Clinician Reviews

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

BERLIN – Tapinarof cream is highly effective, safe, and well tolerated for the treatment of atopic dermatitis (AD) in adults as well as children as young as 2 years of age, according to results of two pivotal trials presented at the at the annual congress of the European Academy of Dermatology and Venereology.

If approved for AD, one advantage of tapinarof cream relative to topical corticosteroids is potential use “without restrictions on duration, extent, or site of application,” reported Jonathan I. Silverberg, MD, PhD, MPH, director of clinical research, George Washington University, Washington.

Tapinarof cream, 1%, an aryl hydrocarbon receptor agonist, was approved in 2022 for treating plaque psoriasis in adults.

In the two phase 3 trials, ADORING 1 and ADORING 2, which were presented together at the meeting, the primary endpoint was Validated Investigator Global Assessment (vIGA) for AD of 0 (clear) or 1 (almost clear) at 8 weeks. For this endpoint and all secondary endpoints, the relative advantage of the active cream over the vehicle alone was about the same in both studies.

For example, the vIGA clear or almost clear response was met by 45.4% and 46.4% of those in the experimental arm of ADORING 1 and 2, respectively, but only 13.9% and 18.0% in the control arms (P < .0001 for both).

For the secondary endpoint of Eczema Area and Severity Index (EASI75), signifying 75% clearance of skin lesions, the response rates were 55.8% and 59.1% in the two trials, but only 22.9% and 24.1% in the respective control arms (P < .0001 for both).

The two identically designed trials randomized patients with moderate to severe AD in a 2:1 ratio to tapinarof cream or vehicle alone. There were 407 patients ages 2-81 years in ADORING I and 406 in ADORING 2. Patients were instructed to apply the active cream or vehicle once per day.

The safety data for tapinarof in these studies was generally consistent with the experience with this agent in plaque psoriasis. According to Dr. Silverberg, there was a modest increase in reports of headache early in this study, but these were transient. Follicular events were also more common on tapinarof than on its vehicle, but Dr. Silverberg said that the rate of discontinuations for adverse events, although low in both arms, was numerically lower in the active treatment arm in both trials.

“There were reports of contact dermatitis in the psoriasis studies, but we have not seen this in the AD trials,” Dr. Silverberg said.
 

Itch control evaluated

In a separate presentation of ADORING 1 and 2 results, Eric Simpson, MD, professor of dermatology, Oregon Health & Science University, Portland, provided detailed information about itch control, which was evaluated with the Peak Pruritus–Numerical Rating Scale (PP-NRS).

Ted Bosworth/MDedge News

“The PP-NRS considers a person’s worst itch over the past 24 hours based on an 11-point scale,” explained Dr. Simpson, who said that patients scored itch daily with comparisons made at weeks 1, 2, 4, and 8.

Over time, pruritus scores fell in both groups, but reductions were far steeper among those in the active treatment arms.

“In ADORING 1, there were greater reductions in itch as early as day 1,” Dr. Simpson reported. Although the differences in itch were not detected until day 2 in ADORING 2, the differences were already significant and clinically meaningful in both studies by the end of the first week.

By week 8, the mean reductions in PP-NRS scores were 2.6 and 2.4 in the vehicle arms of ADORING 1 and 2, respectively. In the treatment arm, the reduction was 4.1 points in both arms (P < .0001 for both studies).
 

Forty-eight–week follow-up planned

More than 90% of patients in both studies have rolled over into the open-label extension ADORING 3 trial, with a planned follow-up of 48 weeks, according to Dr. Silverberg, who said that those in the placebo arm have been crossed over to tapinarof.

The response and the safety appear to be similar in adults and children, although Dr. Silverberg said that further analyses of outcomes by age are planned. He noted that there is also an ongoing study of tapinarof in children with plaque psoriasis.

In AD in particular, Dr. Silverberg said there is “an unmet need” for a topical nonsteroidal anti-inflammatory. While topical corticosteroids are a mainstay of AD therapy in children as well as adults, he noted the limitations of these drugs, including that they can only be applied for limited periods.

Tapinarof binds to the aryl hydrocarbon receptor (AhR), which regulates immune function in the skin and is expressed in many skin cell types. By inhibiting AhR, tapinarof blocks cytokine activation and has an antioxidant effect.

Adelaide A. Hebert, MD, professor and director of pediatric dermatology, McGovern Medical School at UTHealth, Houston, has participated in clinical studies of tapinarof for AD, and said she has been impressed with its efficacy and tolerability in children as well as adults. In the case of children, parents, as well as patients, “valued the rapid onset of disease control, the once-daily application regimen, and the itch control,” she said in an interview after the meeting.

If approved, Dr. Hebert said, “this novel steroid-free medication has the potential to change the management arena for pediatric and adult patients with moderate to severe atopic dermatitis.”

The recent introduction of new systemic therapies for AD, such as JAK inhibitors, has increased options for AD control, but “we still need effective and safe topical therapies, especially in children and young adults,” said Sonja Ständer, MD, head of the Interdisciplinary Center for Chronic Pruritus, University of Münster (Germany). Author of a comprehensive review article on AD in the New England Journal of Medicine 2 years ago, Dr. Ständer said results from the phase 3 topical tapinarof trials, as well as the phase 3 topical ruxolitinib trials, which were also presented as late breakers at the 2023 EADV meeting, provide “hope that an alternative to topical steroids will soon be available.”

Based on their safety and rapid control of itch in children with AD, “these will complement our current portfolio of topical therapies very well and have the potential to replace topical steroids early in therapy or to replace them altogether,” she told this news organization.

Dermavant Sciences, manufacturer of tapinarof, anticipates filing for Food and Drug Administration approval for AD in the first quarter of 2024, according to a company statement.

Dr. Silverberg and Dr. Simpson reported financial relationships with multiple pharmaceutical companies, including Dermavant, which provided funding for the ADORING trials. Dr. Hebert has financial relationship with more than 15 pharmaceutical companies, including Dermavent and other companies that have or are developing therapies for AD. Dr. Ständer reported financial relationships with Beiersdorf, Eli Lilly, Galderma, Kiniksa, Pfizer, and Sanofi.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Excess consumption of red meat, whether processed or not, is linked to a greater risk for developing type 2 diabetes. This association was confirmed by a new study published in the American Journal of Clinical Nutrition, a data analysis of nearly 217,000 people who were monitored for three decades as part of several cohort studies. “Our study supports the current dietary recommendations of limiting consumption of red meat and highlights the importance of different alternative sources of protein in preventing type 2 diabetes,” the researchers wrote.

Consumption and risk

The study included men and women who took part in the Nurses’ Health Study, the Nurses’ Health Study II, or the Health Professionals Follow-up Study. Questionnaires were used to collect data every 2-4 years on the frequency of specific food consumption. Information on the onset of diseases and on different health-related aspects was collected every 2 years.

Those who consumed more red meat had a higher body mass index, higher total energy intake, and greater likelihood of being a smoker. They were physically less active and less likely to take multivitamins. In a follow-up of 5.48 million person-years, 22,761 cases of type 2 diabetes were recorded.

The link between consumption of processed and unprocessed red meat (and both combined) and a higher risk of diabetes was observed in all cohorts when analyzed separately and jointly. The people in the highest quintile for combined red meat consumption had a 2% greater risk of developing the disease, compared with those in the lowest quintile. The risk increases associated with processed and unprocessed meat were 51% and 40%, respectively. One additional serving per day of processed red meat was associated with a 1.46-fold greater risk of diabetes. This risk was 1.24 times greater for unprocessed meat and 1.28 times greater for both types combined.

The associations had a linear dose-response relationship and remained firm even after accounting for BMI, which the researchers stressed could be a mediating factor. Finally, the associations were stronger when considering the average cumulative consumption over the 30-year follow-up period and still stronger following the calibration of meat consumption with data extrapolated from food registers. The latter step was taken to account for measurement errors.
 

Alternatives are better

By analyzing alternative protein sources, the researchers discovered that nuts and legumes are associated with the most substantial reductions in diabetes risk. “This discovery is consistent with the evidence that shows that sources of unsaturated fatty acids and antioxidants have beneficial effects on glycemic control, insulin response, and inflammation,” they wrote. By replacing a serving of processed red meat, unprocessed red meat, or a combination of the two with a serving of dry fruit or legumes, the risk of developing diabetes is lowered by 30%, 41%, and 29%, respectively. Replacing red meat with a serving of dairy products is also associated with a reduced risk.

Confirmation

Several biological mechanisms could contribute to the increased risk for type 2 diabetes in people who consume red meat. The high level of saturated fats or the relatively low level of polyunsaturated fats, heme iron, or the high nitrate content in processed red meats could play a role. A strong positive association between consumption of this meat, particularly when processed, and the onset of diabetes has already emerged from other studies, including a trial carried out several years ago in the same cohorts. “In the current study, we wanted to look at this association in the same three cohorts in more detail, with over 9,000 additional cases of type 2 diabetes documented with extensive follow-up,” the researchers explained.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Excess consumption of red meat, whether processed or not, is linked to a greater risk for developing type 2 diabetes. This association was confirmed by a new study published in the American Journal of Clinical Nutrition, a data analysis of nearly 217,000 people who were monitored for three decades as part of several cohort studies. “Our study supports the current dietary recommendations of limiting consumption of red meat and highlights the importance of different alternative sources of protein in preventing type 2 diabetes,” the researchers wrote.

Consumption and risk

The study included men and women who took part in the Nurses’ Health Study, the Nurses’ Health Study II, or the Health Professionals Follow-up Study. Questionnaires were used to collect data every 2-4 years on the frequency of specific food consumption. Information on the onset of diseases and on different health-related aspects was collected every 2 years.

Those who consumed more red meat had a higher body mass index, higher total energy intake, and greater likelihood of being a smoker. They were physically less active and less likely to take multivitamins. In a follow-up of 5.48 million person-years, 22,761 cases of type 2 diabetes were recorded.

The link between consumption of processed and unprocessed red meat (and both combined) and a higher risk of diabetes was observed in all cohorts when analyzed separately and jointly. The people in the highest quintile for combined red meat consumption had a 2% greater risk of developing the disease, compared with those in the lowest quintile. The risk increases associated with processed and unprocessed meat were 51% and 40%, respectively. One additional serving per day of processed red meat was associated with a 1.46-fold greater risk of diabetes. This risk was 1.24 times greater for unprocessed meat and 1.28 times greater for both types combined.

The associations had a linear dose-response relationship and remained firm even after accounting for BMI, which the researchers stressed could be a mediating factor. Finally, the associations were stronger when considering the average cumulative consumption over the 30-year follow-up period and still stronger following the calibration of meat consumption with data extrapolated from food registers. The latter step was taken to account for measurement errors.
 

Alternatives are better

By analyzing alternative protein sources, the researchers discovered that nuts and legumes are associated with the most substantial reductions in diabetes risk. “This discovery is consistent with the evidence that shows that sources of unsaturated fatty acids and antioxidants have beneficial effects on glycemic control, insulin response, and inflammation,” they wrote. By replacing a serving of processed red meat, unprocessed red meat, or a combination of the two with a serving of dry fruit or legumes, the risk of developing diabetes is lowered by 30%, 41%, and 29%, respectively. Replacing red meat with a serving of dairy products is also associated with a reduced risk.

Confirmation

Several biological mechanisms could contribute to the increased risk for type 2 diabetes in people who consume red meat. The high level of saturated fats or the relatively low level of polyunsaturated fats, heme iron, or the high nitrate content in processed red meats could play a role. A strong positive association between consumption of this meat, particularly when processed, and the onset of diabetes has already emerged from other studies, including a trial carried out several years ago in the same cohorts. “In the current study, we wanted to look at this association in the same three cohorts in more detail, with over 9,000 additional cases of type 2 diabetes documented with extensive follow-up,” the researchers explained.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Excess consumption of red meat, whether processed or not, is linked to a greater risk for developing type 2 diabetes. This association was confirmed by a new study published in the American Journal of Clinical Nutrition, a data analysis of nearly 217,000 people who were monitored for three decades as part of several cohort studies. “Our study supports the current dietary recommendations of limiting consumption of red meat and highlights the importance of different alternative sources of protein in preventing type 2 diabetes,” the researchers wrote.

Consumption and risk

The study included men and women who took part in the Nurses’ Health Study, the Nurses’ Health Study II, or the Health Professionals Follow-up Study. Questionnaires were used to collect data every 2-4 years on the frequency of specific food consumption. Information on the onset of diseases and on different health-related aspects was collected every 2 years.

Those who consumed more red meat had a higher body mass index, higher total energy intake, and greater likelihood of being a smoker. They were physically less active and less likely to take multivitamins. In a follow-up of 5.48 million person-years, 22,761 cases of type 2 diabetes were recorded.

The link between consumption of processed and unprocessed red meat (and both combined) and a higher risk of diabetes was observed in all cohorts when analyzed separately and jointly. The people in the highest quintile for combined red meat consumption had a 2% greater risk of developing the disease, compared with those in the lowest quintile. The risk increases associated with processed and unprocessed meat were 51% and 40%, respectively. One additional serving per day of processed red meat was associated with a 1.46-fold greater risk of diabetes. This risk was 1.24 times greater for unprocessed meat and 1.28 times greater for both types combined.

The associations had a linear dose-response relationship and remained firm even after accounting for BMI, which the researchers stressed could be a mediating factor. Finally, the associations were stronger when considering the average cumulative consumption over the 30-year follow-up period and still stronger following the calibration of meat consumption with data extrapolated from food registers. The latter step was taken to account for measurement errors.
 

Alternatives are better

By analyzing alternative protein sources, the researchers discovered that nuts and legumes are associated with the most substantial reductions in diabetes risk. “This discovery is consistent with the evidence that shows that sources of unsaturated fatty acids and antioxidants have beneficial effects on glycemic control, insulin response, and inflammation,” they wrote. By replacing a serving of processed red meat, unprocessed red meat, or a combination of the two with a serving of dry fruit or legumes, the risk of developing diabetes is lowered by 30%, 41%, and 29%, respectively. Replacing red meat with a serving of dairy products is also associated with a reduced risk.

Confirmation

Several biological mechanisms could contribute to the increased risk for type 2 diabetes in people who consume red meat. The high level of saturated fats or the relatively low level of polyunsaturated fats, heme iron, or the high nitrate content in processed red meats could play a role. A strong positive association between consumption of this meat, particularly when processed, and the onset of diabetes has already emerged from other studies, including a trial carried out several years ago in the same cohorts. “In the current study, we wanted to look at this association in the same three cohorts in more detail, with over 9,000 additional cases of type 2 diabetes documented with extensive follow-up,” the researchers explained.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

I cock my head at my “new” patient, Sherri, who heads into my consultation room at 8:30 on a rainy Monday morning. She looks vaguely familiar but I can’t quite place her face. “Dr. Messer,” she cries, “don’t you remember me? I was one of your very first patients 15 years ago in Westchester. You had just finished training.” Suddenly it all comes back to me.

Meeting Sherri reminded me of the lesson in humility that my mentor, Dr. Alice Levine, taught our crowded lecture hall so many years ago. Once upon a time, she prided herself on being an infinitely important doctor. One day, she met a patient with empty sella syndrome (literally missing his whole pituitary gland – MRI proven). She fully expected to swoop in to save the patient’s life by expertly replacing each absconded pituitary hormone, but to her shock and delight, an invisible little sliver of pituitary left in his brain allowed him to magically eek out completely normal hormone levels.

Sherri walked into my office so many years ago with a body mass index in the mid-40s. In laymen’s terms, she was morbidly obese. I settled in to discuss her hypertension, diabetes, high cholesterol, fatty liver, polycystic ovary syndrome, etc., but to my shock and delight, her blood pressure and blood work were completely normal. I struggled to keep a neutral face. She was there to discuss hair loss. I had just met my first patient with metabolically healthy obesity (MHO), and I was floored.

Fast-forward 15 years. Sherri sits down across the desk from me and hands me her blood work. Her formerly pristine labs are now peppered with red exclamation points and critically high lab values. Sherri had transitioned from MHO to metabolically unhealthy obesity (MUO).

Early clinical trials concluded that it was possible to have obesity but be metabolically healthy. Approximately 15% of patients living with obesity lack any of the comorbidities typically associated with this phenotype. These findings contributed to the de-emphasis on obesity as a true disease state.

In retrospect, the MHO subtype appears to be much more common in the younger and more active population and is typically quite transient. A new study published in Diabetes, Obesity and Metabolism revealed that people with MHO are 1.5 times more likely to develop diabetes vs. metabolically healthy normal-weight individuals. In addition, people living with obesity and no known metabolic complications still had a 50% higher risk for coronary artery disease. The study also showed that over 50% of people initially characterized as MHO eventually became MUO after a 16-year follow-up.

So once again, all roads lead to semaglutide (Wegovy), the most effective U.S. Food and Drug Administration–approved weight loss medication to date. The incretin class of medications not only helps patients lose 15% or more of their body weight, but it also helps reverse insulin resistance, lower the risk for heart disease, melt away fatty liver, and lower cholesterol levels and blood pressures. While an emphasis on lifestyle changes is always important, these medications are critical adjuncts to conventional therapies.

Sherri’s nearly inevitable transition from MHO to MUO speaks to the pressing need to treat patients living with obesity before the metabolic complications and increased cardiovascular risk develop. Fifteen years ago, I discussed her hair loss for 45 minutes and never mentioned the looming issue. Of course, back then there was no semaglutide or tirzepatide, which was just approved for obesity.

Sherri left our most recent visit with a prescription for Wegovy as well as appointments with a complimentary trainer and dietitian. Now that we have the tools we need, let’s commit to helping our patients achieve true metabolic health. Unlike the magical pituitary patient, metabolically healthy obesity is an illusion – and we owe it to our patients to treat it as such.

Dr. Messer is a clinical assistant professor at Mount Sinai School of Medicine, New York, and an associate professor at Hofstra University, Hempstead, N.Y. She disclosed no relevant conflicts of interest.

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

I cock my head at my “new” patient, Sherri, who heads into my consultation room at 8:30 on a rainy Monday morning. She looks vaguely familiar but I can’t quite place her face. “Dr. Messer,” she cries, “don’t you remember me? I was one of your very first patients 15 years ago in Westchester. You had just finished training.” Suddenly it all comes back to me.

Meeting Sherri reminded me of the lesson in humility that my mentor, Dr. Alice Levine, taught our crowded lecture hall so many years ago. Once upon a time, she prided herself on being an infinitely important doctor. One day, she met a patient with empty sella syndrome (literally missing his whole pituitary gland – MRI proven). She fully expected to swoop in to save the patient’s life by expertly replacing each absconded pituitary hormone, but to her shock and delight, an invisible little sliver of pituitary left in his brain allowed him to magically eek out completely normal hormone levels.

Sherri walked into my office so many years ago with a body mass index in the mid-40s. In laymen’s terms, she was morbidly obese. I settled in to discuss her hypertension, diabetes, high cholesterol, fatty liver, polycystic ovary syndrome, etc., but to my shock and delight, her blood pressure and blood work were completely normal. I struggled to keep a neutral face. She was there to discuss hair loss. I had just met my first patient with metabolically healthy obesity (MHO), and I was floored.

Fast-forward 15 years. Sherri sits down across the desk from me and hands me her blood work. Her formerly pristine labs are now peppered with red exclamation points and critically high lab values. Sherri had transitioned from MHO to metabolically unhealthy obesity (MUO).

Early clinical trials concluded that it was possible to have obesity but be metabolically healthy. Approximately 15% of patients living with obesity lack any of the comorbidities typically associated with this phenotype. These findings contributed to the de-emphasis on obesity as a true disease state.

In retrospect, the MHO subtype appears to be much more common in the younger and more active population and is typically quite transient. A new study published in Diabetes, Obesity and Metabolism revealed that people with MHO are 1.5 times more likely to develop diabetes vs. metabolically healthy normal-weight individuals. In addition, people living with obesity and no known metabolic complications still had a 50% higher risk for coronary artery disease. The study also showed that over 50% of people initially characterized as MHO eventually became MUO after a 16-year follow-up.

So once again, all roads lead to semaglutide (Wegovy), the most effective U.S. Food and Drug Administration–approved weight loss medication to date. The incretin class of medications not only helps patients lose 15% or more of their body weight, but it also helps reverse insulin resistance, lower the risk for heart disease, melt away fatty liver, and lower cholesterol levels and blood pressures. While an emphasis on lifestyle changes is always important, these medications are critical adjuncts to conventional therapies.

Sherri’s nearly inevitable transition from MHO to MUO speaks to the pressing need to treat patients living with obesity before the metabolic complications and increased cardiovascular risk develop. Fifteen years ago, I discussed her hair loss for 45 minutes and never mentioned the looming issue. Of course, back then there was no semaglutide or tirzepatide, which was just approved for obesity.

Sherri left our most recent visit with a prescription for Wegovy as well as appointments with a complimentary trainer and dietitian. Now that we have the tools we need, let’s commit to helping our patients achieve true metabolic health. Unlike the magical pituitary patient, metabolically healthy obesity is an illusion – and we owe it to our patients to treat it as such.

Dr. Messer is a clinical assistant professor at Mount Sinai School of Medicine, New York, and an associate professor at Hofstra University, Hempstead, N.Y. She disclosed no relevant conflicts of interest.

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

I cock my head at my “new” patient, Sherri, who heads into my consultation room at 8:30 on a rainy Monday morning. She looks vaguely familiar but I can’t quite place her face. “Dr. Messer,” she cries, “don’t you remember me? I was one of your very first patients 15 years ago in Westchester. You had just finished training.” Suddenly it all comes back to me.

Meeting Sherri reminded me of the lesson in humility that my mentor, Dr. Alice Levine, taught our crowded lecture hall so many years ago. Once upon a time, she prided herself on being an infinitely important doctor. One day, she met a patient with empty sella syndrome (literally missing his whole pituitary gland – MRI proven). She fully expected to swoop in to save the patient’s life by expertly replacing each absconded pituitary hormone, but to her shock and delight, an invisible little sliver of pituitary left in his brain allowed him to magically eek out completely normal hormone levels.

Sherri walked into my office so many years ago with a body mass index in the mid-40s. In laymen’s terms, she was morbidly obese. I settled in to discuss her hypertension, diabetes, high cholesterol, fatty liver, polycystic ovary syndrome, etc., but to my shock and delight, her blood pressure and blood work were completely normal. I struggled to keep a neutral face. She was there to discuss hair loss. I had just met my first patient with metabolically healthy obesity (MHO), and I was floored.

Fast-forward 15 years. Sherri sits down across the desk from me and hands me her blood work. Her formerly pristine labs are now peppered with red exclamation points and critically high lab values. Sherri had transitioned from MHO to metabolically unhealthy obesity (MUO).

Early clinical trials concluded that it was possible to have obesity but be metabolically healthy. Approximately 15% of patients living with obesity lack any of the comorbidities typically associated with this phenotype. These findings contributed to the de-emphasis on obesity as a true disease state.

In retrospect, the MHO subtype appears to be much more common in the younger and more active population and is typically quite transient. A new study published in Diabetes, Obesity and Metabolism revealed that people with MHO are 1.5 times more likely to develop diabetes vs. metabolically healthy normal-weight individuals. In addition, people living with obesity and no known metabolic complications still had a 50% higher risk for coronary artery disease. The study also showed that over 50% of people initially characterized as MHO eventually became MUO after a 16-year follow-up.

So once again, all roads lead to semaglutide (Wegovy), the most effective U.S. Food and Drug Administration–approved weight loss medication to date. The incretin class of medications not only helps patients lose 15% or more of their body weight, but it also helps reverse insulin resistance, lower the risk for heart disease, melt away fatty liver, and lower cholesterol levels and blood pressures. While an emphasis on lifestyle changes is always important, these medications are critical adjuncts to conventional therapies.

Sherri’s nearly inevitable transition from MHO to MUO speaks to the pressing need to treat patients living with obesity before the metabolic complications and increased cardiovascular risk develop. Fifteen years ago, I discussed her hair loss for 45 minutes and never mentioned the looming issue. Of course, back then there was no semaglutide or tirzepatide, which was just approved for obesity.

Sherri left our most recent visit with a prescription for Wegovy as well as appointments with a complimentary trainer and dietitian. Now that we have the tools we need, let’s commit to helping our patients achieve true metabolic health. Unlike the magical pituitary patient, metabolically healthy obesity is an illusion – and we owe it to our patients to treat it as such.

Dr. Messer is a clinical assistant professor at Mount Sinai School of Medicine, New York, and an associate professor at Hofstra University, Hempstead, N.Y. She disclosed no relevant conflicts of interest.

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

Can too much of a healthy habit become bad? 

Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, very vigorous exercise may lead to these infections by triggering immune changes that increase risk, according to a new study.

The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be). 

Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.

But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.

“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”

That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel. 

The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear. 

After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts. 

“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
 

An adaptive mechanism gone awry

During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.

Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”

The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.

But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
 

Advice for patients

More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said. 

As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.  

“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.

And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
 

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

Can too much of a healthy habit become bad? 

Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, very vigorous exercise may lead to these infections by triggering immune changes that increase risk, according to a new study.

The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be). 

Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.

But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.

“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”

That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel. 

The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear. 

After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts. 

“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
 

An adaptive mechanism gone awry

During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.

Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”

The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.

But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
 

Advice for patients

More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said. 

As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.  

“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.

And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
 

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

Can too much of a healthy habit become bad? 

Lots of evidence shows that regular exercise wards off respiratory infections such as colds, flu, and COVID-19. However, very vigorous exercise may lead to these infections by triggering immune changes that increase risk, according to a new study.

The findings come as we enter another possible tripledemic this winter, with an increase in COVID, flu, and respiratory syncytial virus (RSV). Public health officials are on alert for a potentially severe flu season, following high flu activity this year in Australia (which can help predict how bad the U.S. flu season will be). 

Studies show that the risk for acute respiratory infections is lower in people who exercise regularly. Physically active people are also less likely to suffer severe outcomes from COVID.

But while inactivity has emerged as a potential risk factor for respiratory infections, scientists have long proposed that too much activity, particularly of a prolonged and highly intense nature, may also increase susceptibility.

“The theory suggests that a short-term suppression of the immune system following intense exercise leads to an increase in susceptibility to infection, especially upper respiratory illness,” said Choukri Ben Mamoun, PhD, professor of medicine (infectious diseases) and microbial pathogenesis at the Yale Institute for Global Health, New Haven, Conn. Researchers have documented a greater incidence of upper respiratory illness “among both highly trained and healthy untrained individuals following increased activity during competition or heaving training blocks.”

That’s important if you treat athletes or patients with physically demanding jobs that push them to their physical limits, such as firefighters, police officers, or military personnel. 

The new study was small but sheds light on a possible mechanism. Researchers tested blood, saliva, and urine samples from 11 firefighters before and 10 minutes after intense exercise designed to mimic wildfire fighting. The firefighters hiked over hilly terrain for 45 minutes in humid weather wearing up to 44 pounds of wildland gear. 

After the workout, subjects had fewer proinflammatory cytokines and ceramides, and more antimicrobial peptides, changes that indicate a greater susceptibility to infection, researchers said. A systematic review adds weight to their findings, revealing a handful of studies in marathon runners, firefighters, soldiers, and soccer players that found an increase in respiratory symptoms after strenuous workouts. 

“The relationship between exercise and the immune system is complex and varies from person to person,” said Dr. Mamoun, who was not part of the study. “Physicians can use this study’s findings to provide individualized exercise recommendations.”
 

An adaptive mechanism gone awry

During intense exercise, the body may reduce airway inflammation to help you breathe, say the authors. The boost in antimicrobial peptides found in the saliva samples could be the body’s way of compensating for the diminished immune function.

Antimicrobial peptides are part of the immune response but they’re “usually not very effective for viral infections,” said lead author Ernesto Nakayasu, PhD, senior research scientist at the Pacific Northwest National Laboratory, a U.S. Department of Energy lab in Richland, Washington. “That’s why we think it may make you more exposed to respiratory infections.”

The drop in proinflammatory molecules had an inverse relationship with opiorphin, a peripheral tissue vasodilator thought to increase blood flow and improve oxygen delivery to the muscles during exercise. This may be an adaptive mechanism to improve gas exchange in response to greater oxygen demand.

But as with many adaptive mechanisms, this one may have an unintended consequence. Fewer proinflammatory molecules on patrol may leave you more vulnerable to infection. Plus, during intense exercise, people tend to breathe through their mouths, bypassing the nasal barriers and allowing more microbes – including viruses – to penetrate and deposit in the distal airways of the lungs.
 

Advice for patients

More research is needed to know exactly how long and how strenuously one needs to exercise to trigger these immune changes, Dr. Nakayasu said. 

As shown by their lactate accumulation (an indicator of anaerobic metabolism), the firefighters in the study outpaced the average person’s aerobic respiratory capacity, meaning the average person doing moderate exercise likely wouldn’t trigger these changes.  

“Regular moderate exercise is generally associated with better health outcomes [and] improved immune function,” said Dr. Mamoun. For those who exercise to the extreme, proper rest and recovery are “essential for maintaining a robust immune system,” Dr. Mamoun said.

And of course, you can encourage patients to get vaccinated. Young, healthy patients may assume they don’t need COVID-19 or flu shots, as indicated by a recent survey that found one-third of Americans feel they don’t need these vaccinations if they’re not high risk.
 

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

Despite higher upfront costs, enhanced home blood pressure monitoring by hypertension patients could be cost-effective compared with standard clinical care over the longer term, a systematic review in JAMA Network Open found.

In an analysis of 16 studies, at-home blood pressure (HBPM) monitoring, particularly using automatic 24-hour continuous measurements alone or combined with additional support or team-based care, appeared to be economical over a minimum 10-year period compared with usual care – higher expenditures for equipment and training notwithstanding.

Texas A&amp;M University

“Our findings suggest that clinicians, hospitals, health care systems, third-party payers, and other stakeholders should consider the long-term incremental benefits and improvements in patients’ blood pressure, quality of life, and reductions in adverse outcomes,” wrote Michelle A. Hayek, of the Population Informatics Lab, department of industrial and systems engineering, at Texas A&M University, College Station, Tex., and colleagues.

HBPM increased considerably during the COVID pandemic and is expected to increase further in the next decade, according to lead author Theodoros Giannouchos, PhD, MS, MPharm, assistant professor in the department of health policy and organization in the School of Public Health at the University of Alabama at Birmingham. “Because home blood pressure monitoring might add costs to insurers, patients, and the health care system – at least short term – we noticed a gap in the updated literature on whether this method is cost-effective relative to in-office monitoring. Hence, we conducted this review.”

University of Alabama at Birmingham

Six of the 16 studies were conducted in the United States and six in the United Kingdom; 14 used a health care insurance system perspective to determine costs. In nearly half, quality-adjusted life-years gained and cost per 1–mm Hg reduction in blood pressure were used as outcomes.

Self-monitoring included self measurements transmitted to health care professionals and involved either periodic readings, such as twice each morning and evening during the first week of every month, 3 times per week, or 24-hour ambulatory readings with a portable device every 20 or 30 minutes. Among studies comparing HBPM alone versus 24-hour ambulatory BP monitoring (ABPM) or HBPM combined with additional support or team-based care, the latter two approaches were more cost effective. The benefits would appear to offset the costs of more resource-intensive at-home self-monitoring methods over office care and traditional at-home monitoring only.

In addition, the authors noted, ABPM in particular might detect elevated in-office, or white-coat hypertension, and masked hypertension, the latter referring to normal BP readings measured in the office but actual elevated pressures in the everyday home setting. An estimated 17.1 million adults in the United States have masked hypertension, and the authors say the new approach would allow early tailored interventions to mitigate the risk of masked hypertension or prevent unnecessary treatment because of white-coat hypertension. “Because of the growing market in blood pressure monitors, the technology and accuracy of monitors is expected to improve even more,” Dr. Giannouchos said. “If these technologies are properly used, they can improve patients’ quality of life and health outcomes at a justified level of cost.”

The findings align with previous research that synthesized costs and benefits of self-monitoring methods across various diseases and settings.

“Future work is needed to compare these alternatives directly from a cost-effectiveness standpoint and to provide clinicians, stakeholders, and patients with more evidence to prioritize specific home-based BP programs,” the authors wrote.

This research was supported by the Texas A&M President’s Office X-grant initiative, National Science Foundation PATHS-UP, and Population Informatics Lab. A study coauthor reported grants from National Science Foundation during the conduct of the study.

Despite higher upfront costs, enhanced home blood pressure monitoring by hypertension patients could be cost-effective compared with standard clinical care over the longer term, a systematic review in JAMA Network Open found.

In an analysis of 16 studies, at-home blood pressure (HBPM) monitoring, particularly using automatic 24-hour continuous measurements alone or combined with additional support or team-based care, appeared to be economical over a minimum 10-year period compared with usual care – higher expenditures for equipment and training notwithstanding.

Texas A&amp;M University

“Our findings suggest that clinicians, hospitals, health care systems, third-party payers, and other stakeholders should consider the long-term incremental benefits and improvements in patients’ blood pressure, quality of life, and reductions in adverse outcomes,” wrote Michelle A. Hayek, of the Population Informatics Lab, department of industrial and systems engineering, at Texas A&M University, College Station, Tex., and colleagues.

HBPM increased considerably during the COVID pandemic and is expected to increase further in the next decade, according to lead author Theodoros Giannouchos, PhD, MS, MPharm, assistant professor in the department of health policy and organization in the School of Public Health at the University of Alabama at Birmingham. “Because home blood pressure monitoring might add costs to insurers, patients, and the health care system – at least short term – we noticed a gap in the updated literature on whether this method is cost-effective relative to in-office monitoring. Hence, we conducted this review.”

University of Alabama at Birmingham

Six of the 16 studies were conducted in the United States and six in the United Kingdom; 14 used a health care insurance system perspective to determine costs. In nearly half, quality-adjusted life-years gained and cost per 1–mm Hg reduction in blood pressure were used as outcomes.

Self-monitoring included self measurements transmitted to health care professionals and involved either periodic readings, such as twice each morning and evening during the first week of every month, 3 times per week, or 24-hour ambulatory readings with a portable device every 20 or 30 minutes. Among studies comparing HBPM alone versus 24-hour ambulatory BP monitoring (ABPM) or HBPM combined with additional support or team-based care, the latter two approaches were more cost effective. The benefits would appear to offset the costs of more resource-intensive at-home self-monitoring methods over office care and traditional at-home monitoring only.

In addition, the authors noted, ABPM in particular might detect elevated in-office, or white-coat hypertension, and masked hypertension, the latter referring to normal BP readings measured in the office but actual elevated pressures in the everyday home setting. An estimated 17.1 million adults in the United States have masked hypertension, and the authors say the new approach would allow early tailored interventions to mitigate the risk of masked hypertension or prevent unnecessary treatment because of white-coat hypertension. “Because of the growing market in blood pressure monitors, the technology and accuracy of monitors is expected to improve even more,” Dr. Giannouchos said. “If these technologies are properly used, they can improve patients’ quality of life and health outcomes at a justified level of cost.”

The findings align with previous research that synthesized costs and benefits of self-monitoring methods across various diseases and settings.

“Future work is needed to compare these alternatives directly from a cost-effectiveness standpoint and to provide clinicians, stakeholders, and patients with more evidence to prioritize specific home-based BP programs,” the authors wrote.

This research was supported by the Texas A&M President’s Office X-grant initiative, National Science Foundation PATHS-UP, and Population Informatics Lab. A study coauthor reported grants from National Science Foundation during the conduct of the study.

Despite higher upfront costs, enhanced home blood pressure monitoring by hypertension patients could be cost-effective compared with standard clinical care over the longer term, a systematic review in JAMA Network Open found.

In an analysis of 16 studies, at-home blood pressure (HBPM) monitoring, particularly using automatic 24-hour continuous measurements alone or combined with additional support or team-based care, appeared to be economical over a minimum 10-year period compared with usual care – higher expenditures for equipment and training notwithstanding.

Texas A&amp;M University

“Our findings suggest that clinicians, hospitals, health care systems, third-party payers, and other stakeholders should consider the long-term incremental benefits and improvements in patients’ blood pressure, quality of life, and reductions in adverse outcomes,” wrote Michelle A. Hayek, of the Population Informatics Lab, department of industrial and systems engineering, at Texas A&M University, College Station, Tex., and colleagues.

HBPM increased considerably during the COVID pandemic and is expected to increase further in the next decade, according to lead author Theodoros Giannouchos, PhD, MS, MPharm, assistant professor in the department of health policy and organization in the School of Public Health at the University of Alabama at Birmingham. “Because home blood pressure monitoring might add costs to insurers, patients, and the health care system – at least short term – we noticed a gap in the updated literature on whether this method is cost-effective relative to in-office monitoring. Hence, we conducted this review.”

University of Alabama at Birmingham

Six of the 16 studies were conducted in the United States and six in the United Kingdom; 14 used a health care insurance system perspective to determine costs. In nearly half, quality-adjusted life-years gained and cost per 1–mm Hg reduction in blood pressure were used as outcomes.

Self-monitoring included self measurements transmitted to health care professionals and involved either periodic readings, such as twice each morning and evening during the first week of every month, 3 times per week, or 24-hour ambulatory readings with a portable device every 20 or 30 minutes. Among studies comparing HBPM alone versus 24-hour ambulatory BP monitoring (ABPM) or HBPM combined with additional support or team-based care, the latter two approaches were more cost effective. The benefits would appear to offset the costs of more resource-intensive at-home self-monitoring methods over office care and traditional at-home monitoring only.

In addition, the authors noted, ABPM in particular might detect elevated in-office, or white-coat hypertension, and masked hypertension, the latter referring to normal BP readings measured in the office but actual elevated pressures in the everyday home setting. An estimated 17.1 million adults in the United States have masked hypertension, and the authors say the new approach would allow early tailored interventions to mitigate the risk of masked hypertension or prevent unnecessary treatment because of white-coat hypertension. “Because of the growing market in blood pressure monitors, the technology and accuracy of monitors is expected to improve even more,” Dr. Giannouchos said. “If these technologies are properly used, they can improve patients’ quality of life and health outcomes at a justified level of cost.”

The findings align with previous research that synthesized costs and benefits of self-monitoring methods across various diseases and settings.

“Future work is needed to compare these alternatives directly from a cost-effectiveness standpoint and to provide clinicians, stakeholders, and patients with more evidence to prioritize specific home-based BP programs,” the authors wrote.

This research was supported by the Texas A&M President’s Office X-grant initiative, National Science Foundation PATHS-UP, and Population Informatics Lab. A study coauthor reported grants from National Science Foundation during the conduct of the study.

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

Glucagonlike peptide–1 receptor agonists (GLP-1 RAs), used for diabetes or obesity, are associated with a significantly lower quality of bowel preparation and a greater need for repeat colonoscopy, new research suggests.

“We began observing inadequate bowel preparation in our patients undergoing colonoscopy who were on GLP-1 RAs, which raised questions, especially given the association between these medications and delays in intestinal transit,” study investigator Eric. J. Vargas, MD, of the Mayo Clinic, Rochester, Minn., told this news organization. The team decided to investigate.

The “most surprising finding” was the “notably higher rate of inadequate bowel preparation, which necessitates a repeat colonoscopy within 12 months to ensure adequate screening and surveillance for colorectal cancers,” he said. “Specifically, for every 14 patients treated with GLP-1 RAs, one patient would require a repeat colonoscopy due to suboptimal preparation.”

In light of the findings, “clinicians should consider patients on GLP-1 RAs to be a population at risk for poor quality of bowel preparation,” he said.

The study was published online in the American Journal of Gastroenterology.
 

Low prep scores

The investigators analyzed a cohort of patients who underwent screening or surveillance colonoscopy at Mayo Clinic between 2021 and 2022. Patients taking any GLP-1 RA for diabetes or obesity at the time of colonoscopy were defined as “cases,” and those who were prescribed a GLP-1 RA at one point but had not taken it within 3 months of colonoscopy were controls.

The Boston Bowel Preparation Scale (BBPS) was used to assess bowel preparation quality.

The study included 446 patients: 265 (59%) taking a GLP-1 RA and 181 controls (41%). Overall, the average age was 59 years, about 54% were women, and 91% were White. Among those taking a GLP-1 RA, 86% had diabetes, as did 74% of controls.

Of patients on a GLP-1 RA, 48.8% took subcutaneous semaglutide, 3.1% took oral semaglutide, 34.6% took dulaglutide, 11% took liraglutide, and very small percentages took tirzepatide or exenatide.

There were no statistically significant differences between groups at baseline except for the diabetes diagnosis.

After diabetes was controlled for, the mean BBPS was significantly higher in controls than in GLP-1 RA recipients (7.5 vs. 7), and the percentage of patients with a total BBPS score less than 5 was significantly higher in the GLP-1 RA group than in the control group (15.5% vs. 6.6%).

In a secondary analysis of those with diabetes, the proportion of patients with a BBPS score less than or equal to 1 in any segment was higher in those taking a GLP-1 RA than in controls (24.9% vs. 13.3%).

The proportion of patients who required a repeat colonoscopy owing to inadequate bowel prep was higher among those taking a GLP-1 RA than among controls (18.9% vs. 11.1%). This corresponded to a number needed to harm of 14.

“GLP-1 RAs are increasingly used for the treatment of diabetes and obesity and have been demonstrated to reduce gastrointestinal motility,” the authors write. “Our data signal that the use of these medications in this patient population may be an additional factor in suboptimal bowel preparation.”

Limitations include the retrospective nature of the study, its focus on a single health system with a large majority of non-Hispanic White patients, and lack of data on diabetic complications and the use of insulin – all of which “necessitate caution in interpreting the findings,” the authors write.
 

Research ‘evolving rapidly’

“We will continue gathering more information on colonoscopy preparations and GLP-1 RA medication use, and whether the newer type 2 diabetes medications have a similar effect,” Dr. Vargas said. “The newer and upcoming medications are double and/or triple agonists, and it remains to be determined if these have a similar effect on gastric transit times.”

The recent lowering of the recommended colorectal cancer screening age for average-risk individuals to 45 combined with increasing use of GLP-1 RAs make it important to minimize repeat colonoscopies, he added.

“In the absence of specific guidance on timing of periprocedural discontinuation of GLP-1 RAs, clinicians can enhance counseling and educational efforts in this population,” Dr. Vargas suggested. They can also consider interventions such as “extending bowel preparation regimens, issuing a clear liquid diet recommendation 48-72 hours before colonoscopy, and nurse education visits on colonoscopy preparation.”

Commenting on the study, David A. Greenwald, MD, director of clinical gastroenterology and endoscopy at Mount Sinai Hospital, New York City, noted the potential confounding in a retrospective study, as well as the relatively small sample size. “Nonetheless, the findings make sense and are important to guide clinical decision-making,” he told this news organization.

Gastric emptying with GLP-1 RAs can lead to retained fluid and food in the stomach, which increase the risk for aspiration at endoscopy, he said.

“We are concerned about that primarily for upper endoscopy but have seen vomiting and aspiration occur during colonoscopy in patients who have been using [these] medications,” Dr. Greenwald said. It’s reasonable to postulate that GLP-1 RAs could delay passage of colonoscopy preps through the gastrointestinal tract, which would affect the outcome of prep, he added.

“Research around GLP-1 agonist use and endoscopy is evolving rapidly, and we hope to have data-driven guidance soon on whether these agents need to be held in the peri-endoscopic period, and if so, for how long,” Dr. Greenwald noted. “At the moment, guidance has been published but is very much driven by expert opinion and limited studies.”

The study received no financial support. Dr. Vargas and Dr. Greenwald report no relevant conflicts of interest.

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

Intensive lowering of blood pressure to a systolic target less than 120 mm Hg reduced cardiovascular events among individuals at high risk for cardiovascular disease, compared with standard treatment using a target less than 140 mm Hg in the ESPRIT trial.

“Intensive blood pressure–lowering treatment targeting a systolic pressure below 120 mm Hg for 3 years resulted in a 12% lower incidence of major vascular events, a 39% lower cardiovascular mortality, and 21% lower all-cause mortality than the standard treatment targeting a systolic pressure below 140 mm Hg,” reported lead investigator, Jing Li, MD, PhD, director of the department of preventive medicine at the National Center for Cardiovascular Diseases in Beijing.

The trial included patients with diabetes and those with a history of stroke, two important groups that were excluded in the previous SPRINT trial of intensive BP lowering. Results suggested that the benefit of intensive BP lowering extends to these groups.

The results translate into the prevention of 14 major vascular events and 8 deaths for every 1,000 individuals are treated for 3 years to a target systolic pressure less than 120 mm Hg rather than less than 140 mm Hg, at the cost of an additional three patients experiencing the serious adverse event of syncope, Dr. Li said.

“Our study generates new evidence about benefit and safety of treatment targeting systolic blood pressure below 120 mm Hg among a diverse Asian population, which is generally consistent with those from other ethnicities. Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide,” she concluded.

Dr. Li presented the ESPRIT trial at the annual scientific sessions of the American Heart Association.

The ESPRIT trial included 11,255 Chinese adults (average age, 64 years; 41% women) who had a baseline systolic BP measurement of 130-180 mm Hg (average was 147/83 mm Hg) and either established cardiovascular disease or at least two major risk factors for cardiovascular disease. Of those enrolled, 39% had diabetes, and 27% had a history of stroke.

They were randomly assigned to receive intensive BP treatment, with a systolic BP target less than 120 mm Hg, or standard treatment, with a target measurement less than 140 mm Hg, over a 3-year period. After 1 year, systolic pressure was lowered to 135.6 mm Hg in the standard care group and to 120.3 mm Hg in the intensive treatment group, with values remaining at around the same level for the remainder of the follow-up.

The primary outcome was a composite of myocardial infarction, coronary or noncoronary revascularization, hospitalization/ED visit for heart failure, stroke, or cardiovascular death.

After 3.4 years of follow-up, 624 primary outcome events had occurred in the standard arm (3.6%) versus 547 events in intensive arm (3.2%), a reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.78-0.99). This gives a number needed to treat to prevent one event of 74.

Cardiovascular death occurred in 0.5% of the standard group versus 0.3% of the intensive group (HR 0.61; 95% CI, 0.44-0.84); and all-cause death occurred in 1.1% of the standard group versus 0.9% of the intensive group (HR, 0.79; 95% CI, 0.64-0.97).

The individual endpoints of MI, stroke, and heart failure showed positive trends to a reduction with intensive BP lowering, but these did not reach statistical significance.

In terms of serious adverse events, syncope was increased in the intensive group (0.4% vs 0.1%), but there were no significant differences in hypotension, electrolyte abnormality, falls resulting in an injury, acute kidney injury, or renal failure.
 

Should 120 mm Hg be new target?

Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, said that the results were consistent with several other trials.  

“When we look at meta-analysis of trials of different levels of blood pressure reduction, all the studies show the same thing – the lower the blood pressure, the better the outcome, with those starting at higher levels gaining the greatest the benefit of blood pressure reductions,” he noted.

“There are four trials that have looked at systolic targets of less than 120 mm Hg versus less than 140 mm Hg (SPRINT, ACCORD BP, RESPECT, and now ESPRIT), and when analyzed properly, they all show a similar benefit for cardiovascular outcomes with the lower 120 target,” said Dr. Whelton, who led the SPRINT trial. 

“ESPRIT is a nicely done trial. It is reassuring because it is consistent with the other trials, in that it seems that the benefits are much greater than the risk of adverse effects,” he added.

Dr. Whelton pointed out that there are three more trials to come looking at this question, two in Brazil (one in individuals with diabetes and one in stroke survivors) and another trial in China in people with diabetes. “So, we will get more information from these.”

He said that guidelines committees will have to consider a lower systolic BP of 120 mm Hg as the optimal treatment target. In the United States, at present, the target is 130 mm Hg.

The current U.S. guidelines were based on the SPRINT trial, which showed a reduction in cardiovascular events in patients treated to a systolic target of 120 mm Hg versus 140 mm Hg.

Dr. Whelton, who was chair of the 2017 American College of Cardiology/American Heart Association hypertension guidelines committee, explained that, at the time the guidelines were written, there was only one trial, SPRINT, to base the evidence on.

“The committee could all comfortably agree on the 130 mm Hg target, but it was felt that there wasn’t enough evidence at the time to make a recommendation for 120 mm Hg,” he said. “But now we have four trials.”

He said that the trials included patients with high risk for cardiovascular disease, but they all brought some differences to the table, with ACCORD BP conducted in patients with diabetes; SPRINT having enrichment with African American patients, older adults, and patients with kidney disease; RESPECT was in stroke survivors; and ESPRIT had a mix of Chinese patients.

“I think we’ve got a nice mix of different participants and they’re all showing the same signal – that 120 mm Hg is better,” Dr. Whelton said.

But he stressed that although there is now good evidence in favor of lower BP targets, these findings were not being implemented in clinical practice.

“We are doing very badly in terms of implementation. There is a big gap between science and what’s happening in the real world.”

Dr. Whelton pointed out that only 30% of patients in high-income countries are controlled to the 140/90 target and that in low- and middle-income countries, only 8.8% get to that level, never mind lower targets. “The next job is to work on implementing these findings.”

He noted that several studies have shown better results in this regard using a team approach, with nonphysicians playing a major role in following up with patients.

A version of this article appeared on Medscape.com.

Intensive lowering of blood pressure to a systolic target less than 120 mm Hg reduced cardiovascular events among individuals at high risk for cardiovascular disease, compared with standard treatment using a target less than 140 mm Hg in the ESPRIT trial.

“Intensive blood pressure–lowering treatment targeting a systolic pressure below 120 mm Hg for 3 years resulted in a 12% lower incidence of major vascular events, a 39% lower cardiovascular mortality, and 21% lower all-cause mortality than the standard treatment targeting a systolic pressure below 140 mm Hg,” reported lead investigator, Jing Li, MD, PhD, director of the department of preventive medicine at the National Center for Cardiovascular Diseases in Beijing.

The trial included patients with diabetes and those with a history of stroke, two important groups that were excluded in the previous SPRINT trial of intensive BP lowering. Results suggested that the benefit of intensive BP lowering extends to these groups.

The results translate into the prevention of 14 major vascular events and 8 deaths for every 1,000 individuals are treated for 3 years to a target systolic pressure less than 120 mm Hg rather than less than 140 mm Hg, at the cost of an additional three patients experiencing the serious adverse event of syncope, Dr. Li said.

“Our study generates new evidence about benefit and safety of treatment targeting systolic blood pressure below 120 mm Hg among a diverse Asian population, which is generally consistent with those from other ethnicities. Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide,” she concluded.

Dr. Li presented the ESPRIT trial at the annual scientific sessions of the American Heart Association.

The ESPRIT trial included 11,255 Chinese adults (average age, 64 years; 41% women) who had a baseline systolic BP measurement of 130-180 mm Hg (average was 147/83 mm Hg) and either established cardiovascular disease or at least two major risk factors for cardiovascular disease. Of those enrolled, 39% had diabetes, and 27% had a history of stroke.

They were randomly assigned to receive intensive BP treatment, with a systolic BP target less than 120 mm Hg, or standard treatment, with a target measurement less than 140 mm Hg, over a 3-year period. After 1 year, systolic pressure was lowered to 135.6 mm Hg in the standard care group and to 120.3 mm Hg in the intensive treatment group, with values remaining at around the same level for the remainder of the follow-up.

The primary outcome was a composite of myocardial infarction, coronary or noncoronary revascularization, hospitalization/ED visit for heart failure, stroke, or cardiovascular death.

After 3.4 years of follow-up, 624 primary outcome events had occurred in the standard arm (3.6%) versus 547 events in intensive arm (3.2%), a reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.78-0.99). This gives a number needed to treat to prevent one event of 74.

Cardiovascular death occurred in 0.5% of the standard group versus 0.3% of the intensive group (HR 0.61; 95% CI, 0.44-0.84); and all-cause death occurred in 1.1% of the standard group versus 0.9% of the intensive group (HR, 0.79; 95% CI, 0.64-0.97).

The individual endpoints of MI, stroke, and heart failure showed positive trends to a reduction with intensive BP lowering, but these did not reach statistical significance.

In terms of serious adverse events, syncope was increased in the intensive group (0.4% vs 0.1%), but there were no significant differences in hypotension, electrolyte abnormality, falls resulting in an injury, acute kidney injury, or renal failure.
 

Should 120 mm Hg be new target?

Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, said that the results were consistent with several other trials.  

“When we look at meta-analysis of trials of different levels of blood pressure reduction, all the studies show the same thing – the lower the blood pressure, the better the outcome, with those starting at higher levels gaining the greatest the benefit of blood pressure reductions,” he noted.

“There are four trials that have looked at systolic targets of less than 120 mm Hg versus less than 140 mm Hg (SPRINT, ACCORD BP, RESPECT, and now ESPRIT), and when analyzed properly, they all show a similar benefit for cardiovascular outcomes with the lower 120 target,” said Dr. Whelton, who led the SPRINT trial. 

“ESPRIT is a nicely done trial. It is reassuring because it is consistent with the other trials, in that it seems that the benefits are much greater than the risk of adverse effects,” he added.

Dr. Whelton pointed out that there are three more trials to come looking at this question, two in Brazil (one in individuals with diabetes and one in stroke survivors) and another trial in China in people with diabetes. “So, we will get more information from these.”

He said that guidelines committees will have to consider a lower systolic BP of 120 mm Hg as the optimal treatment target. In the United States, at present, the target is 130 mm Hg.

The current U.S. guidelines were based on the SPRINT trial, which showed a reduction in cardiovascular events in patients treated to a systolic target of 120 mm Hg versus 140 mm Hg.

Dr. Whelton, who was chair of the 2017 American College of Cardiology/American Heart Association hypertension guidelines committee, explained that, at the time the guidelines were written, there was only one trial, SPRINT, to base the evidence on.

“The committee could all comfortably agree on the 130 mm Hg target, but it was felt that there wasn’t enough evidence at the time to make a recommendation for 120 mm Hg,” he said. “But now we have four trials.”

He said that the trials included patients with high risk for cardiovascular disease, but they all brought some differences to the table, with ACCORD BP conducted in patients with diabetes; SPRINT having enrichment with African American patients, older adults, and patients with kidney disease; RESPECT was in stroke survivors; and ESPRIT had a mix of Chinese patients.

“I think we’ve got a nice mix of different participants and they’re all showing the same signal – that 120 mm Hg is better,” Dr. Whelton said.

But he stressed that although there is now good evidence in favor of lower BP targets, these findings were not being implemented in clinical practice.

“We are doing very badly in terms of implementation. There is a big gap between science and what’s happening in the real world.”

Dr. Whelton pointed out that only 30% of patients in high-income countries are controlled to the 140/90 target and that in low- and middle-income countries, only 8.8% get to that level, never mind lower targets. “The next job is to work on implementing these findings.”

He noted that several studies have shown better results in this regard using a team approach, with nonphysicians playing a major role in following up with patients.

A version of this article appeared on Medscape.com.

Intensive lowering of blood pressure to a systolic target less than 120 mm Hg reduced cardiovascular events among individuals at high risk for cardiovascular disease, compared with standard treatment using a target less than 140 mm Hg in the ESPRIT trial.

“Intensive blood pressure–lowering treatment targeting a systolic pressure below 120 mm Hg for 3 years resulted in a 12% lower incidence of major vascular events, a 39% lower cardiovascular mortality, and 21% lower all-cause mortality than the standard treatment targeting a systolic pressure below 140 mm Hg,” reported lead investigator, Jing Li, MD, PhD, director of the department of preventive medicine at the National Center for Cardiovascular Diseases in Beijing.

The trial included patients with diabetes and those with a history of stroke, two important groups that were excluded in the previous SPRINT trial of intensive BP lowering. Results suggested that the benefit of intensive BP lowering extends to these groups.

The results translate into the prevention of 14 major vascular events and 8 deaths for every 1,000 individuals are treated for 3 years to a target systolic pressure less than 120 mm Hg rather than less than 140 mm Hg, at the cost of an additional three patients experiencing the serious adverse event of syncope, Dr. Li said.

“Our study generates new evidence about benefit and safety of treatment targeting systolic blood pressure below 120 mm Hg among a diverse Asian population, which is generally consistent with those from other ethnicities. Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide,” she concluded.

Dr. Li presented the ESPRIT trial at the annual scientific sessions of the American Heart Association.

The ESPRIT trial included 11,255 Chinese adults (average age, 64 years; 41% women) who had a baseline systolic BP measurement of 130-180 mm Hg (average was 147/83 mm Hg) and either established cardiovascular disease or at least two major risk factors for cardiovascular disease. Of those enrolled, 39% had diabetes, and 27% had a history of stroke.

They were randomly assigned to receive intensive BP treatment, with a systolic BP target less than 120 mm Hg, or standard treatment, with a target measurement less than 140 mm Hg, over a 3-year period. After 1 year, systolic pressure was lowered to 135.6 mm Hg in the standard care group and to 120.3 mm Hg in the intensive treatment group, with values remaining at around the same level for the remainder of the follow-up.

The primary outcome was a composite of myocardial infarction, coronary or noncoronary revascularization, hospitalization/ED visit for heart failure, stroke, or cardiovascular death.

After 3.4 years of follow-up, 624 primary outcome events had occurred in the standard arm (3.6%) versus 547 events in intensive arm (3.2%), a reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.78-0.99). This gives a number needed to treat to prevent one event of 74.

Cardiovascular death occurred in 0.5% of the standard group versus 0.3% of the intensive group (HR 0.61; 95% CI, 0.44-0.84); and all-cause death occurred in 1.1% of the standard group versus 0.9% of the intensive group (HR, 0.79; 95% CI, 0.64-0.97).

The individual endpoints of MI, stroke, and heart failure showed positive trends to a reduction with intensive BP lowering, but these did not reach statistical significance.

In terms of serious adverse events, syncope was increased in the intensive group (0.4% vs 0.1%), but there were no significant differences in hypotension, electrolyte abnormality, falls resulting in an injury, acute kidney injury, or renal failure.
 

Should 120 mm Hg be new target?

Commenting on the study, Paul Whelton, MD, chair in global public health at Tulane University, New Orleans, said that the results were consistent with several other trials.  

“When we look at meta-analysis of trials of different levels of blood pressure reduction, all the studies show the same thing – the lower the blood pressure, the better the outcome, with those starting at higher levels gaining the greatest the benefit of blood pressure reductions,” he noted.

“There are four trials that have looked at systolic targets of less than 120 mm Hg versus less than 140 mm Hg (SPRINT, ACCORD BP, RESPECT, and now ESPRIT), and when analyzed properly, they all show a similar benefit for cardiovascular outcomes with the lower 120 target,” said Dr. Whelton, who led the SPRINT trial. 

“ESPRIT is a nicely done trial. It is reassuring because it is consistent with the other trials, in that it seems that the benefits are much greater than the risk of adverse effects,” he added.

Dr. Whelton pointed out that there are three more trials to come looking at this question, two in Brazil (one in individuals with diabetes and one in stroke survivors) and another trial in China in people with diabetes. “So, we will get more information from these.”

He said that guidelines committees will have to consider a lower systolic BP of 120 mm Hg as the optimal treatment target. In the United States, at present, the target is 130 mm Hg.

The current U.S. guidelines were based on the SPRINT trial, which showed a reduction in cardiovascular events in patients treated to a systolic target of 120 mm Hg versus 140 mm Hg.

Dr. Whelton, who was chair of the 2017 American College of Cardiology/American Heart Association hypertension guidelines committee, explained that, at the time the guidelines were written, there was only one trial, SPRINT, to base the evidence on.

“The committee could all comfortably agree on the 130 mm Hg target, but it was felt that there wasn’t enough evidence at the time to make a recommendation for 120 mm Hg,” he said. “But now we have four trials.”

He said that the trials included patients with high risk for cardiovascular disease, but they all brought some differences to the table, with ACCORD BP conducted in patients with diabetes; SPRINT having enrichment with African American patients, older adults, and patients with kidney disease; RESPECT was in stroke survivors; and ESPRIT had a mix of Chinese patients.

“I think we’ve got a nice mix of different participants and they’re all showing the same signal – that 120 mm Hg is better,” Dr. Whelton said.

But he stressed that although there is now good evidence in favor of lower BP targets, these findings were not being implemented in clinical practice.

“We are doing very badly in terms of implementation. There is a big gap between science and what’s happening in the real world.”

Dr. Whelton pointed out that only 30% of patients in high-income countries are controlled to the 140/90 target and that in low- and middle-income countries, only 8.8% get to that level, never mind lower targets. “The next job is to work on implementing these findings.”

He noted that several studies have shown better results in this regard using a team approach, with nonphysicians playing a major role in following up with patients.

A version of this article appeared on Medscape.com.

TOPLINE:

Omega-3 polyunsaturated fatty acids reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) by lowering betacellulin (BTC), a protein growth factor that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.

METHODOLOGY:

• Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
• They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.

TAKEAWAY:

• BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
• BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
• By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.

IN PRACTICE:

“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”

SOURCE:

The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online  in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).

LIMITATIONS:

The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.

DISCLOSURES:

This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Omega-3 polyunsaturated fatty acids reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) by lowering betacellulin (BTC), a protein growth factor that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.

METHODOLOGY:

• Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
• They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.

TAKEAWAY:

• BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
• BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
• By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.

IN PRACTICE:

“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”

SOURCE:

The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online  in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).

LIMITATIONS:

The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.

DISCLOSURES:

This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Omega-3 polyunsaturated fatty acids reduce hepatic dysfunction in nonalcoholic steatohepatitis (NASH) by lowering betacellulin (BTC), a protein growth factor that contributes to liver fibrosis and progression to cirrhosis and liver cancer, new data suggest.

METHODOLOGY:

• Because omega-3 polyunsaturated fatty acids have been shown to reduce hepatic dysfunction in NASH, but the molecular underpinnings of this action were elusive, researchers conducted a multiomic network analysis applied to a mouse model of Western diet–induced NASH to identify the key mechanisms involved.
• They also performed a meta-analysis of human liver cancer transcriptome data to evaluate which aspects of NASH pathogenesis leading to cancer are reversed by omega-3 polyunsaturated fatty acids.

TAKEAWAY:

• BTC, an epidermal growth factor–binding protein, was consistently upregulated in liver cancer and downregulated by omega-3 polyunsaturated fatty acids in mice and humans with NASH.
• BTC promotes NASH fibrosis by activating dormant hepatic stellate cells to produce transforming growth factor beta-2 and increase collagen production. It also exacerbates toll-like receptor-dependent inflammatory processes in NASH.
• By downregulating BTC, omega-3 polyunsaturated fatty acids have therapeutic potential in NASH and could serve as a novel drug target.

IN PRACTICE:

“BTC represents a candidate master regulator inducing two most important factors (collagens and integrins) contributing to liver fibrosis and consequently promoting liver cancer,” the researchers write. “Future studies should investigate if BTC-triggered gene expression signatures can serve as biomarkers guiding personalized [omega-3 polyunsaturated fatty acid] therapy, as targets of new NAFLD/NASH drugs, and finally as a predictors of hepatic cancer risk in humans.”

SOURCE:

The study, with lead first author Jyothi Padiadpu, PhD, Oregon State University College of Pharmacy, Corvallis, was published online  in EMBO Molecular Medicine (2023. doi: 10.15252/emmm.202318367).

LIMITATIONS:

The study authors report no limitations. However, the findings are based on mouse model and human transcriptome data.

DISCLOSURES:

This research was supported by the National Institute of Diabetes and Digestive Kidney Diseases and the U.S. Department of Agriculture. The authors report no conflicts of interest.

A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved Medtronic’s Symplicity Spyral renal denervation system for the treatment of hypertension, the company has announced.

The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.

Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.

As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.

The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.

The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.

The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.

The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.

“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.

“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.

Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.

In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.

Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.

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

The Food and Drug Administration has approved Medtronic’s Symplicity Spyral renal denervation system for the treatment of hypertension, the company has announced.

The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.

Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.

As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.

The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.

The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.

The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.

The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.

“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.

“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.

Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.

In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.

Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.

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

The Food and Drug Administration has approved Medtronic’s Symplicity Spyral renal denervation system for the treatment of hypertension, the company has announced.

The Symplicity Spyral system, also known as the Symplicity blood pressure procedure, provides a catheter-based approach to denervate the renal arteries using radiofrequency energy.

Back in August, the FDA’s Circulatory System Devices Panel unanimously agreed that the Symplicity Spyral system is safe, but the panel was split on its efficacy and whether the benefits outweighed the risks associated with its use.

As part of the Medtronic SPYRAL HTN Global Clinical Program, more than 25,000 patients have been treated worldwide, both in the presence and absence of medication, and in patients with high baseline cardiovascular risk.

The SPYRAL HTN-OFF study enrolled patients with hypertension whose medications could be stopped at the start of the trial.

The primary effectiveness endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure (ASBP) from baseline to 3 months after renal denervation or sham procedure. The study showed a statistically significant reduction of 3.9 mm Hg ASBP in patients who received the device, compared with sham-control patients.

The SPYRAL HTN-ON study evaluated patients with uncontrolled hypertension who continued taking their BP medications during treatment with either the Spyral renal denervation device or a sham device.

The primary endpoint was the mean difference in the baseline adjusted 24-hour ambulatory systolic blood pressure at 6 months. The study showed a nonsignificant 24-hour 0.03 mm Hg reduction in ASBP in active-treatment patients, compared with sham-control patients.

“The Symplicity blood pressure procedure is safe and effective, providing significant ‘always-on’ blood pressure reductions for patients,” David Kandzari, MD, chief, Piedmont Heart Institute, Atlanta, and co–principal investigator of the SPYRAL clinical program, said in the news release.

“This approval paves the way for a transformation in hypertension treatment, offering a solution that complements medication and lifestyle changes,” added co–principal investigator Raymond Townsend, MD, with University of Pennsylvania, Philadelphia.

Medtronic notes that patient preference and shared decision-making are key components when considering the Symplicity blood pressure procedure.

In a patient preference study led by Medtronic, when presented with an interventional treatment with BP reduction and potential risks in line with those of the Symplicity blood pressure procedure, approximately one-third of patients were likely to choose the interventional treatment.

Earlier in November, the FDA also approved the Paradise Ultrasound Renal Denervation system (Recor Medical, Otsuka Medical Devices) for the treatment of hypertension.

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