symptoms during the observation period.
The composition of the stool microbiome was similar at baseline across groups and remained unchanged. However, serum ammonia increased from baseline in the meat group but not in the vegetarian or vegan groups. The serum microbiome was not analyzed because of the low yield.
Serum metabolomics showed beneficial changes over time associated with branched-chain amino acid metabolism and urea cycle, phospholipid, and acylcarnitine levels in the vegetarian and vegan meal groups compared with the meat-based group.
In contrast, alterations in lipid profiles (higher sphingomyelins and lower lysophospholipids) were seen in the meat group.
The study was limited by its relatively small sample size, focus on the impact of only one meal, and lack of clinical outcomes, sarcopenia assessment, cognitive testing, or urine collection.
“Intermittent meat substitution with vegan or vegetarian alternatives could be helpful in reducing ammonia generation in cirrhosis,” the authors concluded.
The next step “is to substitute one meal two or three times a week, so we can move forward with this analysis and eventually be able to show that the liver is in better shape,” Dr. Bajaj said.
Meanwhile, clinicians should encourage patients with liver disease who eat meat regularly to try to substitute it with protein from plant or dairy sources, at least occasionally, he said. When doing so, “clinicians should ask their patients’ preferences before assuming that they will do everything that you ask them to do because nutrition in cirrhosis is really critical — not only what they eat but also when they eat. Working with a dietitian, like we did in our study, is critical, or at least having access to one if you don’t have one in your practice.”
Positive Results From a Simple Change
Commenting on the study, Nancy S. Reau, MD, section chief, hepatology and associate director of organ transplantation at Rush Medical College in Chicago, said, “My biggest concern is making sure patients are ingesting enough quality protein and calories because anorexia is a common complication in cirrhosis, and sarcopenia is associated with poor outcomes.
“You don’t want to suggest a change that will result in eating less or skipping a meal,” she said. So, “it is encouraging to see that suggesting a small change, just one meal a day, that may not impact calorie intake could have positive results.”
Dr. Reau added that “it is great to see evidence that this small change also could be a way of decreasing the risk of HE while not compromising on patient nutrition.”
Larger studies with outcome data showing that this approach could prevent readmission in patients hospitalized for HE would be helpful, she said.
The study was partly supported by the ACG Clinical Research Award, VA Merit Review 2I01CX001076, I01CX002472, and NIAAA RO1AA29398. Dr. Bajaj and Dr. Reau reported no conflicts of interest.
A version of this article appeared on Medscape.com.
Are Direct-to-Consumer Microbiome Tests Clinically Useful?
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
Companies selling gut microbiome tests directly to consumers offer up a variety of claims to promote their products.
“We analyze the trillions of microbes in your gut microflora and craft a unique formula for your unique gut needs,” one says. “Get actionable dietary, supplement, and lifestyle recommendations from our microbiome experts based on your results, tailored to mom and baby’s biomarkers. ... Any family member like dads or siblings are welcome too,” says another.
The companies assert that they can improve gut health by offering individuals personalized treatments based on their gut microbiome test results. The trouble is, no provider, company, or technology can reliably do that yet.
Clinical Implications, Not Applications
The microbiome is the “constellation of microorganisms that call the human body home,” including many strains of bacteria, fungi, and viruses. That constellation comprises some 39 trillion cells.
Although knowledge is increasing on the oral, cutaneous, and vaginal microbiomes, the gut microbiome is arguably the most studied. However, while research is increasingly demonstrating that the gut microbiome has clinical implications, much work needs to be done before reliable applications based on that research are available.
But , Erik C. von Rosenvinge, MD, AGAF, a professor at the University of Maryland School of Medicine and chief of gastroenterology at the VA Maryland Health Care System, Baltimore, said in an interview.
“If you go to their websites, even if it’s not stated overtly, these companies at least give the impression that they’re providing actionable, useful information,” he said. “The sites recommend microbiome testing, and often supplements, probiotics, or other products that they sell. And consumers are told they need to be tested again once they start taking any of these products to see if they’re receiving any benefit.”
Dr. von Rosenvinge and colleagues authored a recent article in Science arguing that DTC microbiome tests “lack analytical and clinical validity” — and yet regulation of the industry has been “generally ignored.” They identified 31 companies globally, 17 of which are based in the United States, claiming to have products and/or services aimed at changing the intestinal microbiome.
Unreliable, Unregulated
The lack of reliability has been shown by experts who have tested the tests.
“People have taken the same stool sample, sent it to multiple companies, and gotten different results back,” Dr. von Rosenvinge said. “People also have taken a stool sample and sent it to the same company under two different names and received two different results. If the test is unreliable at its foundational level, it’s hard to use it in any clinical way.”
Test users’ methods and the companies’ procedures can affect the results, Dina Kao, MD, a professor at the University of Alberta, Edmonton, Alberta, Canada, said in an interview.
“So many biases can be introduced at every single step of the way, starting from how the stool sample was collected and how it’s preserved or not being preserved, because that can introduce a lot of noise that would change the analyses. Which primer they’re using to amplify the signals and which bioinformatic pipeline they use are also important,” said Dr. Kao, who presented at the recent Gut Microbiota for Health World Summit, organized by the American Gastroenterological Association (AGA) and the European Society of Neurogastroenterology and Motility (ESNM).
Different investigators and companies use different technologies, so it’s very difficult to compare them and to create a standard, said Mahmoud Ghannoum, PhD, a professor in the dermatology and pathology departments at Case Western Reserve University School of Medicine and director of the Center for Medical Mycology at University Hospitals in Cleveland.
The complexity of the gut microbiome makes test standardization more difficult than it is when just one organism is involved, Dr. Ghannoum, who chaired the antifungal subcommittee at the Clinical and Laboratory Standards Institute, said in an interview.
“Even though many researchers are focusing on bacteria, we also have fungi and viruses. We need standardization of methods for testing these organisms if we want to have regulations,” said Dr. Ghannoum, a cofounder of BIOHM, a microbiome company that offers nondiagnostic tests and markets a variety of probiotics, prebiotics, and immunity supplements. BIOHM is one of the 31 companies identified by Dr. von Rosenvinge and colleagues, as noted above.
Dr. Ghannoum believes that taking a systematic approach could facilitate standardization and, ultimately, regulation of the DTC microbiome testing products. He and his colleagues described such an approach by outlining the stages for designing probiotics capable of modulating the microbiome in chronic diseases, using Crohn’s disease as a model. Their strategy involved the following steps:
- Using primary microbiome data to identify, by abundance, the microorganisms underlying dysbiosis.
- Gaining insight into the interactions among the identified pathogens.
- Conducting a correlation analysis to identify potential lead probiotic strains that antagonize these pathogens and discovering metabolites that can interrupt their interactions.
- Creating a prototype formulation for testing.
- Validating the efficacy of the candidate formulation via preclinical in vitro and in vivo testing.
- Conducting clinical testing.
Dr. Ghannoum recommends that companies use a similar process “to provide evidence that what they are doing will be helpful, not only for them but also for the reputation of the whole industry.”
Potential Pitfalls
Whether test results from commercial companies are positioned as wellness aids or diagnostic tools, providing advice based on the results “is where the danger can really come in,” Dr. Kao said. “There is still so much we don’t know about which microbial signatures are associated with each condition.”
“Even when we have a solution, like the Crohn’s exclusion diet, a physician doesn’t know enough of the nuances to give advice to a patient,” she said. “That really should be done under the guidance of an expert dietitian. And if a company is selling probiotics, I personally feel that’s not ethical. I’m pretty sure there’s always going to be some kind of conflict of interest.”
Supplements and probiotics are generally safe, but negative consequences can occur, Dr. von Rosenvinge noted.
“We occasionally see people who end up with liver problems as a result of certain supplements, and rarely, probiotics have been associated with infections from those organisms, usually in those with a compromised immune system,” he said.
Other risks include people taking supplements or probiotics when they actually have a medically treatable condition or delays in diagnosis of a potentially serious underlying condition, such as colon cancer, he said. Some patients may stop taking their traditional medication in favor of taking supplements or may experience a drug-supplement interaction if they take both.
What to Tell Patients
“Doctors should be advising against this testing for their patients,” gastroenterologist Colleen R. Kelly, MD, AGAF, Brigham and Women’s Hospital, Boston, said in an interview. “I explain to patients that these tests are not validated and are clinically meaningless data and not worth the money. There is a reason they are not covered by insurance.
“Recommendations to purchase probiotics or supplements manufactured by the testing company to ‘restore a balanced or healthy microbiome’ clearly seem like a scam,” she added. “I believe some of these companies are capitalizing on patients who are desperate for answers to explain chronic symptoms, such as bloating in irritable bowel syndrome.”
Dr. von Rosenvinge said that the message to patients “is that the science isn’t there yet to support using the results of these tests in a meaningful way. We believe the microbiome is very important in health and disease, but the tests themselves in their current state are not as reliable and reproducible as we would like.”
When patients come in with test results, the first question a clinician should ask is what led them to seek out this type of information in the first place, Dr. von Rosenvinge said.
“Our patient focus groups suggested that many have not gotten clear, satisfactory answers from traditional medicine,” he said. “We don’t have a single test that says, yes, you have irritable bowel syndrome, or no, you don’t. We might suggest things that are helpful for some people and are less helpful for others.”
Dr. Kelly said she worries that “there are snake oil salesmen and cons out there who will gladly take your money. These may be smart people, capable of doing very high-level testing, and even producing very detailed and accurate results, but that doesn’t mean we know what to do with them.”
She hopes to see a microbiome-based diagnostic test in the future, particularly if the ability to therapeutically manipulate the gut microbiome in various diseases becomes a reality.
Educate Clinicians, Companies
More education is needed on the subject, so we can become “microbial clinicians,” Dr. Kao said.
“The microbiome never came up when I was going through my medical education,” she said. But we, and the next generation of physicians, “need to at least be able to understand the basics.
“Hopefully, one day, we will be in a position where we can have meaningful interpretations of the test results and make some kind of meaningful dietary interventions,” Dr. Kao added.
As for clinicians who are currently ordering these tests and products directly from the DTC companies, Dr. Kao said, “I roll my eyes.”
Dr. Ghannoum reiterated that companies offering microbiome tests and products also need to be educated and encouraged to use systematic approaches to product development and interpretation.
“Companies should be open to calls from clinicians and be ready to explain findings on a report, as well as the basis for any recommendations,” he said.
Dr. von Rosenvinge, Dr. Kao, and Dr. Kelly had no relevant conflicts of interest. Dr. Ghannoum is a cofounder of BIOHM.
A version of this article appeared on Medscape.com.
Gut Bacteria’s Influence on Obesity Differs in Men and Women
Gut bacteria predictive of body mass index (BMI), waist circumference, and fat mass are different in men and women, and therefore, interventions to prevent obesity may need to be different, as well, new research suggested.
Metagenomic analyses of fecal samples and metabolomic analyses of serum samples from 361 volunteers in Spain showed that an imbalance in specific bacterial strains likely play an important role in the onset and development of obesity, and that there are “considerable differences” between the sexes, said lead study author Paula Aranaz, MD, Centre for Nutrition Research, at the University of Navarra, Pamplona, Spain.
“We are still far from knowing the magnitude of the effect that the microbiota [bacteria, viruses, fungi, and protozoa] has on our metabolic health and, therefore, on the greater or lesser risk of suffering from obesity,” Dr. Aranaz told this news organization.
“However,” she said, “what does seem clear is that the microorganisms of our intestine perform a crucial role in the way we metabolize nutrients and, therefore, influence the compounds and molecules that circulate through our body, affecting different organs and tissues, and our general metabolic health.”
The study will be presented at the European Congress on Obesity (ECO) 2024, to be held in Venice, Italy, from May 12 to 15. The abstract is now available online.
Variation in Bacteria Species, Abundance
The researchers examined the fecal metabolome of 361 adult volunteers (median age, 44; 70%, women) from the Spanish Obekit randomized trial, which investigated the relationship between genetic variants and how participants responded to a low-calorie diet.
A total of 65 participants were normal weight, 110 with overweight, and 186 with obesity. They were matched for sex and age and classified according to an obesity (OB) index as LOW or HIGH.
LOW included those with a BMI ≤ 30 kg/m2, fat mass percentage ≤ 25% (women) or ≤ 32% (men), and waist circumference ≤ 88 cm (women) or ≤ 102 cm (men). HIGH included those with a BMI > 30 kg/m2, fat mass > 25% (women) or > 32% (men), and waist circumference > 88 cm (women) or > 102 cm (men).
In men, a greater abundance of Parabacteroides helcogenes and Campylobacter canadensis species was associated with higher BMI, fat mass, and waist circumference.
By contrast, in women, a greater abundance of Prevotella micans, P brevis, and P sacharolitica was predictive of higher BMI, fat mass, and waist circumference.
Untargeted metabolomic analyses revealed variation in the abundance of certain metabolites in participants with a HIGH OB index — notably, higher levels of phospholipids (implicated in the development of metabolic disease and modulators of insulin sensitivity) and sphingolipids, which play a role in the development of diabetes and the emergence of vascular complications.
“We can reduce the risk of metabolic diseases by modulating the gut microbiome through nutritional and lifestyle factors, including dietary patterns, foods, exercise, probiotics, and postbiotics,” Dr. Aranaz said. Which modifications can and should be made “depend on many factors, including the host genetics, endocrine system, sex, and age.”
The researchers currently are working to try to relate the identified metabolites to the bacterial species that could be producing them and to characterize the biological effect that these species and their metabolites exert on the organism, Dr. Aranaz added.
Ultimately, she said, “we would like to [design] a microbiota/metabolomic test that can be used in clinical practice to identify human enterotypes and to personalize the dietary strategies to minimize the health risks related to gut dysbiosis.”
No funding was reported. Dr. Aranaz declared no conflicts of interest.
A version of this article appeared on Medscape.com .
Gut bacteria predictive of body mass index (BMI), waist circumference, and fat mass are different in men and women, and therefore, interventions to prevent obesity may need to be different, as well, new research suggested.
Metagenomic analyses of fecal samples and metabolomic analyses of serum samples from 361 volunteers in Spain showed that an imbalance in specific bacterial strains likely play an important role in the onset and development of obesity, and that there are “considerable differences” between the sexes, said lead study author Paula Aranaz, MD, Centre for Nutrition Research, at the University of Navarra, Pamplona, Spain.
“We are still far from knowing the magnitude of the effect that the microbiota [bacteria, viruses, fungi, and protozoa] has on our metabolic health and, therefore, on the greater or lesser risk of suffering from obesity,” Dr. Aranaz told this news organization.
“However,” she said, “what does seem clear is that the microorganisms of our intestine perform a crucial role in the way we metabolize nutrients and, therefore, influence the compounds and molecules that circulate through our body, affecting different organs and tissues, and our general metabolic health.”
The study will be presented at the European Congress on Obesity (ECO) 2024, to be held in Venice, Italy, from May 12 to 15. The abstract is now available online.
Variation in Bacteria Species, Abundance
The researchers examined the fecal metabolome of 361 adult volunteers (median age, 44; 70%, women) from the Spanish Obekit randomized trial, which investigated the relationship between genetic variants and how participants responded to a low-calorie diet.
A total of 65 participants were normal weight, 110 with overweight, and 186 with obesity. They were matched for sex and age and classified according to an obesity (OB) index as LOW or HIGH.
LOW included those with a BMI ≤ 30 kg/m2, fat mass percentage ≤ 25% (women) or ≤ 32% (men), and waist circumference ≤ 88 cm (women) or ≤ 102 cm (men). HIGH included those with a BMI > 30 kg/m2, fat mass > 25% (women) or > 32% (men), and waist circumference > 88 cm (women) or > 102 cm (men).
In men, a greater abundance of Parabacteroides helcogenes and Campylobacter canadensis species was associated with higher BMI, fat mass, and waist circumference.
By contrast, in women, a greater abundance of Prevotella micans, P brevis, and P sacharolitica was predictive of higher BMI, fat mass, and waist circumference.
Untargeted metabolomic analyses revealed variation in the abundance of certain metabolites in participants with a HIGH OB index — notably, higher levels of phospholipids (implicated in the development of metabolic disease and modulators of insulin sensitivity) and sphingolipids, which play a role in the development of diabetes and the emergence of vascular complications.
“We can reduce the risk of metabolic diseases by modulating the gut microbiome through nutritional and lifestyle factors, including dietary patterns, foods, exercise, probiotics, and postbiotics,” Dr. Aranaz said. Which modifications can and should be made “depend on many factors, including the host genetics, endocrine system, sex, and age.”
The researchers currently are working to try to relate the identified metabolites to the bacterial species that could be producing them and to characterize the biological effect that these species and their metabolites exert on the organism, Dr. Aranaz added.
Ultimately, she said, “we would like to [design] a microbiota/metabolomic test that can be used in clinical practice to identify human enterotypes and to personalize the dietary strategies to minimize the health risks related to gut dysbiosis.”
No funding was reported. Dr. Aranaz declared no conflicts of interest.
A version of this article appeared on Medscape.com .
Gut bacteria predictive of body mass index (BMI), waist circumference, and fat mass are different in men and women, and therefore, interventions to prevent obesity may need to be different, as well, new research suggested.
Metagenomic analyses of fecal samples and metabolomic analyses of serum samples from 361 volunteers in Spain showed that an imbalance in specific bacterial strains likely play an important role in the onset and development of obesity, and that there are “considerable differences” between the sexes, said lead study author Paula Aranaz, MD, Centre for Nutrition Research, at the University of Navarra, Pamplona, Spain.
“We are still far from knowing the magnitude of the effect that the microbiota [bacteria, viruses, fungi, and protozoa] has on our metabolic health and, therefore, on the greater or lesser risk of suffering from obesity,” Dr. Aranaz told this news organization.
“However,” she said, “what does seem clear is that the microorganisms of our intestine perform a crucial role in the way we metabolize nutrients and, therefore, influence the compounds and molecules that circulate through our body, affecting different organs and tissues, and our general metabolic health.”
The study will be presented at the European Congress on Obesity (ECO) 2024, to be held in Venice, Italy, from May 12 to 15. The abstract is now available online.
Variation in Bacteria Species, Abundance
The researchers examined the fecal metabolome of 361 adult volunteers (median age, 44; 70%, women) from the Spanish Obekit randomized trial, which investigated the relationship between genetic variants and how participants responded to a low-calorie diet.
A total of 65 participants were normal weight, 110 with overweight, and 186 with obesity. They were matched for sex and age and classified according to an obesity (OB) index as LOW or HIGH.
LOW included those with a BMI ≤ 30 kg/m2, fat mass percentage ≤ 25% (women) or ≤ 32% (men), and waist circumference ≤ 88 cm (women) or ≤ 102 cm (men). HIGH included those with a BMI > 30 kg/m2, fat mass > 25% (women) or > 32% (men), and waist circumference > 88 cm (women) or > 102 cm (men).
In men, a greater abundance of Parabacteroides helcogenes and Campylobacter canadensis species was associated with higher BMI, fat mass, and waist circumference.
By contrast, in women, a greater abundance of Prevotella micans, P brevis, and P sacharolitica was predictive of higher BMI, fat mass, and waist circumference.
Untargeted metabolomic analyses revealed variation in the abundance of certain metabolites in participants with a HIGH OB index — notably, higher levels of phospholipids (implicated in the development of metabolic disease and modulators of insulin sensitivity) and sphingolipids, which play a role in the development of diabetes and the emergence of vascular complications.
“We can reduce the risk of metabolic diseases by modulating the gut microbiome through nutritional and lifestyle factors, including dietary patterns, foods, exercise, probiotics, and postbiotics,” Dr. Aranaz said. Which modifications can and should be made “depend on many factors, including the host genetics, endocrine system, sex, and age.”
The researchers currently are working to try to relate the identified metabolites to the bacterial species that could be producing them and to characterize the biological effect that these species and their metabolites exert on the organism, Dr. Aranaz added.
Ultimately, she said, “we would like to [design] a microbiota/metabolomic test that can be used in clinical practice to identify human enterotypes and to personalize the dietary strategies to minimize the health risks related to gut dysbiosis.”
No funding was reported. Dr. Aranaz declared no conflicts of interest.
A version of this article appeared on Medscape.com .
Genetic Testing of Some Patients With Early-Onset AF Advised
Genetic testing may be considered in patients with early-onset atrial fibrillation (AF), particularly those with a positive family history and lack of conventional clinical risk factors, because specific genetic variants may underlie AF as well as “potentially more sinister cardiac conditions,” a new white paper from the Canadian Cardiovascular Society suggested.
“Given the resources and logistical challenges potentially imposed by genetic testing (that is, the majority of cardiology and arrhythmia clinics are not presently equipped to offer it), we have not recommended routine genetic testing for early-onset AF patients at this time,” lead author Jason D. Roberts, MD, associate professor of medicine at McMaster University in Hamilton, Ontario, Canada, told this news organization.
“We do, however, recommend that early-onset AF patients undergo clinical screening for potential coexistence of a ventricular arrhythmia or cardiomyopathy syndrome through careful history, including family history, and physical examination, along with standard clinical testing, including ECG, echocardiogram, and Holter monitoring,” he said.
The white paper was published online in the Canadian Journal of Cardiology.
Routine Testing Unwarranted
The Canadian Cardiovascular Society reviewed AF research in 2022 and concluded that a guideline update was not yet warranted. One area meriting consideration but lacking sufficient evidence for a formal guideline was the clinical application of AF genetics.
Therefore, the society formed a writing group to assess the evidence linking genetic factors to AF, discuss an approach to using genetic testing for early-onset patients with AF, and consider the potential value of genetic testing in the foreseeable future.
The resulting white paper reviews familial and epidemiologic evidence for a genetic contribution to AF. As an example, the authors pointed to work from the Framingham Heart Study showing a statistically significant risk for AF among first-degree relatives of patients with AF. The overall odds ratio (OR) for AF among first-degree relatives was 1.85. But for first-degree relatives of patients with AF onset at younger than age 75 years, the OR increased to 3.23.
Other evidence included the identification of two rare genetic variants: KCNQ1 in a Chinese family and NPPA in a family with Northern European ancestry. In case-control studies, a single gene, titin (TTN), was linked to an increased burden of loss-of-function variants in patients with AF compared with controls. The variant was associated with a 2.2-fold increased risk for AF.
For example, loss-of-function SCN5A variants are implicated in Brugada syndrome and cardiac conduction system disease, whereas gain-of-function variants cause long QT syndrome type 3 and multifocal ectopic Purkinje-related premature contractions. Each of these conditions was associated with an increased prevalence of AF.
Similarly, genes implicated in various other forms of ventricular channelopathies also have been implicated in AF, as have ion channels primarily expressed in the atria and not the ventricles, such as KCNA5 and GJA5.
Nevertheless, in most cases, AF is diagnosed in the context of older age and established cardiovascular risk factors, according to the authors. The contribution of genetic factors in this population is relatively low, highlighting the limited role for genetic testing when AF develops in the presence of multiple conventional clinical risk factors.
Cardiogenetic Expertise Required
“Although significant progress has been made, additional work is needed before [beginning] routine integration of clinical genetic testing for early-onset AF patients,” Dr. Roberts said. The ideal clinical genetic testing panel for AF is still unclear, and the inclusion of genes for which there is no strong evidence of involvement in AF “creates the potential for harm.”
Specifically, “a genetic variant could be incorrectly assigned as the cause of AF, which could create confusion for the patient and family members and lead to inappropriate clinical management,” said Dr. Roberts.
“Beyond cost, routine introduction of genetic testing for AF patients will require allocation of significant resources, given that interpretation of genetic testing results can be nuanced,” he noted. “This nuance is anticipated to be heightened in AF, given that many genetic variants have low-to-intermediate penetrance and can manifest with variable clinical phenotypes.”
“Traditionally, genetic testing has been performed and interpreted, and results communicated, by dedicated cardiogenetic clinics with specialized expertise,” he added. “Existing cardiogenetic clinics, however, are unlikely to be sufficient in number to accommodate the large volume of AF patients that may be eligible for testing.”
Careful Counseling
Jim W. Cheung, MD, chair of the American College of Cardiology Electrophysiology Council, told this news organization that the white paper is consistent with the latest European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement published in 2022.
Overall, the approach suggested for genetic testing “is a sound one, but one that requires implementation by clinicians with access to cardiogenetic expertise,” said Cheung, who was not involved in the study. “Any patient undergoing genetic testing needs to be carefully counseled about the potential uncertainties associated with the actual test results and their implications on clinical management.”
Variants of uncertain significance that are detected with genetic testing “can be a source of stress for clinicians and patients,” he said. “Therefore, patient education prior to and after genetic testing is essential.”
Furthermore, he said, “in many patients with early-onset AF who harbor pathogenic variants, initial imaging studies may not detect any signs of cardiomyopathy. In these patients, regular follow-up to assess for development of cardiomyopathy in the future is necessary.”
The white paper was drafted without outside funding. Dr. Roberts and Dr. Cheung reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Genetic testing may be considered in patients with early-onset atrial fibrillation (AF), particularly those with a positive family history and lack of conventional clinical risk factors, because specific genetic variants may underlie AF as well as “potentially more sinister cardiac conditions,” a new white paper from the Canadian Cardiovascular Society suggested.
“Given the resources and logistical challenges potentially imposed by genetic testing (that is, the majority of cardiology and arrhythmia clinics are not presently equipped to offer it), we have not recommended routine genetic testing for early-onset AF patients at this time,” lead author Jason D. Roberts, MD, associate professor of medicine at McMaster University in Hamilton, Ontario, Canada, told this news organization.
“We do, however, recommend that early-onset AF patients undergo clinical screening for potential coexistence of a ventricular arrhythmia or cardiomyopathy syndrome through careful history, including family history, and physical examination, along with standard clinical testing, including ECG, echocardiogram, and Holter monitoring,” he said.
The white paper was published online in the Canadian Journal of Cardiology.
Routine Testing Unwarranted
The Canadian Cardiovascular Society reviewed AF research in 2022 and concluded that a guideline update was not yet warranted. One area meriting consideration but lacking sufficient evidence for a formal guideline was the clinical application of AF genetics.
Therefore, the society formed a writing group to assess the evidence linking genetic factors to AF, discuss an approach to using genetic testing for early-onset patients with AF, and consider the potential value of genetic testing in the foreseeable future.
The resulting white paper reviews familial and epidemiologic evidence for a genetic contribution to AF. As an example, the authors pointed to work from the Framingham Heart Study showing a statistically significant risk for AF among first-degree relatives of patients with AF. The overall odds ratio (OR) for AF among first-degree relatives was 1.85. But for first-degree relatives of patients with AF onset at younger than age 75 years, the OR increased to 3.23.
Other evidence included the identification of two rare genetic variants: KCNQ1 in a Chinese family and NPPA in a family with Northern European ancestry. In case-control studies, a single gene, titin (TTN), was linked to an increased burden of loss-of-function variants in patients with AF compared with controls. The variant was associated with a 2.2-fold increased risk for AF.
For example, loss-of-function SCN5A variants are implicated in Brugada syndrome and cardiac conduction system disease, whereas gain-of-function variants cause long QT syndrome type 3 and multifocal ectopic Purkinje-related premature contractions. Each of these conditions was associated with an increased prevalence of AF.
Similarly, genes implicated in various other forms of ventricular channelopathies also have been implicated in AF, as have ion channels primarily expressed in the atria and not the ventricles, such as KCNA5 and GJA5.
Nevertheless, in most cases, AF is diagnosed in the context of older age and established cardiovascular risk factors, according to the authors. The contribution of genetic factors in this population is relatively low, highlighting the limited role for genetic testing when AF develops in the presence of multiple conventional clinical risk factors.
Cardiogenetic Expertise Required
“Although significant progress has been made, additional work is needed before [beginning] routine integration of clinical genetic testing for early-onset AF patients,” Dr. Roberts said. The ideal clinical genetic testing panel for AF is still unclear, and the inclusion of genes for which there is no strong evidence of involvement in AF “creates the potential for harm.”
Specifically, “a genetic variant could be incorrectly assigned as the cause of AF, which could create confusion for the patient and family members and lead to inappropriate clinical management,” said Dr. Roberts.
“Beyond cost, routine introduction of genetic testing for AF patients will require allocation of significant resources, given that interpretation of genetic testing results can be nuanced,” he noted. “This nuance is anticipated to be heightened in AF, given that many genetic variants have low-to-intermediate penetrance and can manifest with variable clinical phenotypes.”
“Traditionally, genetic testing has been performed and interpreted, and results communicated, by dedicated cardiogenetic clinics with specialized expertise,” he added. “Existing cardiogenetic clinics, however, are unlikely to be sufficient in number to accommodate the large volume of AF patients that may be eligible for testing.”
Careful Counseling
Jim W. Cheung, MD, chair of the American College of Cardiology Electrophysiology Council, told this news organization that the white paper is consistent with the latest European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement published in 2022.
Overall, the approach suggested for genetic testing “is a sound one, but one that requires implementation by clinicians with access to cardiogenetic expertise,” said Cheung, who was not involved in the study. “Any patient undergoing genetic testing needs to be carefully counseled about the potential uncertainties associated with the actual test results and their implications on clinical management.”
Variants of uncertain significance that are detected with genetic testing “can be a source of stress for clinicians and patients,” he said. “Therefore, patient education prior to and after genetic testing is essential.”
Furthermore, he said, “in many patients with early-onset AF who harbor pathogenic variants, initial imaging studies may not detect any signs of cardiomyopathy. In these patients, regular follow-up to assess for development of cardiomyopathy in the future is necessary.”
The white paper was drafted without outside funding. Dr. Roberts and Dr. Cheung reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Genetic testing may be considered in patients with early-onset atrial fibrillation (AF), particularly those with a positive family history and lack of conventional clinical risk factors, because specific genetic variants may underlie AF as well as “potentially more sinister cardiac conditions,” a new white paper from the Canadian Cardiovascular Society suggested.
“Given the resources and logistical challenges potentially imposed by genetic testing (that is, the majority of cardiology and arrhythmia clinics are not presently equipped to offer it), we have not recommended routine genetic testing for early-onset AF patients at this time,” lead author Jason D. Roberts, MD, associate professor of medicine at McMaster University in Hamilton, Ontario, Canada, told this news organization.
“We do, however, recommend that early-onset AF patients undergo clinical screening for potential coexistence of a ventricular arrhythmia or cardiomyopathy syndrome through careful history, including family history, and physical examination, along with standard clinical testing, including ECG, echocardiogram, and Holter monitoring,” he said.
The white paper was published online in the Canadian Journal of Cardiology.
Routine Testing Unwarranted
The Canadian Cardiovascular Society reviewed AF research in 2022 and concluded that a guideline update was not yet warranted. One area meriting consideration but lacking sufficient evidence for a formal guideline was the clinical application of AF genetics.
Therefore, the society formed a writing group to assess the evidence linking genetic factors to AF, discuss an approach to using genetic testing for early-onset patients with AF, and consider the potential value of genetic testing in the foreseeable future.
The resulting white paper reviews familial and epidemiologic evidence for a genetic contribution to AF. As an example, the authors pointed to work from the Framingham Heart Study showing a statistically significant risk for AF among first-degree relatives of patients with AF. The overall odds ratio (OR) for AF among first-degree relatives was 1.85. But for first-degree relatives of patients with AF onset at younger than age 75 years, the OR increased to 3.23.
Other evidence included the identification of two rare genetic variants: KCNQ1 in a Chinese family and NPPA in a family with Northern European ancestry. In case-control studies, a single gene, titin (TTN), was linked to an increased burden of loss-of-function variants in patients with AF compared with controls. The variant was associated with a 2.2-fold increased risk for AF.
For example, loss-of-function SCN5A variants are implicated in Brugada syndrome and cardiac conduction system disease, whereas gain-of-function variants cause long QT syndrome type 3 and multifocal ectopic Purkinje-related premature contractions. Each of these conditions was associated with an increased prevalence of AF.
Similarly, genes implicated in various other forms of ventricular channelopathies also have been implicated in AF, as have ion channels primarily expressed in the atria and not the ventricles, such as KCNA5 and GJA5.
Nevertheless, in most cases, AF is diagnosed in the context of older age and established cardiovascular risk factors, according to the authors. The contribution of genetic factors in this population is relatively low, highlighting the limited role for genetic testing when AF develops in the presence of multiple conventional clinical risk factors.
Cardiogenetic Expertise Required
“Although significant progress has been made, additional work is needed before [beginning] routine integration of clinical genetic testing for early-onset AF patients,” Dr. Roberts said. The ideal clinical genetic testing panel for AF is still unclear, and the inclusion of genes for which there is no strong evidence of involvement in AF “creates the potential for harm.”
Specifically, “a genetic variant could be incorrectly assigned as the cause of AF, which could create confusion for the patient and family members and lead to inappropriate clinical management,” said Dr. Roberts.
“Beyond cost, routine introduction of genetic testing for AF patients will require allocation of significant resources, given that interpretation of genetic testing results can be nuanced,” he noted. “This nuance is anticipated to be heightened in AF, given that many genetic variants have low-to-intermediate penetrance and can manifest with variable clinical phenotypes.”
“Traditionally, genetic testing has been performed and interpreted, and results communicated, by dedicated cardiogenetic clinics with specialized expertise,” he added. “Existing cardiogenetic clinics, however, are unlikely to be sufficient in number to accommodate the large volume of AF patients that may be eligible for testing.”
Careful Counseling
Jim W. Cheung, MD, chair of the American College of Cardiology Electrophysiology Council, told this news organization that the white paper is consistent with the latest European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement published in 2022.
Overall, the approach suggested for genetic testing “is a sound one, but one that requires implementation by clinicians with access to cardiogenetic expertise,” said Cheung, who was not involved in the study. “Any patient undergoing genetic testing needs to be carefully counseled about the potential uncertainties associated with the actual test results and their implications on clinical management.”
Variants of uncertain significance that are detected with genetic testing “can be a source of stress for clinicians and patients,” he said. “Therefore, patient education prior to and after genetic testing is essential.”
Furthermore, he said, “in many patients with early-onset AF who harbor pathogenic variants, initial imaging studies may not detect any signs of cardiomyopathy. In these patients, regular follow-up to assess for development of cardiomyopathy in the future is necessary.”
The white paper was drafted without outside funding. Dr. Roberts and Dr. Cheung reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM THE CANADIAN JOURNAL OF CARDIOLOGY
Semaglutide Curbs MASLD Severity in People Living With HIV
Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.
Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
‘A First’
SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.
The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.
Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.
The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.
A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.
In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.
Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.
The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.
Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.
The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.
All participants completed the full 24 weeks of therapy at the originally prescribed dose.
Potential Impact
“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”
“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.
The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.
Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
‘A First’
SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.
The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.
Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.
The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.
A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.
In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.
Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.
The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.
Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.
The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.
All participants completed the full 24 weeks of therapy at the originally prescribed dose.
Potential Impact
“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”
“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.
The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
Semaglutide improved metabolic dysfunction–associated steatotic liver disease (MASLD) among people living with HIV, and in some cases resolved it completely, according to results from the SLIM LIVER study presented by the AIDS Clinical Trials Group (ACTG) at this year’s Conference on Retroviruses and Opportunistic Infections (CROI) 2024 Annual Meeting in Denver.
Furthermore, although muscle volume decreased with weight loss, participants did not experience significant changes in muscle quality or physical function.
‘A First’
SLIM LIVER is the first study evaluating semaglutide as a treatment of MASLD among people living with HIV.
The phase 2b, single-arm pilot study enrolled adults living with HIV who were virally suppressed and had central adiposity, insulin resistance or prediabetes, and steatotic liver disease.
Participants self-injected semaglutide weekly at increasing doses until they reached a 1-mg dose at week 4. At 24 weeks, the study team assessed changes in participants’ intra-hepatic triglyceride content using magnetic resonance imaging-proton density fat fraction.
The primary analysis results from SLIM LIVER were reported in an oral presentation, “Semaglutide Reduces Metabolic-Associated Steatotic Liver Disease in People With HIV: The SLIM LIVER Study,” on March 5 by Jordan E. Lake, MD, MSc, of UTHealth Houston.
A subgroup analysis of the study was provided in a poster, “Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study,” presented on March 4 by Grace L. Ditzenberger, PT, DPT, of the University of Colorado Anschutz Medical Campus in Aurora.
In the primary analysis, the median age of the 49 participants was 52 years, 43% were women (cisgender and transgender), the mean body mass index was 35, 39% were Hispanic and 33% were Black/African American, and 82% were taking antiretroviral therapy that included an integrase inhibitor.
Liver fat was reduced by an average of 31%, with 29% of participants experiencing a complete resolution (5% or less liver fat) of MASLD. They also experienced weight loss, reduced fasting blood glucose, and reduced fasting triglycerides, consistent with effects observed in studies of semaglutide in people without HIV.
The sub-analysis of the 46 participants for whom muscle measurements were available showed that muscle volume (measured in the psoas) decreased but with no significant change in physical function.
Semaglutide was generally well tolerated, with an adverse event profile similar to that seen in individuals without HIV.
The most common adverse events were gastrointestinal (ie, nausea, diarrhea, vomiting, and abdominal pain). Two participants experienced more significant adverse events possibly related to semaglutide but were able to continue in the study.
All participants completed the full 24 weeks of therapy at the originally prescribed dose.
Potential Impact
“Even at the low dose of 1 mg every week, most participants lost significant weight, and weight loss was closely associated with improvements in MASLD,” Dr. Lake said. “Additional research will assess the secondary effects of semaglutide on systemic inflammation and metabolism and determine whether semaglutide may have unique risks or benefits for people living with HIV.”
“These findings have the potential to have a significant impact on the health and quality of life of people living with HIV,” added ACTG Chair Judith Currier, MD, MSc, University of California Los Angeles.
The SLIM LIVER study was sponsored by the US National Institute of Allergy and Infectious Diseases (NIAID), with additional funding from UTHealth Houston McGovern School of Medicine. ACTG is a clinical trials network focused on HIV and other infectious diseases, funded by NIAID and collaborating institutes of the US National Institutes of Health.
No conflicts of interest were reported.
A version of this article appeared on Medscape.com.
FROM CROI 2024
Higher Dietary Niacin Tied to Lower Mortality Risk in MASLD
TOPLINE:
Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.
METHODOLOGY:
- Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
- Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
- Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.
TAKEAWAY:
- During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
- Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
- For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
- When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
- An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.
IN PRACTICE:
“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.
SOURCE:
The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.
LIMITATIONS:
Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.
DISCLOSURES:
One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.
METHODOLOGY:
- Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
- Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
- Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.
TAKEAWAY:
- During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
- Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
- For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
- When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
- An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.
IN PRACTICE:
“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.
SOURCE:
The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.
LIMITATIONS:
Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.
DISCLOSURES:
One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.
A version of this article appeared on Medscape.com.
TOPLINE:
Higher dietary niacin intake is associated with a lower risk for all-cause mortality among people with metabolic dysfunction-associated steatotic liver disease (MASLD), but there is no connection between niacin consumption and cardiovascular disease (CVD) mortality, a recent study suggested.
METHODOLOGY:
- Researchers analyzed data from the National Health and Nutrition Examination Survey (2003-2018) for 4315 adults with MASLD (mean age, 52.5 years; 55%, men; 67%, non-Hispanic White).
- Dietary niacin intake levels were based on two 24-hour dietary recall interviews to report the types and quantities of foods that participants consumed in the 24 hours prior to the interviews.
- Participants were categorized by tertile of dietary niacin intake: Tertile 1 (n = 1440), < 18.4 mg; tertile 2 (n = 1441), 18.5-26.6 mg; and tertile 3 (n = 1434), > 26.7 mg.
TAKEAWAY:
- During a median follow-up of 8.8 years, 566 deaths occurred, of which 197 were attributed to CVD.
- Compared with participants with a niacin intake of 18.4 mg or lower (the lowest tertile), the multivariable-adjusted hazard ratios (HRs) for participants with a niacin intake of 26.7 mg or higher (the highest tertile) were 0.70 for all-cause mortality and 0.65 for CVD mortality.
- For the subgroup with diabetes compared with the reference group (the first tertile), the HR of all-cause mortality in the third tertile was 0.82.
- When the subgroup without diabetes was compared with the reference group, the HR of all-cause mortality in the third tertile was 0.58, suggesting a significant interaction between niacin and diabetes with the risk of all-cause mortality.
- An inverse association between dietary niacin intake and all-cause mortality was seen in sensitivity analyses, when excluding a participant who died within 2 years of follow-up.
IN PRACTICE:
“Higher dietary niacin intake was associated with a lower risk of all-cause mortality,” but not CVD, among individuals with MASLD, and “the dose-response association…needs to be further investigated to determine optimal intake level,” the authors wrote.
SOURCE:
The study, led by Jie Pan, MD, Sun Yat-sen University, Guangzhou, China, was published online in JAMA Network Open.
LIMITATIONS:
Physical activity data were missing and could not be adjusted for. The National Death Index used by the researchers has only “modest” ability to accurately classify CVD mortality, and the dietary data were subject to recall bias.
DISCLOSURES:
One author was supported by a grant from the National Nature Science Foundation of China. No other conflicts of interest were reported.
A version of this article appeared on Medscape.com.
Hypertension Stable in US, Antihypertensive Med Use Rises
TOPLINE:
Hypertension prevalence remained stable in the United States at 30% after guidelines updated in 2017 lowered the threshold for the condition, while antihypertensive medication use rose about 3%, new research from the Centers for Disease Control and Prevention (CDC) shows.
METHODOLOGY:
- Researchers analyzed data from the Behavioral Risk Factor Surveillance System, a telephone survey of US adults aged 18 years and older.
- Self-reported diagnosed hypertension was defined as an affirmative response to the question, “Have you ever been told by a doctor, nurse, or other health professional that you have high blood pressure?”
- To determine treatment, respondents who answered the first question affirmatively were then asked, “Are you currently taking medicine for your high blood pressure?”
- Hypertension and treatment were assessed by age group (18-44, 45-64, and > 65 years), sex, race, ethnicity, level of education, and state of residence.
TAKEAWAY:
- The final analytic samples for 2017, 2019, and 2021 included 425,417, 392,100, and 410,318 participants, respectively.
- From 2017 to 2021, the overall age-standardized prevalence of hypertension did not change, remaining at almost exactly 30%.
- The age-standardized prevalence of antihypertensive medication use among individuals with hypertension increased by 3.1 percentage points, from 59.8% to 62.9%.
- Increases in medication use were seen in most sociodemographic groups; for example, in 2021, the prevalence was higher among women than among men (68.5% vs 59.4%), among adults aged ≥ 65 years than among those aged 18-44 years (92.5% vs 42.5%), and among Black patients than among White patients (71.3% vs 62%).
- Increases in medication use were also seen by state; use increased in 11 states, ranging from 52.2% in Utah to 72.8% in Mississippi in 2021, and did not decrease significantly in any state.
IN PRACTICE:
“These findings can be used to increase awareness of hypertension and promote lifestyle modifications and antihypertensive medication use to optimize blood pressure control and reduce disparities in prevalence and control,” the authors wrote.
SOURCE:
The study was led by Ahlia Sekkarie, PhD, of CDC’s Division for Heart Disease and Stroke Prevention, and published online in Morbidity and Mortality Weekly Report.
LIMITATIONS:
The study had several limitations. The findings were based on self-report. Median response rates of less than 50% could lead to under- or overestimates of prevalence. Parts of the population, such as those in long-term care facilities or without a telephone, were not included in the analysis. Some demographic categories had small sample sizes; therefore, prevalence changes might not be detectable.
DISCLOSURES:
No specific funding was reported. The authors reported no potential conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Hypertension prevalence remained stable in the United States at 30% after guidelines updated in 2017 lowered the threshold for the condition, while antihypertensive medication use rose about 3%, new research from the Centers for Disease Control and Prevention (CDC) shows.
METHODOLOGY:
- Researchers analyzed data from the Behavioral Risk Factor Surveillance System, a telephone survey of US adults aged 18 years and older.
- Self-reported diagnosed hypertension was defined as an affirmative response to the question, “Have you ever been told by a doctor, nurse, or other health professional that you have high blood pressure?”
- To determine treatment, respondents who answered the first question affirmatively were then asked, “Are you currently taking medicine for your high blood pressure?”
- Hypertension and treatment were assessed by age group (18-44, 45-64, and > 65 years), sex, race, ethnicity, level of education, and state of residence.
TAKEAWAY:
- The final analytic samples for 2017, 2019, and 2021 included 425,417, 392,100, and 410,318 participants, respectively.
- From 2017 to 2021, the overall age-standardized prevalence of hypertension did not change, remaining at almost exactly 30%.
- The age-standardized prevalence of antihypertensive medication use among individuals with hypertension increased by 3.1 percentage points, from 59.8% to 62.9%.
- Increases in medication use were seen in most sociodemographic groups; for example, in 2021, the prevalence was higher among women than among men (68.5% vs 59.4%), among adults aged ≥ 65 years than among those aged 18-44 years (92.5% vs 42.5%), and among Black patients than among White patients (71.3% vs 62%).
- Increases in medication use were also seen by state; use increased in 11 states, ranging from 52.2% in Utah to 72.8% in Mississippi in 2021, and did not decrease significantly in any state.
IN PRACTICE:
“These findings can be used to increase awareness of hypertension and promote lifestyle modifications and antihypertensive medication use to optimize blood pressure control and reduce disparities in prevalence and control,” the authors wrote.
SOURCE:
The study was led by Ahlia Sekkarie, PhD, of CDC’s Division for Heart Disease and Stroke Prevention, and published online in Morbidity and Mortality Weekly Report.
LIMITATIONS:
The study had several limitations. The findings were based on self-report. Median response rates of less than 50% could lead to under- or overestimates of prevalence. Parts of the population, such as those in long-term care facilities or without a telephone, were not included in the analysis. Some demographic categories had small sample sizes; therefore, prevalence changes might not be detectable.
DISCLOSURES:
No specific funding was reported. The authors reported no potential conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
Hypertension prevalence remained stable in the United States at 30% after guidelines updated in 2017 lowered the threshold for the condition, while antihypertensive medication use rose about 3%, new research from the Centers for Disease Control and Prevention (CDC) shows.
METHODOLOGY:
- Researchers analyzed data from the Behavioral Risk Factor Surveillance System, a telephone survey of US adults aged 18 years and older.
- Self-reported diagnosed hypertension was defined as an affirmative response to the question, “Have you ever been told by a doctor, nurse, or other health professional that you have high blood pressure?”
- To determine treatment, respondents who answered the first question affirmatively were then asked, “Are you currently taking medicine for your high blood pressure?”
- Hypertension and treatment were assessed by age group (18-44, 45-64, and > 65 years), sex, race, ethnicity, level of education, and state of residence.
TAKEAWAY:
- The final analytic samples for 2017, 2019, and 2021 included 425,417, 392,100, and 410,318 participants, respectively.
- From 2017 to 2021, the overall age-standardized prevalence of hypertension did not change, remaining at almost exactly 30%.
- The age-standardized prevalence of antihypertensive medication use among individuals with hypertension increased by 3.1 percentage points, from 59.8% to 62.9%.
- Increases in medication use were seen in most sociodemographic groups; for example, in 2021, the prevalence was higher among women than among men (68.5% vs 59.4%), among adults aged ≥ 65 years than among those aged 18-44 years (92.5% vs 42.5%), and among Black patients than among White patients (71.3% vs 62%).
- Increases in medication use were also seen by state; use increased in 11 states, ranging from 52.2% in Utah to 72.8% in Mississippi in 2021, and did not decrease significantly in any state.
IN PRACTICE:
“These findings can be used to increase awareness of hypertension and promote lifestyle modifications and antihypertensive medication use to optimize blood pressure control and reduce disparities in prevalence and control,” the authors wrote.
SOURCE:
The study was led by Ahlia Sekkarie, PhD, of CDC’s Division for Heart Disease and Stroke Prevention, and published online in Morbidity and Mortality Weekly Report.
LIMITATIONS:
The study had several limitations. The findings were based on self-report. Median response rates of less than 50% could lead to under- or overestimates of prevalence. Parts of the population, such as those in long-term care facilities or without a telephone, were not included in the analysis. Some demographic categories had small sample sizes; therefore, prevalence changes might not be detectable.
DISCLOSURES:
No specific funding was reported. The authors reported no potential conflicts of interest.
A version of this article appeared on Medscape.com.
Healthy Lifestyle Linked to Lower Risk for IBS
TOPLINE:
Adherence to a higher number of the five key lifestyle behaviors — not smoking, vigorous physical activity, optimal sleep, high-quality diet, and moderate alcohol consumption — is associated with a lower risk for irritable bowel syndrome (IBS), new research suggested.
METHODOLOGY:
- Researchers assessed the association between healthy lifestyle behaviors and IBS incidence using UK Biobank data from 64,268 adults (mean age, 56 years; 55%, women) with no IBS diagnosis at baseline.
- Participants were enrolled during 2006-2010 and followed up to 2022.
- Self-reported healthy lifestyle behaviors were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality, and moderate alcohol intake.
TAKEAWAY:
- At baseline, 11.8% of participants reported none of the five healthy lifestyle behaviors, 32.1% reported one behavior, 34.1% reported two behaviors, and 21.9% reported three to five behaviors.
- During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases occurred.
- Adjusted hazard ratios associated with IBS incidence and having one, two, and three to five behaviors were 0.79, 0.64, and 0.58, respectively.
- Significant independent inverse associations with IBS incidence were seen for never smoking (0.86), high level of vigorous physical activity (0.83), and optimal sleep (0.73).
- After adjustment for age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, and family history of IBS, adherence to a higher number of healthy lifestyle behaviors remained significantly associated with a lower risk of incident IBS.
IN PRACTICE:
“This study provides evidence that adherence to a higher number of healthy lifestyle behaviors — never smoking, optimal sleep, high level of physical activity, high dietary quality and moderate alcohol intake — is significantly associated with a lower risk of subsequent IBS incidence. These findings suggest that lifestyle modifications should be considered as key primary prevention strategies for IBS,” the authors wrote.
SOURCE:
The study, led by Fai Fai Ho of The Chinese University of Hong Kong, was published online in Gut.
LIMITATIONS:
The study was observational, so it could not show cause and effect. It relied on self-report, which is not always accurate, and the findings may not be applicable to younger age groups. Lifestyle changes made during the follow-up period could not be considered.
DISCLOSURES:
The study was funded by the National Key R&D Program of China and the National Natural Science Foundation of China. The authors declared no competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
Adherence to a higher number of the five key lifestyle behaviors — not smoking, vigorous physical activity, optimal sleep, high-quality diet, and moderate alcohol consumption — is associated with a lower risk for irritable bowel syndrome (IBS), new research suggested.
METHODOLOGY:
- Researchers assessed the association between healthy lifestyle behaviors and IBS incidence using UK Biobank data from 64,268 adults (mean age, 56 years; 55%, women) with no IBS diagnosis at baseline.
- Participants were enrolled during 2006-2010 and followed up to 2022.
- Self-reported healthy lifestyle behaviors were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality, and moderate alcohol intake.
TAKEAWAY:
- At baseline, 11.8% of participants reported none of the five healthy lifestyle behaviors, 32.1% reported one behavior, 34.1% reported two behaviors, and 21.9% reported three to five behaviors.
- During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases occurred.
- Adjusted hazard ratios associated with IBS incidence and having one, two, and three to five behaviors were 0.79, 0.64, and 0.58, respectively.
- Significant independent inverse associations with IBS incidence were seen for never smoking (0.86), high level of vigorous physical activity (0.83), and optimal sleep (0.73).
- After adjustment for age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, and family history of IBS, adherence to a higher number of healthy lifestyle behaviors remained significantly associated with a lower risk of incident IBS.
IN PRACTICE:
“This study provides evidence that adherence to a higher number of healthy lifestyle behaviors — never smoking, optimal sleep, high level of physical activity, high dietary quality and moderate alcohol intake — is significantly associated with a lower risk of subsequent IBS incidence. These findings suggest that lifestyle modifications should be considered as key primary prevention strategies for IBS,” the authors wrote.
SOURCE:
The study, led by Fai Fai Ho of The Chinese University of Hong Kong, was published online in Gut.
LIMITATIONS:
The study was observational, so it could not show cause and effect. It relied on self-report, which is not always accurate, and the findings may not be applicable to younger age groups. Lifestyle changes made during the follow-up period could not be considered.
DISCLOSURES:
The study was funded by the National Key R&D Program of China and the National Natural Science Foundation of China. The authors declared no competing interests.
A version of this article appeared on Medscape.com.
TOPLINE:
Adherence to a higher number of the five key lifestyle behaviors — not smoking, vigorous physical activity, optimal sleep, high-quality diet, and moderate alcohol consumption — is associated with a lower risk for irritable bowel syndrome (IBS), new research suggested.
METHODOLOGY:
- Researchers assessed the association between healthy lifestyle behaviors and IBS incidence using UK Biobank data from 64,268 adults (mean age, 56 years; 55%, women) with no IBS diagnosis at baseline.
- Participants were enrolled during 2006-2010 and followed up to 2022.
- Self-reported healthy lifestyle behaviors were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality, and moderate alcohol intake.
TAKEAWAY:
- At baseline, 11.8% of participants reported none of the five healthy lifestyle behaviors, 32.1% reported one behavior, 34.1% reported two behaviors, and 21.9% reported three to five behaviors.
- During a mean follow-up of 12.6 years, 961 (1.5%) incident IBS cases occurred.
- Adjusted hazard ratios associated with IBS incidence and having one, two, and three to five behaviors were 0.79, 0.64, and 0.58, respectively.
- Significant independent inverse associations with IBS incidence were seen for never smoking (0.86), high level of vigorous physical activity (0.83), and optimal sleep (0.73).
- After adjustment for age, sex, employment status, geographic location, gastrointestinal infection, endometriosis, and family history of IBS, adherence to a higher number of healthy lifestyle behaviors remained significantly associated with a lower risk of incident IBS.
IN PRACTICE:
“This study provides evidence that adherence to a higher number of healthy lifestyle behaviors — never smoking, optimal sleep, high level of physical activity, high dietary quality and moderate alcohol intake — is significantly associated with a lower risk of subsequent IBS incidence. These findings suggest that lifestyle modifications should be considered as key primary prevention strategies for IBS,” the authors wrote.
SOURCE:
The study, led by Fai Fai Ho of The Chinese University of Hong Kong, was published online in Gut.
LIMITATIONS:
The study was observational, so it could not show cause and effect. It relied on self-report, which is not always accurate, and the findings may not be applicable to younger age groups. Lifestyle changes made during the follow-up period could not be considered.
DISCLOSURES:
The study was funded by the National Key R&D Program of China and the National Natural Science Foundation of China. The authors declared no competing interests.
A version of this article appeared on Medscape.com.
Dupilumab for Eosinophilic Esophagitis: How Is it Improving Treatment?
The US Food and Drug Administration approvals of dupilumab (Dupixent, Regeneron/Sanofi) for adults and children with eosinophilic esophagitis (EoE) affirmed the safety and efficacy of the drug, which is the first product indicated specifically for treatment of this disease.
The recent expanded approval for its use in kids aged 1 year and older imply that clinicians can prescribe it for just about any patient with the immune disorder.
But is dupilumab right for everyone?
What the Trials Said
Dupilumab, given by injection, is a recombinant human immunoglobulin-G4 monoclonal antibody that inhibits interleukin 4 (IL-4) and IL-13 signaling.
The first approval for EoE, on May 22, 2022, for adults and children aged 12 years and older weighing at least 40 kg, was based on data from 321 participants in the first two parts of a three-part phase 3 trial involving patients with EoE despite 8 weeks of high-dose proton pump inhibitor (PPI) therapy and with substantial symptom burden.
At 24 weeks, histologic remission occurred in 60% of patients in Part A of the trial and 59% in Part B who received a weekly 300-mg dose of dupilumab compared with 5% and 6% taking placebo. Additionally, Part A and B participants taking the drug weekly experienced a 69% and 64% reduction in disease symptoms, respectively, vs 32% and 41% for placebo. The drug also outperformed placebo in reducing patients’ esophageal eosinophilic counts and abnormal endoscopic findings.
The second approval, on January 25, 2024, for children aged 1 year and older weighing at least 15 kg, was based on data from a two-part, placebo-controlled trial involving 102 children, ages 1-11 years, with EoE. The study involved a 16-week treatment period and a 36-week extended period during which eligible children from the dupilumab group continued to receive their weight-based dose level and those who were on placebo switched to active treatment. The trial showed that a greater proportion of children taking the drug achieved histological remission.
A Major Advance but Temper Expectations
,” Philip Katz, MD, AGAF, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York City, said in an interview. “I’ve been using it since The New England Journal of Medicine paper was published about a year and a half ago , and as a slow adopter, I like it.”
Dr. Katz and his colleagues have been prescribing dupilumab mainly for patients who haven’t responded to other medications, mainly PPIs and steroids.
“We start people on it without stopping anything else,” Dr. Katz said. “Then, as symptoms evolve and people have a positive response, we stop the other medications. For example, in one patient who did very well on the drug, we stopped his steroids and now, we’re weaning him off his PPI. It’s a process. This is not a disease where you can rush people.”
The tempered approach is in part because of payer issues, he noted.
“It’s very difficult to get it reimbursed in the US if you haven’t tried something else first,” Dr. Katz said. “And because it’s still relatively new in this field, standard treatment is still used frequently.”
Although Dr. Katz has had “incredible success” with dupilumab so far, “nothing should be considered a miracle drug,” he said. “A couple of people have had injection reactions, and one person couldn’t tolerate the drug. So, while it seems to have an excellent response rate, it’s not 100%. Like any new drug, it will have to find its true success rate.”
Taking a Step-Up Approach
Like Dr. Katz, Evan Dellon, MD, MPH, AGAF, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina at Chapel Hill, North Carolina, is enthusiastic about dupilumab.
“It’s a boon to the field, and now, some real-world data are coming out and looking very much like the clinical trial data, which are reassuring,” said Dr. Dellon, a coauthor of The New England Journal of Medicine paper.
It’s been a “game changer,” particularly for people who weren’t doing well with their current treatments, he said. “In my practice, I’ve been seeing a lowish response rate for PPIs, and about 30%-40% not responding to topical steroids, since we don’t have a standard formulation for that. The diet elimination therapy is effective if people can do it well and adhere to it. But there’s a group of people who don’t respond, and probably, a larger group who can’t really do that treatment long term. So, the drug has been fantastic for those patients.”
Although the drug is approved for patients aged 1 year and older with no caveats, “it’s not the right medicine for every patient,” he said. “Patients in the clinical trials had EoE for 5 years, many of them were treatment refractory, and just under half had dilations and strictures,” he said. “They represent a certain group of patients.”
Dr. Dellon is taking a “step-up approach” to EoE treatment, first trying the standard interventions — PPIs, steroids, and an elimination diet — that many patients do respond to.
For new patients who choose medication therapy, he prescribes PPIs and then topical steroids and then steps up to dupilumab for patients who aren’t responding or who have a strong preference for starting the drug early.
In addition to EoE, the drug is approved for certain patients with atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. As such, Dr. Dellon said that he will try dupilumab early on in patients with multiple atopic conditions, such as asthma, eczema, or nasal disease.
“Even if their EoE is not that severe, those patients can still benefit from a more streamlined systemic therapy,” he said.
Challenges and Questions Still Remain
Not surprisingly, both Dr. Katz and Dr. Dellon pointed to dupilumab’s cost and the related challenge of convincing insurance companies to cover the drug as major challenges to more widespread use. The lack of long-term data also poses a challenge.
Side effects, which often stand in the way of the use of a new drug, are not an issue, for the most part, at least in the short term, according to Dr. Dellon. The most common side effects are discomfort, redness at the injection site, and pain related to the injection.
“Keeping the medication out of the refrigerator for a bit to bring it up to room temperature can help, as can doing the injection in the lower abdomen,” he said. “Otherwise, it’s well tolerated, with no side effects that are unique to EoE.”
Data from the third part of the clinical trial, which followed patients from weeks 24-52 of treatment, indicated that improvements in histological, symptomatic, endoscopic, and molecular features of EoE among patients taking weekly dupilumab continued or improved.
In my practice, “my observations have been that people are maintaining their responses,” said Dr. Dellon, a coauthor of the paper on the study’s third part.
However, one critical question is whether the dose intensity and/or frequency can be decreased over time without reducing the response rate.
“Hopefully, we’ll start getting data on that in the next year or two,” Dr. Dellon said. “It’s hard to do that yet because the drug has only been out for a year or year and a half, and people are just getting to that year of the initial dosing.”
Another question is how to use the drug in people who are different from the clinical trial population, such as those who have been responding to other therapies but want to switch, and people who are newly diagnosed but who have severe disease. Can the drug be used earlier in these populations?
Dr. Dellon would like to see a study that utilizes the new EoE index of severity metric to focus specifically on dupilumab use in patients with severe disease.
Early findings from his recent real-world study of 46 patients with severe disease who would not have qualified for the clinical trials found histologic, endoscopic, and symptom improvement in 91% of patients with refractory and fibrostenotic EoE after 6 months of dupilumab treatment.
While women tend to be well represented in the clinical trial, the drug needs to be tested in a more diverse population, Dr. Dellon noted. Research is underway looking at dupilumab effectiveness in people with different race/ethnicities.
EoE is more common among White people but that may be the result of a “detection issue,” he said. “When clinicians see a Black or Hispanic patient with dysphagia, for example, they may not be thinking of EoE. And there are also some data suggesting that EoE presents slightly differently in non-White populations, which again could decrease the suspicion for it. This is an area we need to learn more about.”
Don’t ‘Abandon’ Current Interventions
“We’ve got an exciting drug that is going to help a lot of people with a complex disease,” Dr. Katz said. “But we should not forget that there are other interventions that have been successful, and quite frankly, they don’t need to be abandoned.”
“Learn about the drug if you’ve never used it,” he advised. “Read the studies so you understand who the patients were as a baseline for where you’re going to use it. Be prepared to do the appropriate paperwork requirements to get approvals from insurers. And look for more literature because it’s coming.”
“Overall, dupilumab has really changed care in people with moderate to severe disease who are not responding or are intolerant to the other treatments,” Dr. Dellon said. “That’s the natural place for the medication to go at this point.”
Dr. Katz is a consultant to Phathom Pharma, Sebela Pharma, Medpace (not active), and Medtronic.
Dr. Dellon received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda. He served as a consultant to Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio. He also received educational grants from Allakos, Aqilion, Holoclara, and Invea.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration approvals of dupilumab (Dupixent, Regeneron/Sanofi) for adults and children with eosinophilic esophagitis (EoE) affirmed the safety and efficacy of the drug, which is the first product indicated specifically for treatment of this disease.
The recent expanded approval for its use in kids aged 1 year and older imply that clinicians can prescribe it for just about any patient with the immune disorder.
But is dupilumab right for everyone?
What the Trials Said
Dupilumab, given by injection, is a recombinant human immunoglobulin-G4 monoclonal antibody that inhibits interleukin 4 (IL-4) and IL-13 signaling.
The first approval for EoE, on May 22, 2022, for adults and children aged 12 years and older weighing at least 40 kg, was based on data from 321 participants in the first two parts of a three-part phase 3 trial involving patients with EoE despite 8 weeks of high-dose proton pump inhibitor (PPI) therapy and with substantial symptom burden.
At 24 weeks, histologic remission occurred in 60% of patients in Part A of the trial and 59% in Part B who received a weekly 300-mg dose of dupilumab compared with 5% and 6% taking placebo. Additionally, Part A and B participants taking the drug weekly experienced a 69% and 64% reduction in disease symptoms, respectively, vs 32% and 41% for placebo. The drug also outperformed placebo in reducing patients’ esophageal eosinophilic counts and abnormal endoscopic findings.
The second approval, on January 25, 2024, for children aged 1 year and older weighing at least 15 kg, was based on data from a two-part, placebo-controlled trial involving 102 children, ages 1-11 years, with EoE. The study involved a 16-week treatment period and a 36-week extended period during which eligible children from the dupilumab group continued to receive their weight-based dose level and those who were on placebo switched to active treatment. The trial showed that a greater proportion of children taking the drug achieved histological remission.
A Major Advance but Temper Expectations
,” Philip Katz, MD, AGAF, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York City, said in an interview. “I’ve been using it since The New England Journal of Medicine paper was published about a year and a half ago , and as a slow adopter, I like it.”
Dr. Katz and his colleagues have been prescribing dupilumab mainly for patients who haven’t responded to other medications, mainly PPIs and steroids.
“We start people on it without stopping anything else,” Dr. Katz said. “Then, as symptoms evolve and people have a positive response, we stop the other medications. For example, in one patient who did very well on the drug, we stopped his steroids and now, we’re weaning him off his PPI. It’s a process. This is not a disease where you can rush people.”
The tempered approach is in part because of payer issues, he noted.
“It’s very difficult to get it reimbursed in the US if you haven’t tried something else first,” Dr. Katz said. “And because it’s still relatively new in this field, standard treatment is still used frequently.”
Although Dr. Katz has had “incredible success” with dupilumab so far, “nothing should be considered a miracle drug,” he said. “A couple of people have had injection reactions, and one person couldn’t tolerate the drug. So, while it seems to have an excellent response rate, it’s not 100%. Like any new drug, it will have to find its true success rate.”
Taking a Step-Up Approach
Like Dr. Katz, Evan Dellon, MD, MPH, AGAF, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina at Chapel Hill, North Carolina, is enthusiastic about dupilumab.
“It’s a boon to the field, and now, some real-world data are coming out and looking very much like the clinical trial data, which are reassuring,” said Dr. Dellon, a coauthor of The New England Journal of Medicine paper.
It’s been a “game changer,” particularly for people who weren’t doing well with their current treatments, he said. “In my practice, I’ve been seeing a lowish response rate for PPIs, and about 30%-40% not responding to topical steroids, since we don’t have a standard formulation for that. The diet elimination therapy is effective if people can do it well and adhere to it. But there’s a group of people who don’t respond, and probably, a larger group who can’t really do that treatment long term. So, the drug has been fantastic for those patients.”
Although the drug is approved for patients aged 1 year and older with no caveats, “it’s not the right medicine for every patient,” he said. “Patients in the clinical trials had EoE for 5 years, many of them were treatment refractory, and just under half had dilations and strictures,” he said. “They represent a certain group of patients.”
Dr. Dellon is taking a “step-up approach” to EoE treatment, first trying the standard interventions — PPIs, steroids, and an elimination diet — that many patients do respond to.
For new patients who choose medication therapy, he prescribes PPIs and then topical steroids and then steps up to dupilumab for patients who aren’t responding or who have a strong preference for starting the drug early.
In addition to EoE, the drug is approved for certain patients with atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. As such, Dr. Dellon said that he will try dupilumab early on in patients with multiple atopic conditions, such as asthma, eczema, or nasal disease.
“Even if their EoE is not that severe, those patients can still benefit from a more streamlined systemic therapy,” he said.
Challenges and Questions Still Remain
Not surprisingly, both Dr. Katz and Dr. Dellon pointed to dupilumab’s cost and the related challenge of convincing insurance companies to cover the drug as major challenges to more widespread use. The lack of long-term data also poses a challenge.
Side effects, which often stand in the way of the use of a new drug, are not an issue, for the most part, at least in the short term, according to Dr. Dellon. The most common side effects are discomfort, redness at the injection site, and pain related to the injection.
“Keeping the medication out of the refrigerator for a bit to bring it up to room temperature can help, as can doing the injection in the lower abdomen,” he said. “Otherwise, it’s well tolerated, with no side effects that are unique to EoE.”
Data from the third part of the clinical trial, which followed patients from weeks 24-52 of treatment, indicated that improvements in histological, symptomatic, endoscopic, and molecular features of EoE among patients taking weekly dupilumab continued or improved.
In my practice, “my observations have been that people are maintaining their responses,” said Dr. Dellon, a coauthor of the paper on the study’s third part.
However, one critical question is whether the dose intensity and/or frequency can be decreased over time without reducing the response rate.
“Hopefully, we’ll start getting data on that in the next year or two,” Dr. Dellon said. “It’s hard to do that yet because the drug has only been out for a year or year and a half, and people are just getting to that year of the initial dosing.”
Another question is how to use the drug in people who are different from the clinical trial population, such as those who have been responding to other therapies but want to switch, and people who are newly diagnosed but who have severe disease. Can the drug be used earlier in these populations?
Dr. Dellon would like to see a study that utilizes the new EoE index of severity metric to focus specifically on dupilumab use in patients with severe disease.
Early findings from his recent real-world study of 46 patients with severe disease who would not have qualified for the clinical trials found histologic, endoscopic, and symptom improvement in 91% of patients with refractory and fibrostenotic EoE after 6 months of dupilumab treatment.
While women tend to be well represented in the clinical trial, the drug needs to be tested in a more diverse population, Dr. Dellon noted. Research is underway looking at dupilumab effectiveness in people with different race/ethnicities.
EoE is more common among White people but that may be the result of a “detection issue,” he said. “When clinicians see a Black or Hispanic patient with dysphagia, for example, they may not be thinking of EoE. And there are also some data suggesting that EoE presents slightly differently in non-White populations, which again could decrease the suspicion for it. This is an area we need to learn more about.”
Don’t ‘Abandon’ Current Interventions
“We’ve got an exciting drug that is going to help a lot of people with a complex disease,” Dr. Katz said. “But we should not forget that there are other interventions that have been successful, and quite frankly, they don’t need to be abandoned.”
“Learn about the drug if you’ve never used it,” he advised. “Read the studies so you understand who the patients were as a baseline for where you’re going to use it. Be prepared to do the appropriate paperwork requirements to get approvals from insurers. And look for more literature because it’s coming.”
“Overall, dupilumab has really changed care in people with moderate to severe disease who are not responding or are intolerant to the other treatments,” Dr. Dellon said. “That’s the natural place for the medication to go at this point.”
Dr. Katz is a consultant to Phathom Pharma, Sebela Pharma, Medpace (not active), and Medtronic.
Dr. Dellon received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda. He served as a consultant to Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio. He also received educational grants from Allakos, Aqilion, Holoclara, and Invea.
A version of this article appeared on Medscape.com.
The US Food and Drug Administration approvals of dupilumab (Dupixent, Regeneron/Sanofi) for adults and children with eosinophilic esophagitis (EoE) affirmed the safety and efficacy of the drug, which is the first product indicated specifically for treatment of this disease.
The recent expanded approval for its use in kids aged 1 year and older imply that clinicians can prescribe it for just about any patient with the immune disorder.
But is dupilumab right for everyone?
What the Trials Said
Dupilumab, given by injection, is a recombinant human immunoglobulin-G4 monoclonal antibody that inhibits interleukin 4 (IL-4) and IL-13 signaling.
The first approval for EoE, on May 22, 2022, for adults and children aged 12 years and older weighing at least 40 kg, was based on data from 321 participants in the first two parts of a three-part phase 3 trial involving patients with EoE despite 8 weeks of high-dose proton pump inhibitor (PPI) therapy and with substantial symptom burden.
At 24 weeks, histologic remission occurred in 60% of patients in Part A of the trial and 59% in Part B who received a weekly 300-mg dose of dupilumab compared with 5% and 6% taking placebo. Additionally, Part A and B participants taking the drug weekly experienced a 69% and 64% reduction in disease symptoms, respectively, vs 32% and 41% for placebo. The drug also outperformed placebo in reducing patients’ esophageal eosinophilic counts and abnormal endoscopic findings.
The second approval, on January 25, 2024, for children aged 1 year and older weighing at least 15 kg, was based on data from a two-part, placebo-controlled trial involving 102 children, ages 1-11 years, with EoE. The study involved a 16-week treatment period and a 36-week extended period during which eligible children from the dupilumab group continued to receive their weight-based dose level and those who were on placebo switched to active treatment. The trial showed that a greater proportion of children taking the drug achieved histological remission.
A Major Advance but Temper Expectations
,” Philip Katz, MD, AGAF, professor of medicine in the gastroenterology division at Weill Cornell Medicine, New York City, said in an interview. “I’ve been using it since The New England Journal of Medicine paper was published about a year and a half ago , and as a slow adopter, I like it.”
Dr. Katz and his colleagues have been prescribing dupilumab mainly for patients who haven’t responded to other medications, mainly PPIs and steroids.
“We start people on it without stopping anything else,” Dr. Katz said. “Then, as symptoms evolve and people have a positive response, we stop the other medications. For example, in one patient who did very well on the drug, we stopped his steroids and now, we’re weaning him off his PPI. It’s a process. This is not a disease where you can rush people.”
The tempered approach is in part because of payer issues, he noted.
“It’s very difficult to get it reimbursed in the US if you haven’t tried something else first,” Dr. Katz said. “And because it’s still relatively new in this field, standard treatment is still used frequently.”
Although Dr. Katz has had “incredible success” with dupilumab so far, “nothing should be considered a miracle drug,” he said. “A couple of people have had injection reactions, and one person couldn’t tolerate the drug. So, while it seems to have an excellent response rate, it’s not 100%. Like any new drug, it will have to find its true success rate.”
Taking a Step-Up Approach
Like Dr. Katz, Evan Dellon, MD, MPH, AGAF, director of the Center for Esophageal Diseases and Swallowing at the University of North Carolina at Chapel Hill, North Carolina, is enthusiastic about dupilumab.
“It’s a boon to the field, and now, some real-world data are coming out and looking very much like the clinical trial data, which are reassuring,” said Dr. Dellon, a coauthor of The New England Journal of Medicine paper.
It’s been a “game changer,” particularly for people who weren’t doing well with their current treatments, he said. “In my practice, I’ve been seeing a lowish response rate for PPIs, and about 30%-40% not responding to topical steroids, since we don’t have a standard formulation for that. The diet elimination therapy is effective if people can do it well and adhere to it. But there’s a group of people who don’t respond, and probably, a larger group who can’t really do that treatment long term. So, the drug has been fantastic for those patients.”
Although the drug is approved for patients aged 1 year and older with no caveats, “it’s not the right medicine for every patient,” he said. “Patients in the clinical trials had EoE for 5 years, many of them were treatment refractory, and just under half had dilations and strictures,” he said. “They represent a certain group of patients.”
Dr. Dellon is taking a “step-up approach” to EoE treatment, first trying the standard interventions — PPIs, steroids, and an elimination diet — that many patients do respond to.
For new patients who choose medication therapy, he prescribes PPIs and then topical steroids and then steps up to dupilumab for patients who aren’t responding or who have a strong preference for starting the drug early.
In addition to EoE, the drug is approved for certain patients with atopic dermatitis, asthma, and chronic rhinosinusitis with nasal polyposis. As such, Dr. Dellon said that he will try dupilumab early on in patients with multiple atopic conditions, such as asthma, eczema, or nasal disease.
“Even if their EoE is not that severe, those patients can still benefit from a more streamlined systemic therapy,” he said.
Challenges and Questions Still Remain
Not surprisingly, both Dr. Katz and Dr. Dellon pointed to dupilumab’s cost and the related challenge of convincing insurance companies to cover the drug as major challenges to more widespread use. The lack of long-term data also poses a challenge.
Side effects, which often stand in the way of the use of a new drug, are not an issue, for the most part, at least in the short term, according to Dr. Dellon. The most common side effects are discomfort, redness at the injection site, and pain related to the injection.
“Keeping the medication out of the refrigerator for a bit to bring it up to room temperature can help, as can doing the injection in the lower abdomen,” he said. “Otherwise, it’s well tolerated, with no side effects that are unique to EoE.”
Data from the third part of the clinical trial, which followed patients from weeks 24-52 of treatment, indicated that improvements in histological, symptomatic, endoscopic, and molecular features of EoE among patients taking weekly dupilumab continued or improved.
In my practice, “my observations have been that people are maintaining their responses,” said Dr. Dellon, a coauthor of the paper on the study’s third part.
However, one critical question is whether the dose intensity and/or frequency can be decreased over time without reducing the response rate.
“Hopefully, we’ll start getting data on that in the next year or two,” Dr. Dellon said. “It’s hard to do that yet because the drug has only been out for a year or year and a half, and people are just getting to that year of the initial dosing.”
Another question is how to use the drug in people who are different from the clinical trial population, such as those who have been responding to other therapies but want to switch, and people who are newly diagnosed but who have severe disease. Can the drug be used earlier in these populations?
Dr. Dellon would like to see a study that utilizes the new EoE index of severity metric to focus specifically on dupilumab use in patients with severe disease.
Early findings from his recent real-world study of 46 patients with severe disease who would not have qualified for the clinical trials found histologic, endoscopic, and symptom improvement in 91% of patients with refractory and fibrostenotic EoE after 6 months of dupilumab treatment.
While women tend to be well represented in the clinical trial, the drug needs to be tested in a more diverse population, Dr. Dellon noted. Research is underway looking at dupilumab effectiveness in people with different race/ethnicities.
EoE is more common among White people but that may be the result of a “detection issue,” he said. “When clinicians see a Black or Hispanic patient with dysphagia, for example, they may not be thinking of EoE. And there are also some data suggesting that EoE presents slightly differently in non-White populations, which again could decrease the suspicion for it. This is an area we need to learn more about.”
Don’t ‘Abandon’ Current Interventions
“We’ve got an exciting drug that is going to help a lot of people with a complex disease,” Dr. Katz said. “But we should not forget that there are other interventions that have been successful, and quite frankly, they don’t need to be abandoned.”
“Learn about the drug if you’ve never used it,” he advised. “Read the studies so you understand who the patients were as a baseline for where you’re going to use it. Be prepared to do the appropriate paperwork requirements to get approvals from insurers. And look for more literature because it’s coming.”
“Overall, dupilumab has really changed care in people with moderate to severe disease who are not responding or are intolerant to the other treatments,” Dr. Dellon said. “That’s the natural place for the medication to go at this point.”
Dr. Katz is a consultant to Phathom Pharma, Sebela Pharma, Medpace (not active), and Medtronic.
Dr. Dellon received research funding from Adare/Ellodi, Allakos, Arena/Pfizer, AstraZeneca, Eupraxia, Ferring, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos/BMS, Regeneron, Revolo, and Shire/Takeda. He served as a consultant to Abbott, AbbVie, Adare/Ellodi, Aimmune, Akesobio, Alfasigma, ALK, Allakos, Amgen, Aqilion, Arena/Pfizer, Aslan, AstraZeneca, Avir, Biorasi, Calypso, Celgene/Receptos/BMS, Celldex, Eli Lilly, EsoCap, Eupraxia, Dr. Falk Pharma, Ferring, GSK, Gossamer Bio, Holoclara, Invea, Knightpoint, Landos, LucidDx, Morphic, Nexstone Immunology/Uniquity, Nutricia, Parexel/Calyx, Phathom, Regeneron, Revolo, Robarts/Alimentiv, Salix, Sanofi, Shire/Takeda, Target RWE, and Upstream Bio. He also received educational grants from Allakos, Aqilion, Holoclara, and Invea.
A version of this article appeared on Medscape.com.
Many Older Adults Don’t Receive Palliative Care Before Death
A prognostic tool may facilitate the early identification of older adults in the community who would benefit from palliative care in their final years, new research from Canada suggested.
The analysis of data from close to a quarter million community-dwelling older adults in Ontario with at least one interRAI (Resident Assessment Instrument) home care assessment showed that only half of those with an estimated survival of fewer than 3 months received at least one palliative home care visit before death.
“One of the challenges and a barrier to accessing palliative home care is the difficulty of predicting survival,” Amy Hsu, PhD, an investigator at the Bruyère Research Institute in Ottawa, Ontario, Canada, told this news organization. “Clinicians are good at prognosticating when a patient might be entering their last 3-6 weeks of life, but they have a harder time predicting if someone will survive 6 months or longer.”
The team developed the Risk Evaluation for Support: Predictions for Elder-life in their Communities Tool (RESPECT) to see whether access to predicted survival data could inform conversations about a patient’s status and palliative care needs.
The study was published online in the Canadian Medical Association Journal.
Setting Care Goals
Researchers analyzed population health administrative data from Ontario involving home care clients who received at least one interRAI Home Care assessment between April 2018 and September 2019. The cohort included 247,377 adults (62% women) with a mean age of 80.1 years at the time of assessment. Comorbidities, including congestive heart failure, coronary artery disease, cancer, and chronic obstructive pulmonary disease, as well as symptoms of health instability, were more prevalent among those at higher risk of dying.
The team used an updated, validated version of RESPECT to predict survival.
Only 2.6% of home care clients had received a clinician diagnosis of an end-stage disease, which was more prevalent among those at highest mortality risk (77.9%). Most clients (74.5%) required extensive assistance in performing instrumental activities of daily living (ADLs, score ≤ 4), and half (50.3%) were less able to perform ADLs in the last 3 months of life.
Within the cohort, 75% of patients with a predicted median survival of fewer than 3 months, 55.4% of those with a predicted median survival between 3 and 6 months, and 40.7% of those with a predicted median survival between 6 and 12 months died within 6 months of the home care assessment.
Among decedents, 50.6% of those with a RESPECT-estimated median survival of fewer than 3 months received at least one nonphysician palliative home care visit before death. Less than a third (27.8%) received at least one palliative home care visit from a physician.
The proportion of those who received at least one nonphysician visit fell to 38.7% among those with a median survival of between 3 and 6 months and to 29.5% among those with a median survival of between 6 and 12 months.
Patients who received at least one palliative home care visit (from either physicians or nonphysician home care providers) within 6 months of an assessment had clinical characteristics similar to those who did not receive a visit. However, those who did not receive palliative home care were more likely to not have been identified by a clinician as being in their past 6 months of life.
“These results reinforce the role of clinicians in identifying older adults who may be in their last 6 months of life as an important component for the receipt of palliative home care and highlight the value of RESPECT in supplementing clinicians’ assessments of prognosis,” the authors wrote.
“Our goal is to use data and tools like RESPECT to help individuals living with a life-limiting illness have conversations about what their end-of-life care goals and wishes may be and discuss whether a referral to palliative care is appropriate or needed,” Dr. Hsu added. “Data about life expectancy could be helpful for framing these conversations.”
The researchers are working with partners in home, community care, and long-term care to implement RESPECT in their settings.
‘Valuable Tool’
Guohua Li, MD, DrPH, professor of epidemiology and anesthesiology at Columbia University Mailman School of Public Health and Vagelos College of Physicians and Surgeons in New York City, commented on the findings for this news organization. He noted that the study is “rigorously designed and meticulously analyzed. The findings are of high validity and population health significance.”
The findings are comparable with what is seen in the United States and Canada, he said, where about 50% of terminally ill patients die at home or in hospice. However, palliative care outside of North America “varies greatly, and in many developing countries, [it] is still in its infancy.”
As a mortality risk prediction algorithm, “RESPECT seems to perform reasonably well,” he said. “If incorporated into the electronic health record, it could be a valuable tool for clinicians to identify patients with less than 6 months of life expectancy and deliver palliative care to these patients. RESPECT appears to be particularly beneficial for home care patients without a clinically diagnosed terminal disease.”
That said, he added, “RESPECT should be viewed as a clinical decision support tool. It is no substitute for clinicians or clinical judgment. Based on the data presented in the paper, the algorithm tends to overestimate the short-term mortality risk for home care patients, therefore resulting in many false alarms.”
The study was supported by the Canadian Institutes of Health Research and the Associated Medical Services. Dr. Hsu is an executive lead on the steering committee of the Ontario Centres for Learning, Research, and Innovation in Long-Term Care. Funding for the centers comes from the Ontario Ministry of Health and Ministry of Long-Term Care and is partially administered by the Bruyère Research Institute. Dr. Li reported no relevant financial interests.
A version of this article appeared on Medscape.com.
A prognostic tool may facilitate the early identification of older adults in the community who would benefit from palliative care in their final years, new research from Canada suggested.
The analysis of data from close to a quarter million community-dwelling older adults in Ontario with at least one interRAI (Resident Assessment Instrument) home care assessment showed that only half of those with an estimated survival of fewer than 3 months received at least one palliative home care visit before death.
“One of the challenges and a barrier to accessing palliative home care is the difficulty of predicting survival,” Amy Hsu, PhD, an investigator at the Bruyère Research Institute in Ottawa, Ontario, Canada, told this news organization. “Clinicians are good at prognosticating when a patient might be entering their last 3-6 weeks of life, but they have a harder time predicting if someone will survive 6 months or longer.”
The team developed the Risk Evaluation for Support: Predictions for Elder-life in their Communities Tool (RESPECT) to see whether access to predicted survival data could inform conversations about a patient’s status and palliative care needs.
The study was published online in the Canadian Medical Association Journal.
Setting Care Goals
Researchers analyzed population health administrative data from Ontario involving home care clients who received at least one interRAI Home Care assessment between April 2018 and September 2019. The cohort included 247,377 adults (62% women) with a mean age of 80.1 years at the time of assessment. Comorbidities, including congestive heart failure, coronary artery disease, cancer, and chronic obstructive pulmonary disease, as well as symptoms of health instability, were more prevalent among those at higher risk of dying.
The team used an updated, validated version of RESPECT to predict survival.
Only 2.6% of home care clients had received a clinician diagnosis of an end-stage disease, which was more prevalent among those at highest mortality risk (77.9%). Most clients (74.5%) required extensive assistance in performing instrumental activities of daily living (ADLs, score ≤ 4), and half (50.3%) were less able to perform ADLs in the last 3 months of life.
Within the cohort, 75% of patients with a predicted median survival of fewer than 3 months, 55.4% of those with a predicted median survival between 3 and 6 months, and 40.7% of those with a predicted median survival between 6 and 12 months died within 6 months of the home care assessment.
Among decedents, 50.6% of those with a RESPECT-estimated median survival of fewer than 3 months received at least one nonphysician palliative home care visit before death. Less than a third (27.8%) received at least one palliative home care visit from a physician.
The proportion of those who received at least one nonphysician visit fell to 38.7% among those with a median survival of between 3 and 6 months and to 29.5% among those with a median survival of between 6 and 12 months.
Patients who received at least one palliative home care visit (from either physicians or nonphysician home care providers) within 6 months of an assessment had clinical characteristics similar to those who did not receive a visit. However, those who did not receive palliative home care were more likely to not have been identified by a clinician as being in their past 6 months of life.
“These results reinforce the role of clinicians in identifying older adults who may be in their last 6 months of life as an important component for the receipt of palliative home care and highlight the value of RESPECT in supplementing clinicians’ assessments of prognosis,” the authors wrote.
“Our goal is to use data and tools like RESPECT to help individuals living with a life-limiting illness have conversations about what their end-of-life care goals and wishes may be and discuss whether a referral to palliative care is appropriate or needed,” Dr. Hsu added. “Data about life expectancy could be helpful for framing these conversations.”
The researchers are working with partners in home, community care, and long-term care to implement RESPECT in their settings.
‘Valuable Tool’
Guohua Li, MD, DrPH, professor of epidemiology and anesthesiology at Columbia University Mailman School of Public Health and Vagelos College of Physicians and Surgeons in New York City, commented on the findings for this news organization. He noted that the study is “rigorously designed and meticulously analyzed. The findings are of high validity and population health significance.”
The findings are comparable with what is seen in the United States and Canada, he said, where about 50% of terminally ill patients die at home or in hospice. However, palliative care outside of North America “varies greatly, and in many developing countries, [it] is still in its infancy.”
As a mortality risk prediction algorithm, “RESPECT seems to perform reasonably well,” he said. “If incorporated into the electronic health record, it could be a valuable tool for clinicians to identify patients with less than 6 months of life expectancy and deliver palliative care to these patients. RESPECT appears to be particularly beneficial for home care patients without a clinically diagnosed terminal disease.”
That said, he added, “RESPECT should be viewed as a clinical decision support tool. It is no substitute for clinicians or clinical judgment. Based on the data presented in the paper, the algorithm tends to overestimate the short-term mortality risk for home care patients, therefore resulting in many false alarms.”
The study was supported by the Canadian Institutes of Health Research and the Associated Medical Services. Dr. Hsu is an executive lead on the steering committee of the Ontario Centres for Learning, Research, and Innovation in Long-Term Care. Funding for the centers comes from the Ontario Ministry of Health and Ministry of Long-Term Care and is partially administered by the Bruyère Research Institute. Dr. Li reported no relevant financial interests.
A version of this article appeared on Medscape.com.
A prognostic tool may facilitate the early identification of older adults in the community who would benefit from palliative care in their final years, new research from Canada suggested.
The analysis of data from close to a quarter million community-dwelling older adults in Ontario with at least one interRAI (Resident Assessment Instrument) home care assessment showed that only half of those with an estimated survival of fewer than 3 months received at least one palliative home care visit before death.
“One of the challenges and a barrier to accessing palliative home care is the difficulty of predicting survival,” Amy Hsu, PhD, an investigator at the Bruyère Research Institute in Ottawa, Ontario, Canada, told this news organization. “Clinicians are good at prognosticating when a patient might be entering their last 3-6 weeks of life, but they have a harder time predicting if someone will survive 6 months or longer.”
The team developed the Risk Evaluation for Support: Predictions for Elder-life in their Communities Tool (RESPECT) to see whether access to predicted survival data could inform conversations about a patient’s status and palliative care needs.
The study was published online in the Canadian Medical Association Journal.
Setting Care Goals
Researchers analyzed population health administrative data from Ontario involving home care clients who received at least one interRAI Home Care assessment between April 2018 and September 2019. The cohort included 247,377 adults (62% women) with a mean age of 80.1 years at the time of assessment. Comorbidities, including congestive heart failure, coronary artery disease, cancer, and chronic obstructive pulmonary disease, as well as symptoms of health instability, were more prevalent among those at higher risk of dying.
The team used an updated, validated version of RESPECT to predict survival.
Only 2.6% of home care clients had received a clinician diagnosis of an end-stage disease, which was more prevalent among those at highest mortality risk (77.9%). Most clients (74.5%) required extensive assistance in performing instrumental activities of daily living (ADLs, score ≤ 4), and half (50.3%) were less able to perform ADLs in the last 3 months of life.
Within the cohort, 75% of patients with a predicted median survival of fewer than 3 months, 55.4% of those with a predicted median survival between 3 and 6 months, and 40.7% of those with a predicted median survival between 6 and 12 months died within 6 months of the home care assessment.
Among decedents, 50.6% of those with a RESPECT-estimated median survival of fewer than 3 months received at least one nonphysician palliative home care visit before death. Less than a third (27.8%) received at least one palliative home care visit from a physician.
The proportion of those who received at least one nonphysician visit fell to 38.7% among those with a median survival of between 3 and 6 months and to 29.5% among those with a median survival of between 6 and 12 months.
Patients who received at least one palliative home care visit (from either physicians or nonphysician home care providers) within 6 months of an assessment had clinical characteristics similar to those who did not receive a visit. However, those who did not receive palliative home care were more likely to not have been identified by a clinician as being in their past 6 months of life.
“These results reinforce the role of clinicians in identifying older adults who may be in their last 6 months of life as an important component for the receipt of palliative home care and highlight the value of RESPECT in supplementing clinicians’ assessments of prognosis,” the authors wrote.
“Our goal is to use data and tools like RESPECT to help individuals living with a life-limiting illness have conversations about what their end-of-life care goals and wishes may be and discuss whether a referral to palliative care is appropriate or needed,” Dr. Hsu added. “Data about life expectancy could be helpful for framing these conversations.”
The researchers are working with partners in home, community care, and long-term care to implement RESPECT in their settings.
‘Valuable Tool’
Guohua Li, MD, DrPH, professor of epidemiology and anesthesiology at Columbia University Mailman School of Public Health and Vagelos College of Physicians and Surgeons in New York City, commented on the findings for this news organization. He noted that the study is “rigorously designed and meticulously analyzed. The findings are of high validity and population health significance.”
The findings are comparable with what is seen in the United States and Canada, he said, where about 50% of terminally ill patients die at home or in hospice. However, palliative care outside of North America “varies greatly, and in many developing countries, [it] is still in its infancy.”
As a mortality risk prediction algorithm, “RESPECT seems to perform reasonably well,” he said. “If incorporated into the electronic health record, it could be a valuable tool for clinicians to identify patients with less than 6 months of life expectancy and deliver palliative care to these patients. RESPECT appears to be particularly beneficial for home care patients without a clinically diagnosed terminal disease.”
That said, he added, “RESPECT should be viewed as a clinical decision support tool. It is no substitute for clinicians or clinical judgment. Based on the data presented in the paper, the algorithm tends to overestimate the short-term mortality risk for home care patients, therefore resulting in many false alarms.”
The study was supported by the Canadian Institutes of Health Research and the Associated Medical Services. Dr. Hsu is an executive lead on the steering committee of the Ontario Centres for Learning, Research, and Innovation in Long-Term Care. Funding for the centers comes from the Ontario Ministry of Health and Ministry of Long-Term Care and is partially administered by the Bruyère Research Institute. Dr. Li reported no relevant financial interests.
A version of this article appeared on Medscape.com.
FROM THE CANADIAN MEDICAL ASSOCIATION JOURNAL