News

If standard therapies don’t give relief to patients with refractory cough associated with interstitial lung disease, maybe a little poison could do the trick.

Among 41 patients with idiopathic interstitial pneumonia with autoimmune features (IPAFs) who had intractable cough, treatment with the traditional Chinese medicine semen strychni was associated with a significant improvement in patient-reported outcomes, reported Mingwan Su, MD, from Guang’anmen Hospital and the China Academy of Chinese Medical Sciences in Beijing, China.

“Semen strychni is associated with reduction in cough and can be an effective drug therapy for refractory cough in association with IPAFs,” she said in an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

Semen strychni is derived from the dried seeds of the plant Strychnos nux-vomica L. Its main toxic component is strychnine, the poison said to be favored by legendary mystery writer Agatha Christie.

Semen strychni is a central nervous system agonist that has reported efficacy in the treatment of musculoskeletal and autoimmune conditions, including rheumatoid arthritis, myasthenia gravis, and amyotrophic lateral sclerosis.

The medication also has immunomodulatory properties, Su said, and is thought to have beneficial effects against cough associated with IPAFs by reducing hypersensitivity.
 

Case-Control Study

To test this, Su and colleagues conducted a single-center retrospective study of the effects of semen strychni on 41 patients with IPAF-associated cough who were treated with low-dose oral semen strychni 300 mg/d for 2 weeks. These patients were paired with 41 control individuals matched for age, sex, and disease course. Control individuals received standard of care therapies.

The investigators found that for the primary endpoint of a change in the visual analog scale (VAS) at 2 weeks, there was a significantly greater reduction from baseline among patients treated with semen strychni compared with control individuals, with a baseline mean VAS score of 4.9 reduced to 2.1 at the end of treatment, vs 4.6 pre- to 3.3 post-treatment for control individuals. This difference translated to an odds ratio (OR) favoring semen strychni of 0.75 (P < .001).

In addition, the toxic compound was also associated with greater patient-reported improvement in the quality of life, as measured using the Leicester Cough Questionnaire, a 19-item scale that measures quality of life for people with chronic cough. Patients in the experimental arm had mean scores of 11.9 before treatment and 19 at the end of therapy compared with 12 and 15.1 points, respectively, among individuals in the control arm. This translated to an OR of 3.8 (P < .001) for patients on semen strychni.

The toxin appeared to be generally safe. There were no reported cases of pain, fainting, or bleeding in either study group, although there was one case of muscle twitching in the semen strychni group, Su reported.

There is evidence to suggest that semen strychni may have a calming effect on cough through action in the STAT3 pathway, considered to be a promising therapeutic target for musculoskeletal conditions, Su noted.
 

Not Ready for Prime Time

“My feeling is that these kinds of abstracts are welcome, but this is far from reality at this point,” said Vijay Balasubramanian, MD, clinical professor of medicine and director of the Pulmonary Hypertension Program at the University of California San Francisco.

“We need some kind of a regulated way of understanding dose characteristics and pharmacokinetics, and so it should be followed by more systematic studies,” he said in an interview.

Both Balasubramanian and his co-moderator Andrew R. Berman, MD, director of the Division of Pulmonary and Critical Care Medicine and Allergy and Rheumatology at Rutgers Health New Jersey Medical School in Newark, New Jersey, said that they sympathize with clinicians and their patients who seek out unusual therapies such as semen strychni.

“It’s very frustrating to treat chronic cough, especially associated with fibrotic lung disease, and the extent to which researchers will go to find that one product that perhaps can make a difference is understandable,” Berman told this news organization.

Su did not report a study funding source. Su, Balasubramanian, and Berman reported no relevant financial relationships.

 

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

If standard therapies don’t give relief to patients with refractory cough associated with interstitial lung disease, maybe a little poison could do the trick.

Among 41 patients with idiopathic interstitial pneumonia with autoimmune features (IPAFs) who had intractable cough, treatment with the traditional Chinese medicine semen strychni was associated with a significant improvement in patient-reported outcomes, reported Mingwan Su, MD, from Guang’anmen Hospital and the China Academy of Chinese Medical Sciences in Beijing, China.

“Semen strychni is associated with reduction in cough and can be an effective drug therapy for refractory cough in association with IPAFs,” she said in an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

Semen strychni is derived from the dried seeds of the plant Strychnos nux-vomica L. Its main toxic component is strychnine, the poison said to be favored by legendary mystery writer Agatha Christie.

Semen strychni is a central nervous system agonist that has reported efficacy in the treatment of musculoskeletal and autoimmune conditions, including rheumatoid arthritis, myasthenia gravis, and amyotrophic lateral sclerosis.

The medication also has immunomodulatory properties, Su said, and is thought to have beneficial effects against cough associated with IPAFs by reducing hypersensitivity.
 

Case-Control Study

To test this, Su and colleagues conducted a single-center retrospective study of the effects of semen strychni on 41 patients with IPAF-associated cough who were treated with low-dose oral semen strychni 300 mg/d for 2 weeks. These patients were paired with 41 control individuals matched for age, sex, and disease course. Control individuals received standard of care therapies.

The investigators found that for the primary endpoint of a change in the visual analog scale (VAS) at 2 weeks, there was a significantly greater reduction from baseline among patients treated with semen strychni compared with control individuals, with a baseline mean VAS score of 4.9 reduced to 2.1 at the end of treatment, vs 4.6 pre- to 3.3 post-treatment for control individuals. This difference translated to an odds ratio (OR) favoring semen strychni of 0.75 (P < .001).

In addition, the toxic compound was also associated with greater patient-reported improvement in the quality of life, as measured using the Leicester Cough Questionnaire, a 19-item scale that measures quality of life for people with chronic cough. Patients in the experimental arm had mean scores of 11.9 before treatment and 19 at the end of therapy compared with 12 and 15.1 points, respectively, among individuals in the control arm. This translated to an OR of 3.8 (P < .001) for patients on semen strychni.

The toxin appeared to be generally safe. There were no reported cases of pain, fainting, or bleeding in either study group, although there was one case of muscle twitching in the semen strychni group, Su reported.

There is evidence to suggest that semen strychni may have a calming effect on cough through action in the STAT3 pathway, considered to be a promising therapeutic target for musculoskeletal conditions, Su noted.
 

Not Ready for Prime Time

“My feeling is that these kinds of abstracts are welcome, but this is far from reality at this point,” said Vijay Balasubramanian, MD, clinical professor of medicine and director of the Pulmonary Hypertension Program at the University of California San Francisco.

“We need some kind of a regulated way of understanding dose characteristics and pharmacokinetics, and so it should be followed by more systematic studies,” he said in an interview.

Both Balasubramanian and his co-moderator Andrew R. Berman, MD, director of the Division of Pulmonary and Critical Care Medicine and Allergy and Rheumatology at Rutgers Health New Jersey Medical School in Newark, New Jersey, said that they sympathize with clinicians and their patients who seek out unusual therapies such as semen strychni.

“It’s very frustrating to treat chronic cough, especially associated with fibrotic lung disease, and the extent to which researchers will go to find that one product that perhaps can make a difference is understandable,” Berman told this news organization.

Su did not report a study funding source. Su, Balasubramanian, and Berman reported no relevant financial relationships.

 

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

If standard therapies don’t give relief to patients with refractory cough associated with interstitial lung disease, maybe a little poison could do the trick.

Among 41 patients with idiopathic interstitial pneumonia with autoimmune features (IPAFs) who had intractable cough, treatment with the traditional Chinese medicine semen strychni was associated with a significant improvement in patient-reported outcomes, reported Mingwan Su, MD, from Guang’anmen Hospital and the China Academy of Chinese Medical Sciences in Beijing, China.

“Semen strychni is associated with reduction in cough and can be an effective drug therapy for refractory cough in association with IPAFs,” she said in an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

Semen strychni is derived from the dried seeds of the plant Strychnos nux-vomica L. Its main toxic component is strychnine, the poison said to be favored by legendary mystery writer Agatha Christie.

Semen strychni is a central nervous system agonist that has reported efficacy in the treatment of musculoskeletal and autoimmune conditions, including rheumatoid arthritis, myasthenia gravis, and amyotrophic lateral sclerosis.

The medication also has immunomodulatory properties, Su said, and is thought to have beneficial effects against cough associated with IPAFs by reducing hypersensitivity.
 

Case-Control Study

To test this, Su and colleagues conducted a single-center retrospective study of the effects of semen strychni on 41 patients with IPAF-associated cough who were treated with low-dose oral semen strychni 300 mg/d for 2 weeks. These patients were paired with 41 control individuals matched for age, sex, and disease course. Control individuals received standard of care therapies.

The investigators found that for the primary endpoint of a change in the visual analog scale (VAS) at 2 weeks, there was a significantly greater reduction from baseline among patients treated with semen strychni compared with control individuals, with a baseline mean VAS score of 4.9 reduced to 2.1 at the end of treatment, vs 4.6 pre- to 3.3 post-treatment for control individuals. This difference translated to an odds ratio (OR) favoring semen strychni of 0.75 (P < .001).

In addition, the toxic compound was also associated with greater patient-reported improvement in the quality of life, as measured using the Leicester Cough Questionnaire, a 19-item scale that measures quality of life for people with chronic cough. Patients in the experimental arm had mean scores of 11.9 before treatment and 19 at the end of therapy compared with 12 and 15.1 points, respectively, among individuals in the control arm. This translated to an OR of 3.8 (P < .001) for patients on semen strychni.

The toxin appeared to be generally safe. There were no reported cases of pain, fainting, or bleeding in either study group, although there was one case of muscle twitching in the semen strychni group, Su reported.

There is evidence to suggest that semen strychni may have a calming effect on cough through action in the STAT3 pathway, considered to be a promising therapeutic target for musculoskeletal conditions, Su noted.
 

Not Ready for Prime Time

“My feeling is that these kinds of abstracts are welcome, but this is far from reality at this point,” said Vijay Balasubramanian, MD, clinical professor of medicine and director of the Pulmonary Hypertension Program at the University of California San Francisco.

“We need some kind of a regulated way of understanding dose characteristics and pharmacokinetics, and so it should be followed by more systematic studies,” he said in an interview.

Both Balasubramanian and his co-moderator Andrew R. Berman, MD, director of the Division of Pulmonary and Critical Care Medicine and Allergy and Rheumatology at Rutgers Health New Jersey Medical School in Newark, New Jersey, said that they sympathize with clinicians and their patients who seek out unusual therapies such as semen strychni.

“It’s very frustrating to treat chronic cough, especially associated with fibrotic lung disease, and the extent to which researchers will go to find that one product that perhaps can make a difference is understandable,” Berman told this news organization.

Su did not report a study funding source. Su, Balasubramanian, and Berman reported no relevant financial relationships.

 

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

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

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

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

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

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

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

When she was 5 years old, Katherine Edson, LCSW, tried to end her life by drowning herself. “I was enduring severe physical and sexual abuse, and it had become unbearable,” she said. “I waded into a lake, knowing there was a point when it would become too deep and I’d go under.”

As she was walking toward the deeper water, it occurred to her that if she died, she wouldn’t be able to eat Rice Krispies again. “I thought, ‘no more Snap, Crackle, and Pop’ — the three little mascots on the cereal box — and I felt sad,” said Edson, a New York–based retired therapist. “But I still kept walking.”

A man on the shore saw her disappear under the water and pulled her out. “I remember vomiting a lot of water and I remember that the man had tattoos, but I don’t remember how I felt to be alive. I was just numb.”

Edson thinks there were clues her pediatrician missed. “We lived in a small Southern town. Everyone knew my parents were alcoholics. I was very dissociated and withdrawn in general and during pediatric visits. My affect broadcasted that something was wrong, but no one asked if I was okay.”

She acknowledged that professionals in those days “weren’t tuned in to mental health issues in kids. At least there’s more awareness today and hopefully more training — especially since it seems like more kids are trying to end their lives today than when I was growing up.”
 

Alarming Statistics

According to the American Academy of Pediatrics (AAP), suicide is the second leading cause of death for people aged 10-24 years. Data from Children’s Hospital Association’s Pediatric Health Information System revealed that suicide attempts, ideation, and self-injury have become the most common mental health conditions seen in the emergency departments (EDs) of children’s hospitals, with a 166% increase in ED visits for suicide attempts in children aged 5-18 years, between 2016 and 2022.

Psychiatrist Helen Egger, MD, chief medical officer and co-founder of Little Otter, a specialty pediatric and whole family digital mental health company, recently coauthored a report analyzing data on 1434 children who completed a screening session and comprehensive diagnostic assessment at Little Otter from May 2023 to February 2024 (n = 1016 children aged 8-14 years and n = 418 aged 3-7 years).

Little Otter

Points of Contact

“It’s known that most children who die by suicide had a recent visit with a health professional — a pediatrician or child mental health professional. It’s unlikely that the child was fine and then, a few weeks later, stopped being fine. The likelihood is that the child wasn’t fine during that visit, but the clinician didn’t ask about mental health,” Egger said.

Christine Crawford, MD, MPH, associate medical director of the National Alliance on Mental Illness (NAMI), said that awareness of pediatric and adolescent suicidality is relevant to all physicians who treat children. “When you’re working with kids, anything can come up. Be prepared to navigate the conversation. You can never predict who the patient will feel most comfortable disclosing these thoughts to.”

NAMI

Don’t Be Afraid to Ask

According to the AAP, all children aged 12 years or older should be screened for suicidal risk, and children aged 8-11 years should be screened “when clinically indicated.” AAP also recommends annual screening for depression in children aged 12 years or older. However, Egger thinks that screening for depression should start sooner.

Katherine Kay Greydanus

It can be tempting to screen by merely giving a youngster a form to fill out in the waiting room, but Greydanus strongly advises against this approach. “The important thing is having rapport with the child, being in the same room together. You can ask some simple questions. ‘How are you doing? How are things at school? How are things with your family?’”

“When you’re screening for depression and have a kid who’s talking about sadness or low mood for more than 2 weeks and endorsing other symptoms, such as problems with sleep or appetite, difficulty concentrating, anhedonia, losing interest in things they’d usually enjoy, feeling they’re a burden to others, hopelessness about the future, being unable to function the way they used to — that person meets criteria for depression and you should have a high suspicion and concern about potential suicide,” said Crawford, assistant professor of psychiatry, Boston University School of Medicine.

She suggested probing further and being direct. “It sounds like you’ve been having a tough time. You talk about being sad. I wonder if you’re feeling so sad that you might not want to be alive anymore.” Some healthcare providers “tiptoe around when it comes to suicide, but it’s better to be direct and communicate the question in simple, plain language: ‘Have you ever had thoughts about hurting or killing yourself, that life is no longer worth living, or life would be easier for your family if you weren’t alive?’”

It’s a common myth that asking about depression or suicidality will “plant a seed” or “put ideas in people’s heads,” potentially leading to suicidality. “What we know to be true is that asking about suicide doesn’t put lives at risk. In fact, the contrary is true,” according to Crawford. Several studies have refuted this myth.

Two screening tools that might be helpful in ascertaining the presence of depression and suicidality are the PHQ-9 modified for Adolescents and the four-question Ask Suicide-Screening Questions.
 

Probe for More Details

If a child or adolescent affirms suicidal ideation, it’s important to ask if they have a plan, Crawford advised. “If they say, ‘yes,’ don’t run out of the office or shut down the conversation by picking up the phone and calling the closest child psychiatrist. We want kids to open up as much as possible when they’ve already opened up a little. So continue the conversation.”

If a child has a plan, the risk for following through on that plan is “high,” Crawford emphasized. “You want the maximum amount of information at your fingertips because this will equip you to navigate the next step in getting the child help.”

The suicide plan may not be realistic and, if carried out, might not actually end in death, especially in younger children. “A 6-year-old might say, ‘I’m gonna drink a whole bottle of apple juice and my belly will explode.’ Or ‘I’ll take 10 extra vitamins.’ The objective lethality of the plan doesn’t matter in that moment. What matters is that the child believes it’s going to work, and it provides a window into how depressed that child is.”

Greydanus added that it’s important to understand what might be going on in the child’s life. Could there be abuse in the family? Is the child being bullied? Bullying can take place at school or online, he noted. The overall risk for suicidal thoughts is elevated for youth who are involved in bullying, whether they’re the bully or the one being bullied.

Kirk Smalley, president and co-founder of Stand for the Silent, an organization designed to bring awareness about the devastating effects of bullying, agreed that pediatricians a should ask children if they’re being bullied. “Sometimes, kids will open up to someone who isn’t a parent or a teacher, who might be seen as ‘too close’ to the situation,” Smalley said.

“Let them know you’re a trusted adult they can confide in and you’re willing to help them navigate this — and then follow through,” advised Smalley, whose 11-year-old son died by suicide after being subjected to bullying.
 

Painting a Complete Picture

Crawford advises clinicians to “look at the whole picture and piece it together.”

For example, “if the child is functioning, going to school, maintaining relationships with other people, and not experiencing symptoms of depression but discloses the desire to kill him/herself, understand the context.” Sometimes, adolescents can be impulsive. Decision-making “can be driven by emotion.” The teen may have experienced emotional distress, such as “conflict with a peer, arguments with a parent, or romantic heartbreak. She might say, ‘I’m going to kill myself if I ever see him holding hands with another girl.’”

In the setting of an acute stressor, such as a breakup, the child might not need a higher level of care such as hospitalization. “But for non-psychiatry providers, it’s unclear if the child might act on it, so it’s important to have the child evaluated; talk to collateral supports, such as parents, teachers, or a therapist if they have one; and see what makes sense for that specific child.”

She also recommended “getting a sense if the kid is future-oriented in thinking. If they’re talking about an upcoming concert this weekend, or wanting to get to basketball practice, that’s reassuring. It suggests the likelihood of following through [on suicide] is low.”

And assess coping strategies. “You can say, ‘I see you’re really going through a lot. I worry that these thoughts will come up in school. What do you think you’d do in the moment if these thoughts come up?’ If there’s a coping strategy — for example, ‘I’d talk to my friend during lunch’ — that’s also reassuring,” Crawford said.

Of course, that doesn’t mean the statement should be ignored or dismissed. Rather, it informs the next preventive steps and how intensive the level of care should be.
 

Next Steps: Involving the Family, Getting Help

It’s particularly concerning if the child is unable to identify strategies other than suicide, said Crawford. “You can say, ‘I’m concerned because it’s highly likely that you’ll run into this guy and I wouldn’t want you to die. You have so much to live for.’”

Then, you can ask if it’s okay to bring in the parent or caregiver to talk about what the child just revealed. “If the kid says no — especially a teen — you can respond, ‘I hear what you’re saying, but I actually do have to bring your parent in because of your safety and we can discuss together how to keep you safe.’”

In advance, Crawford tells the patient what she plans to share with the parent. “That way, we’re on the same page and the kid has a sense of agency about how the conversation with the parent will go.” If the teen doesn’t want certain information revealed, “you can ask, ‘What would you leave out, and why?’ This lends itself to a helpful conversation about what the child is thinking about.”

Once the provider has received the green light, it’s time to bring the parent into the room. “Especially in the primary care or pediatric setting, the parent is often shocked, worried, and caught off-guard,” Crawford said.

“You can start by thanking the patient for being open and honest. Then you can tell the parent, ‘Your daughter shared she’s been having some difficult emotions and experiences, and she’s thought of ending her life because she doesn’t know how to cope. I wanted to talk to you about this because it’s important to look at resources we can connect her to and effective coping strategies.’”

Further interventions can include referring the patient to a child psychiatrist or therapist, or both. “Have a list of referrals readily available,” Greydanus advised. If you suspect or if the child reveals abuse, you’re a mandated reporter and need to inform Child Protective Services (CPS). “But don’t stop there,” he warned. “Make sure the child is indeed getting help through CPS and appropriate intervention has been taken regarding the abuse and potential suicide attempt.” Or you may send the child to the ED, where ED physicians are “trained in what to do if they suspect abuse. But make sure that when you ‘throw the ball,’ there’s someone who can ‘catch’ it and accept responsibility for the child’s safety.”

Crawford noted that many primary care settings — especially in under-resourced areas — lack child psychiatrists or therapists. “You need to know what’s feasible in the community you’re practicing in,” she advised. “Be aware of the local crisis line — 988 — and mental health resources in the school and community. There are often school psychologists, social workers, or counselors who can become involved.”

Greydanus emphasized that it’s critical to assess for the presence of firearms in the home and address it with the parents. “If a child is sad or angry and gets impulsive, it’s amazingly common for them to get their hands in a firearm and use it.”

As previously reported, pediatricians and other healthcare providers have a valuable role to play in screening parents for firearm ownership and offering counseling on safe storage practices, according to research presented on September 28 at the AAP 2024 National Conference.
 

Sometimes, Even the Best Efforts Aren’t Successful

“Suicide is complicated, and parents or doctors can take all the ‘right’ steps to get counseling for the child — hospitalization, medication, and support — and children might still take their lives,” said Ronnie Susan Walker, MS, LCPC, founder and executive director of Alliance of Hope for Suicide Loss Survivors. The organization was launched as a “postvention campaign” 7 years ago to provide support to survivors of suicide loss, who are themselves a high-risk population for suicide.

Walker alluded to the concept of a “ suicide trance” — a term coined by Richard Heckler, PhD, in his book Waking Up, Alive. This trance “is a state of mind and body that receives only the kind of input that reinforces the pain and corroborates the person’s conviction that the only way out is through death,” Heckler wrote.

Walker, whose stepson died by suicide, said physicians and other healthcare professionals who have lost a patient to suicide “should focus on postvention — finding support from other professionals and managing their own grief and guilt.”

It’s natural to feel guilt and second-guess yourself, Greydanus said. “You question whether you missed something or could have done more, so acknowledge that even with the best care and intentions, some suicides aren’t preventable,” he said.

Walker recommends reaching out to the family. “When I lost my stepson, his doctor came to the funeral and wrote us a very meaningful note. That meant so much to us.”

Greydanus agreed it’s appropriate for the clinician to offer comfort to the family “if he or she feels it necessary or feels moved to do so.” However, he cautioned, there’s “often a fear of malpractice charges that may interfere in certain cases.”

Egger added that records should always be “very detailed,” with clear documentation of how you interacted with the child and the rationale behind your interventions. “I’m not a legal expert, but I would always err on the side of connecting with family and sharing grief and compassion. My experience with physician-patient relationships is that the more connected, transparent, and empathetic they are, the better the outcome will be for everyone.”

Losing a patient to suicide is traumatic, so give yourself time to grieve, Egger advised. “Unfortunately, this is an experience that almost everyone in the field will likely go through at some point. Reach out for professional counseling or peer support.”

Physicians who have lost a patient to suicide may turn to an online forum, the Coalition of Clinician Survivors, designed to create a safe anonymous space for discussion, education, testimonials, and one-on-one support.

Greydanus emphasized that the most important role in working with suicidal youngsters is to provide hope. “Yes, you can’t help everyone, but you can help most of them. That’s why you’re there.”

Greydanus, Crawford, Egger, Edson, Smalley, and Walker reported no financial conflicts of interest.
 

A version of this article appeared on Medscape.com.

When she was 5 years old, Katherine Edson, LCSW, tried to end her life by drowning herself. “I was enduring severe physical and sexual abuse, and it had become unbearable,” she said. “I waded into a lake, knowing there was a point when it would become too deep and I’d go under.”

As she was walking toward the deeper water, it occurred to her that if she died, she wouldn’t be able to eat Rice Krispies again. “I thought, ‘no more Snap, Crackle, and Pop’ — the three little mascots on the cereal box — and I felt sad,” said Edson, a New York–based retired therapist. “But I still kept walking.”

A man on the shore saw her disappear under the water and pulled her out. “I remember vomiting a lot of water and I remember that the man had tattoos, but I don’t remember how I felt to be alive. I was just numb.”

Edson thinks there were clues her pediatrician missed. “We lived in a small Southern town. Everyone knew my parents were alcoholics. I was very dissociated and withdrawn in general and during pediatric visits. My affect broadcasted that something was wrong, but no one asked if I was okay.”

She acknowledged that professionals in those days “weren’t tuned in to mental health issues in kids. At least there’s more awareness today and hopefully more training — especially since it seems like more kids are trying to end their lives today than when I was growing up.”
 

Alarming Statistics

According to the American Academy of Pediatrics (AAP), suicide is the second leading cause of death for people aged 10-24 years. Data from Children’s Hospital Association’s Pediatric Health Information System revealed that suicide attempts, ideation, and self-injury have become the most common mental health conditions seen in the emergency departments (EDs) of children’s hospitals, with a 166% increase in ED visits for suicide attempts in children aged 5-18 years, between 2016 and 2022.

Psychiatrist Helen Egger, MD, chief medical officer and co-founder of Little Otter, a specialty pediatric and whole family digital mental health company, recently coauthored a report analyzing data on 1434 children who completed a screening session and comprehensive diagnostic assessment at Little Otter from May 2023 to February 2024 (n = 1016 children aged 8-14 years and n = 418 aged 3-7 years).

Little Otter

Points of Contact

“It’s known that most children who die by suicide had a recent visit with a health professional — a pediatrician or child mental health professional. It’s unlikely that the child was fine and then, a few weeks later, stopped being fine. The likelihood is that the child wasn’t fine during that visit, but the clinician didn’t ask about mental health,” Egger said.

Christine Crawford, MD, MPH, associate medical director of the National Alliance on Mental Illness (NAMI), said that awareness of pediatric and adolescent suicidality is relevant to all physicians who treat children. “When you’re working with kids, anything can come up. Be prepared to navigate the conversation. You can never predict who the patient will feel most comfortable disclosing these thoughts to.”

NAMI

Don’t Be Afraid to Ask

According to the AAP, all children aged 12 years or older should be screened for suicidal risk, and children aged 8-11 years should be screened “when clinically indicated.” AAP also recommends annual screening for depression in children aged 12 years or older. However, Egger thinks that screening for depression should start sooner.

Katherine Kay Greydanus

It can be tempting to screen by merely giving a youngster a form to fill out in the waiting room, but Greydanus strongly advises against this approach. “The important thing is having rapport with the child, being in the same room together. You can ask some simple questions. ‘How are you doing? How are things at school? How are things with your family?’”

“When you’re screening for depression and have a kid who’s talking about sadness or low mood for more than 2 weeks and endorsing other symptoms, such as problems with sleep or appetite, difficulty concentrating, anhedonia, losing interest in things they’d usually enjoy, feeling they’re a burden to others, hopelessness about the future, being unable to function the way they used to — that person meets criteria for depression and you should have a high suspicion and concern about potential suicide,” said Crawford, assistant professor of psychiatry, Boston University School of Medicine.

She suggested probing further and being direct. “It sounds like you’ve been having a tough time. You talk about being sad. I wonder if you’re feeling so sad that you might not want to be alive anymore.” Some healthcare providers “tiptoe around when it comes to suicide, but it’s better to be direct and communicate the question in simple, plain language: ‘Have you ever had thoughts about hurting or killing yourself, that life is no longer worth living, or life would be easier for your family if you weren’t alive?’”

It’s a common myth that asking about depression or suicidality will “plant a seed” or “put ideas in people’s heads,” potentially leading to suicidality. “What we know to be true is that asking about suicide doesn’t put lives at risk. In fact, the contrary is true,” according to Crawford. Several studies have refuted this myth.

Two screening tools that might be helpful in ascertaining the presence of depression and suicidality are the PHQ-9 modified for Adolescents and the four-question Ask Suicide-Screening Questions.
 

Probe for More Details

If a child or adolescent affirms suicidal ideation, it’s important to ask if they have a plan, Crawford advised. “If they say, ‘yes,’ don’t run out of the office or shut down the conversation by picking up the phone and calling the closest child psychiatrist. We want kids to open up as much as possible when they’ve already opened up a little. So continue the conversation.”

If a child has a plan, the risk for following through on that plan is “high,” Crawford emphasized. “You want the maximum amount of information at your fingertips because this will equip you to navigate the next step in getting the child help.”

The suicide plan may not be realistic and, if carried out, might not actually end in death, especially in younger children. “A 6-year-old might say, ‘I’m gonna drink a whole bottle of apple juice and my belly will explode.’ Or ‘I’ll take 10 extra vitamins.’ The objective lethality of the plan doesn’t matter in that moment. What matters is that the child believes it’s going to work, and it provides a window into how depressed that child is.”

Greydanus added that it’s important to understand what might be going on in the child’s life. Could there be abuse in the family? Is the child being bullied? Bullying can take place at school or online, he noted. The overall risk for suicidal thoughts is elevated for youth who are involved in bullying, whether they’re the bully or the one being bullied.

Kirk Smalley, president and co-founder of Stand for the Silent, an organization designed to bring awareness about the devastating effects of bullying, agreed that pediatricians a should ask children if they’re being bullied. “Sometimes, kids will open up to someone who isn’t a parent or a teacher, who might be seen as ‘too close’ to the situation,” Smalley said.

“Let them know you’re a trusted adult they can confide in and you’re willing to help them navigate this — and then follow through,” advised Smalley, whose 11-year-old son died by suicide after being subjected to bullying.
 

Painting a Complete Picture

Crawford advises clinicians to “look at the whole picture and piece it together.”

For example, “if the child is functioning, going to school, maintaining relationships with other people, and not experiencing symptoms of depression but discloses the desire to kill him/herself, understand the context.” Sometimes, adolescents can be impulsive. Decision-making “can be driven by emotion.” The teen may have experienced emotional distress, such as “conflict with a peer, arguments with a parent, or romantic heartbreak. She might say, ‘I’m going to kill myself if I ever see him holding hands with another girl.’”

In the setting of an acute stressor, such as a breakup, the child might not need a higher level of care such as hospitalization. “But for non-psychiatry providers, it’s unclear if the child might act on it, so it’s important to have the child evaluated; talk to collateral supports, such as parents, teachers, or a therapist if they have one; and see what makes sense for that specific child.”

She also recommended “getting a sense if the kid is future-oriented in thinking. If they’re talking about an upcoming concert this weekend, or wanting to get to basketball practice, that’s reassuring. It suggests the likelihood of following through [on suicide] is low.”

And assess coping strategies. “You can say, ‘I see you’re really going through a lot. I worry that these thoughts will come up in school. What do you think you’d do in the moment if these thoughts come up?’ If there’s a coping strategy — for example, ‘I’d talk to my friend during lunch’ — that’s also reassuring,” Crawford said.

Of course, that doesn’t mean the statement should be ignored or dismissed. Rather, it informs the next preventive steps and how intensive the level of care should be.
 

Next Steps: Involving the Family, Getting Help

It’s particularly concerning if the child is unable to identify strategies other than suicide, said Crawford. “You can say, ‘I’m concerned because it’s highly likely that you’ll run into this guy and I wouldn’t want you to die. You have so much to live for.’”

Then, you can ask if it’s okay to bring in the parent or caregiver to talk about what the child just revealed. “If the kid says no — especially a teen — you can respond, ‘I hear what you’re saying, but I actually do have to bring your parent in because of your safety and we can discuss together how to keep you safe.’”

In advance, Crawford tells the patient what she plans to share with the parent. “That way, we’re on the same page and the kid has a sense of agency about how the conversation with the parent will go.” If the teen doesn’t want certain information revealed, “you can ask, ‘What would you leave out, and why?’ This lends itself to a helpful conversation about what the child is thinking about.”

Once the provider has received the green light, it’s time to bring the parent into the room. “Especially in the primary care or pediatric setting, the parent is often shocked, worried, and caught off-guard,” Crawford said.

“You can start by thanking the patient for being open and honest. Then you can tell the parent, ‘Your daughter shared she’s been having some difficult emotions and experiences, and she’s thought of ending her life because she doesn’t know how to cope. I wanted to talk to you about this because it’s important to look at resources we can connect her to and effective coping strategies.’”

Further interventions can include referring the patient to a child psychiatrist or therapist, or both. “Have a list of referrals readily available,” Greydanus advised. If you suspect or if the child reveals abuse, you’re a mandated reporter and need to inform Child Protective Services (CPS). “But don’t stop there,” he warned. “Make sure the child is indeed getting help through CPS and appropriate intervention has been taken regarding the abuse and potential suicide attempt.” Or you may send the child to the ED, where ED physicians are “trained in what to do if they suspect abuse. But make sure that when you ‘throw the ball,’ there’s someone who can ‘catch’ it and accept responsibility for the child’s safety.”

Crawford noted that many primary care settings — especially in under-resourced areas — lack child psychiatrists or therapists. “You need to know what’s feasible in the community you’re practicing in,” she advised. “Be aware of the local crisis line — 988 — and mental health resources in the school and community. There are often school psychologists, social workers, or counselors who can become involved.”

Greydanus emphasized that it’s critical to assess for the presence of firearms in the home and address it with the parents. “If a child is sad or angry and gets impulsive, it’s amazingly common for them to get their hands in a firearm and use it.”

As previously reported, pediatricians and other healthcare providers have a valuable role to play in screening parents for firearm ownership and offering counseling on safe storage practices, according to research presented on September 28 at the AAP 2024 National Conference.
 

Sometimes, Even the Best Efforts Aren’t Successful

“Suicide is complicated, and parents or doctors can take all the ‘right’ steps to get counseling for the child — hospitalization, medication, and support — and children might still take their lives,” said Ronnie Susan Walker, MS, LCPC, founder and executive director of Alliance of Hope for Suicide Loss Survivors. The organization was launched as a “postvention campaign” 7 years ago to provide support to survivors of suicide loss, who are themselves a high-risk population for suicide.

Walker alluded to the concept of a “ suicide trance” — a term coined by Richard Heckler, PhD, in his book Waking Up, Alive. This trance “is a state of mind and body that receives only the kind of input that reinforces the pain and corroborates the person’s conviction that the only way out is through death,” Heckler wrote.

Walker, whose stepson died by suicide, said physicians and other healthcare professionals who have lost a patient to suicide “should focus on postvention — finding support from other professionals and managing their own grief and guilt.”

It’s natural to feel guilt and second-guess yourself, Greydanus said. “You question whether you missed something or could have done more, so acknowledge that even with the best care and intentions, some suicides aren’t preventable,” he said.

Walker recommends reaching out to the family. “When I lost my stepson, his doctor came to the funeral and wrote us a very meaningful note. That meant so much to us.”

Greydanus agreed it’s appropriate for the clinician to offer comfort to the family “if he or she feels it necessary or feels moved to do so.” However, he cautioned, there’s “often a fear of malpractice charges that may interfere in certain cases.”

Egger added that records should always be “very detailed,” with clear documentation of how you interacted with the child and the rationale behind your interventions. “I’m not a legal expert, but I would always err on the side of connecting with family and sharing grief and compassion. My experience with physician-patient relationships is that the more connected, transparent, and empathetic they are, the better the outcome will be for everyone.”

Losing a patient to suicide is traumatic, so give yourself time to grieve, Egger advised. “Unfortunately, this is an experience that almost everyone in the field will likely go through at some point. Reach out for professional counseling or peer support.”

Physicians who have lost a patient to suicide may turn to an online forum, the Coalition of Clinician Survivors, designed to create a safe anonymous space for discussion, education, testimonials, and one-on-one support.

Greydanus emphasized that the most important role in working with suicidal youngsters is to provide hope. “Yes, you can’t help everyone, but you can help most of them. That’s why you’re there.”

Greydanus, Crawford, Egger, Edson, Smalley, and Walker reported no financial conflicts of interest.
 

A version of this article appeared on Medscape.com.

When she was 5 years old, Katherine Edson, LCSW, tried to end her life by drowning herself. “I was enduring severe physical and sexual abuse, and it had become unbearable,” she said. “I waded into a lake, knowing there was a point when it would become too deep and I’d go under.”

As she was walking toward the deeper water, it occurred to her that if she died, she wouldn’t be able to eat Rice Krispies again. “I thought, ‘no more Snap, Crackle, and Pop’ — the three little mascots on the cereal box — and I felt sad,” said Edson, a New York–based retired therapist. “But I still kept walking.”

A man on the shore saw her disappear under the water and pulled her out. “I remember vomiting a lot of water and I remember that the man had tattoos, but I don’t remember how I felt to be alive. I was just numb.”

Edson thinks there were clues her pediatrician missed. “We lived in a small Southern town. Everyone knew my parents were alcoholics. I was very dissociated and withdrawn in general and during pediatric visits. My affect broadcasted that something was wrong, but no one asked if I was okay.”

She acknowledged that professionals in those days “weren’t tuned in to mental health issues in kids. At least there’s more awareness today and hopefully more training — especially since it seems like more kids are trying to end their lives today than when I was growing up.”
 

Alarming Statistics

According to the American Academy of Pediatrics (AAP), suicide is the second leading cause of death for people aged 10-24 years. Data from Children’s Hospital Association’s Pediatric Health Information System revealed that suicide attempts, ideation, and self-injury have become the most common mental health conditions seen in the emergency departments (EDs) of children’s hospitals, with a 166% increase in ED visits for suicide attempts in children aged 5-18 years, between 2016 and 2022.

Psychiatrist Helen Egger, MD, chief medical officer and co-founder of Little Otter, a specialty pediatric and whole family digital mental health company, recently coauthored a report analyzing data on 1434 children who completed a screening session and comprehensive diagnostic assessment at Little Otter from May 2023 to February 2024 (n = 1016 children aged 8-14 years and n = 418 aged 3-7 years).

Little Otter

Points of Contact

“It’s known that most children who die by suicide had a recent visit with a health professional — a pediatrician or child mental health professional. It’s unlikely that the child was fine and then, a few weeks later, stopped being fine. The likelihood is that the child wasn’t fine during that visit, but the clinician didn’t ask about mental health,” Egger said.

Christine Crawford, MD, MPH, associate medical director of the National Alliance on Mental Illness (NAMI), said that awareness of pediatric and adolescent suicidality is relevant to all physicians who treat children. “When you’re working with kids, anything can come up. Be prepared to navigate the conversation. You can never predict who the patient will feel most comfortable disclosing these thoughts to.”

NAMI

Don’t Be Afraid to Ask

According to the AAP, all children aged 12 years or older should be screened for suicidal risk, and children aged 8-11 years should be screened “when clinically indicated.” AAP also recommends annual screening for depression in children aged 12 years or older. However, Egger thinks that screening for depression should start sooner.

Katherine Kay Greydanus

It can be tempting to screen by merely giving a youngster a form to fill out in the waiting room, but Greydanus strongly advises against this approach. “The important thing is having rapport with the child, being in the same room together. You can ask some simple questions. ‘How are you doing? How are things at school? How are things with your family?’”

“When you’re screening for depression and have a kid who’s talking about sadness or low mood for more than 2 weeks and endorsing other symptoms, such as problems with sleep or appetite, difficulty concentrating, anhedonia, losing interest in things they’d usually enjoy, feeling they’re a burden to others, hopelessness about the future, being unable to function the way they used to — that person meets criteria for depression and you should have a high suspicion and concern about potential suicide,” said Crawford, assistant professor of psychiatry, Boston University School of Medicine.

She suggested probing further and being direct. “It sounds like you’ve been having a tough time. You talk about being sad. I wonder if you’re feeling so sad that you might not want to be alive anymore.” Some healthcare providers “tiptoe around when it comes to suicide, but it’s better to be direct and communicate the question in simple, plain language: ‘Have you ever had thoughts about hurting or killing yourself, that life is no longer worth living, or life would be easier for your family if you weren’t alive?’”

It’s a common myth that asking about depression or suicidality will “plant a seed” or “put ideas in people’s heads,” potentially leading to suicidality. “What we know to be true is that asking about suicide doesn’t put lives at risk. In fact, the contrary is true,” according to Crawford. Several studies have refuted this myth.

Two screening tools that might be helpful in ascertaining the presence of depression and suicidality are the PHQ-9 modified for Adolescents and the four-question Ask Suicide-Screening Questions.
 

Probe for More Details

If a child or adolescent affirms suicidal ideation, it’s important to ask if they have a plan, Crawford advised. “If they say, ‘yes,’ don’t run out of the office or shut down the conversation by picking up the phone and calling the closest child psychiatrist. We want kids to open up as much as possible when they’ve already opened up a little. So continue the conversation.”

If a child has a plan, the risk for following through on that plan is “high,” Crawford emphasized. “You want the maximum amount of information at your fingertips because this will equip you to navigate the next step in getting the child help.”

The suicide plan may not be realistic and, if carried out, might not actually end in death, especially in younger children. “A 6-year-old might say, ‘I’m gonna drink a whole bottle of apple juice and my belly will explode.’ Or ‘I’ll take 10 extra vitamins.’ The objective lethality of the plan doesn’t matter in that moment. What matters is that the child believes it’s going to work, and it provides a window into how depressed that child is.”

Greydanus added that it’s important to understand what might be going on in the child’s life. Could there be abuse in the family? Is the child being bullied? Bullying can take place at school or online, he noted. The overall risk for suicidal thoughts is elevated for youth who are involved in bullying, whether they’re the bully or the one being bullied.

Kirk Smalley, president and co-founder of Stand for the Silent, an organization designed to bring awareness about the devastating effects of bullying, agreed that pediatricians a should ask children if they’re being bullied. “Sometimes, kids will open up to someone who isn’t a parent or a teacher, who might be seen as ‘too close’ to the situation,” Smalley said.

“Let them know you’re a trusted adult they can confide in and you’re willing to help them navigate this — and then follow through,” advised Smalley, whose 11-year-old son died by suicide after being subjected to bullying.
 

Painting a Complete Picture

Crawford advises clinicians to “look at the whole picture and piece it together.”

For example, “if the child is functioning, going to school, maintaining relationships with other people, and not experiencing symptoms of depression but discloses the desire to kill him/herself, understand the context.” Sometimes, adolescents can be impulsive. Decision-making “can be driven by emotion.” The teen may have experienced emotional distress, such as “conflict with a peer, arguments with a parent, or romantic heartbreak. She might say, ‘I’m going to kill myself if I ever see him holding hands with another girl.’”

In the setting of an acute stressor, such as a breakup, the child might not need a higher level of care such as hospitalization. “But for non-psychiatry providers, it’s unclear if the child might act on it, so it’s important to have the child evaluated; talk to collateral supports, such as parents, teachers, or a therapist if they have one; and see what makes sense for that specific child.”

She also recommended “getting a sense if the kid is future-oriented in thinking. If they’re talking about an upcoming concert this weekend, or wanting to get to basketball practice, that’s reassuring. It suggests the likelihood of following through [on suicide] is low.”

And assess coping strategies. “You can say, ‘I see you’re really going through a lot. I worry that these thoughts will come up in school. What do you think you’d do in the moment if these thoughts come up?’ If there’s a coping strategy — for example, ‘I’d talk to my friend during lunch’ — that’s also reassuring,” Crawford said.

Of course, that doesn’t mean the statement should be ignored or dismissed. Rather, it informs the next preventive steps and how intensive the level of care should be.
 

Next Steps: Involving the Family, Getting Help

It’s particularly concerning if the child is unable to identify strategies other than suicide, said Crawford. “You can say, ‘I’m concerned because it’s highly likely that you’ll run into this guy and I wouldn’t want you to die. You have so much to live for.’”

Then, you can ask if it’s okay to bring in the parent or caregiver to talk about what the child just revealed. “If the kid says no — especially a teen — you can respond, ‘I hear what you’re saying, but I actually do have to bring your parent in because of your safety and we can discuss together how to keep you safe.’”

In advance, Crawford tells the patient what she plans to share with the parent. “That way, we’re on the same page and the kid has a sense of agency about how the conversation with the parent will go.” If the teen doesn’t want certain information revealed, “you can ask, ‘What would you leave out, and why?’ This lends itself to a helpful conversation about what the child is thinking about.”

Once the provider has received the green light, it’s time to bring the parent into the room. “Especially in the primary care or pediatric setting, the parent is often shocked, worried, and caught off-guard,” Crawford said.

“You can start by thanking the patient for being open and honest. Then you can tell the parent, ‘Your daughter shared she’s been having some difficult emotions and experiences, and she’s thought of ending her life because she doesn’t know how to cope. I wanted to talk to you about this because it’s important to look at resources we can connect her to and effective coping strategies.’”

Further interventions can include referring the patient to a child psychiatrist or therapist, or both. “Have a list of referrals readily available,” Greydanus advised. If you suspect or if the child reveals abuse, you’re a mandated reporter and need to inform Child Protective Services (CPS). “But don’t stop there,” he warned. “Make sure the child is indeed getting help through CPS and appropriate intervention has been taken regarding the abuse and potential suicide attempt.” Or you may send the child to the ED, where ED physicians are “trained in what to do if they suspect abuse. But make sure that when you ‘throw the ball,’ there’s someone who can ‘catch’ it and accept responsibility for the child’s safety.”

Crawford noted that many primary care settings — especially in under-resourced areas — lack child psychiatrists or therapists. “You need to know what’s feasible in the community you’re practicing in,” she advised. “Be aware of the local crisis line — 988 — and mental health resources in the school and community. There are often school psychologists, social workers, or counselors who can become involved.”

Greydanus emphasized that it’s critical to assess for the presence of firearms in the home and address it with the parents. “If a child is sad or angry and gets impulsive, it’s amazingly common for them to get their hands in a firearm and use it.”

As previously reported, pediatricians and other healthcare providers have a valuable role to play in screening parents for firearm ownership and offering counseling on safe storage practices, according to research presented on September 28 at the AAP 2024 National Conference.
 

Sometimes, Even the Best Efforts Aren’t Successful

“Suicide is complicated, and parents or doctors can take all the ‘right’ steps to get counseling for the child — hospitalization, medication, and support — and children might still take their lives,” said Ronnie Susan Walker, MS, LCPC, founder and executive director of Alliance of Hope for Suicide Loss Survivors. The organization was launched as a “postvention campaign” 7 years ago to provide support to survivors of suicide loss, who are themselves a high-risk population for suicide.

Walker alluded to the concept of a “ suicide trance” — a term coined by Richard Heckler, PhD, in his book Waking Up, Alive. This trance “is a state of mind and body that receives only the kind of input that reinforces the pain and corroborates the person’s conviction that the only way out is through death,” Heckler wrote.

Walker, whose stepson died by suicide, said physicians and other healthcare professionals who have lost a patient to suicide “should focus on postvention — finding support from other professionals and managing their own grief and guilt.”

It’s natural to feel guilt and second-guess yourself, Greydanus said. “You question whether you missed something or could have done more, so acknowledge that even with the best care and intentions, some suicides aren’t preventable,” he said.

Walker recommends reaching out to the family. “When I lost my stepson, his doctor came to the funeral and wrote us a very meaningful note. That meant so much to us.”

Greydanus agreed it’s appropriate for the clinician to offer comfort to the family “if he or she feels it necessary or feels moved to do so.” However, he cautioned, there’s “often a fear of malpractice charges that may interfere in certain cases.”

Egger added that records should always be “very detailed,” with clear documentation of how you interacted with the child and the rationale behind your interventions. “I’m not a legal expert, but I would always err on the side of connecting with family and sharing grief and compassion. My experience with physician-patient relationships is that the more connected, transparent, and empathetic they are, the better the outcome will be for everyone.”

Losing a patient to suicide is traumatic, so give yourself time to grieve, Egger advised. “Unfortunately, this is an experience that almost everyone in the field will likely go through at some point. Reach out for professional counseling or peer support.”

Physicians who have lost a patient to suicide may turn to an online forum, the Coalition of Clinician Survivors, designed to create a safe anonymous space for discussion, education, testimonials, and one-on-one support.

Greydanus emphasized that the most important role in working with suicidal youngsters is to provide hope. “Yes, you can’t help everyone, but you can help most of them. That’s why you’re there.”

Greydanus, Crawford, Egger, Edson, Smalley, and Walker reported no financial conflicts of interest.
 

A version of this article appeared on Medscape.com.

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

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

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

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

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

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

For people with severe symptomatic hip osteoarthritis, total hip replacement (THR) alleviates hip pain and improves function much more effectively than a resistance training program supervised by a physiotherapist, according to the results of a randomized controlled clinical trial. 

In the PROHIP study, the mean increases in Oxford Hip Scores from baseline to 6 months were 15.9 points for THR and 4.5 points for resistance training. The 11.4-point difference in scores was both statistically and clinically significant, the study’s investigators reported in The New England Journal of Medicine. 

“Our results are clear: Surgery is superior to exercise in patients who have hip osteoarthritis and indication for surgery, and now we have finally proven that with the highest level of evidence,” corresponding author Thomas Frydendal, PT, PhD, MSc, told this news organization.

Frydendal, who was involved in the study while working on his PhD at University Hospital of Southern Denmark – Lillebaelt Hospital, Vejle, Denmark, the primary center for the trial, is now a postdoctoral researcher at the Department of Clinical Medicine, Aarhus University, and Department of Orthopedic Surgery, Aarhus University Hospital.

“We believe that our findings are pretty robust,” Frydendal added. “I think if someone in the world conducts a trial similar to ours, they will find fairly close or consistent findings, no matter what type of exercise they choose.”

Charlotte Dahl, Lillebaelt Hospital–University Hospital of Southern Denmark, Vejle Hospital

The PROHIP Study

THR is routinely recommended for the management of severe hip osteoarthritis, but since there are no clinical trial data on the effectiveness of this procedure as compared with first-line treatment such as resistance training, the PROHIP study was conceived. 

The trial was conducted at four Danish orthopedic centers and designed as a superiority study, the hypothesis being that THR would be better at alleviating self-reported hip pain and improving hip function than resistance training. 

Of a possible 1474 individuals with a clinical suspicion of hip osteoarthritis, 791 were deemed eligible for inclusion in the trial. Inclusion criteria were being aged 50 years or older and having an indication for THR based on the presence of hip pain and clinical and radiographic findings.

However, the majority (86%) declined to enter the study, with almost half (43%) deciding to have a THR and enroll in a parallel observational cohort. This meant that only 110 (14%) individuals agreed to participate and underwent randomization, which does limit the study’s generalizability, the PROHIP investigators acknowledged. 
 

Design and Study Population

The change in Oxford Hip Score from baseline to 6 months was selected as the primary outcome measure based on the findings of a prior qualitative study. This 12-item, patient-reported outcome measure gives a score ranging from 0 to 48, with higher scores indicating less hip pain and better hip function. The estimated minimal clinically important difference is a change of 5 points. 

After a baseline assessment, 53 of 109 individuals were randomly assigned to undergo THR and 56 to participate in the resistance training program. Overall, the mean age of participants was 67.6 years, and half were women. The average duration of hip pain was a median of 1.7 years. 

The median time to receipt of the allocated treatment was 2.8 months in the THR group and 0.5 months in the resistance training group. 

Those allocated to the THR group also underwent a “fast track” program that involved patient education, pain management, and early mobilization. 

The resistance training group received 12 weeks of exercise supervised by a physiotherapist and then offered 12 weeks of additional exercise conducted on their own. The physiotherapist-supervised exercise sessions were held twice weekly and lasted for 1 hour. These started with a 10-minute warm-up on a stationary bike, followed by a standard set of resistance-based exercises that included a leg press, hip extension, hip flexion, and hip abduction. 
 

‘Reassuring’ Results

In a comment, consultant orthopedic surgeon Antony Palmer, MA, BMBCh, DPhil, said: “It’s reassuring that patients with advanced symptomatic osteoarthritis do well with hip replacements.”

THR does of course come with the potential risk for complications, but “the rate of these is what you’d expect for that procedure,” Palmer said, who works for the Nuffield Orthopaedic Centre, Oxford University Hospital NHS Foundation Trust, and is a senior clinical research fellow at Oxford University in England.

Dr. Palmer

Resistance Training Role 

A notable finding was that, at 6 months, five (9%) people assigned to the THR arm had not undergone surgery, and 12 (21%) people in the resistance training group had undergone a THR.

This could suggest two things, Palmer suggested in the interview. The first is that there could be a small proportion of people assigned to THR who may not need the operation and do well with exercise therapy. And, conversely, there may be those who would do well having the surgery without first going through the intermediate stage of physical therapy. 

It’s a suggestion that “maybe we’ve got to refine that a bit better and identify the patients that really do benefit from physiotherapy and who might not need hip replacement as a result,” Palmer said.

Or in other words, “should all patients undergo a program of physiotherapy before considering surgery?” he added.
 

Authors’ View

The PROHIP investigators conclude: “These results support current recommendations for the management of hip osteoarthritis and may be used to inform and guide shared decision making in clinical practice.”

Moreover, the results “do not oppose the use of resistance training as initial treatment,” says the authors. 

Frydendal highlighted in his interview that nearly three out of four of the patients reported not to have undertaken any type of supervised exercise before entry into the study, which is a first-line, guideline-recommended option.

“If a patient tells me, ‘I haven’t done any exercise previously,’ I’d recommend starting with completing a 6- to 12-week exercise program that is tailored to your individual needs and evaluate your symptoms afterward,” he said. 

“But we should refer the patient if our first-line treatment does not offer any improvements in the patient’s symptoms, as surgery with total hip replacement is clearly a really good treatment option,” Frydendal said.

The study was funded by the Danish Rheumatism Association, among other independent bodies. Frydendal and Palmer reported no relevant financial relationships. 
 

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

For people with severe symptomatic hip osteoarthritis, total hip replacement (THR) alleviates hip pain and improves function much more effectively than a resistance training program supervised by a physiotherapist, according to the results of a randomized controlled clinical trial. 

In the PROHIP study, the mean increases in Oxford Hip Scores from baseline to 6 months were 15.9 points for THR and 4.5 points for resistance training. The 11.4-point difference in scores was both statistically and clinically significant, the study’s investigators reported in The New England Journal of Medicine. 

“Our results are clear: Surgery is superior to exercise in patients who have hip osteoarthritis and indication for surgery, and now we have finally proven that with the highest level of evidence,” corresponding author Thomas Frydendal, PT, PhD, MSc, told this news organization.

Frydendal, who was involved in the study while working on his PhD at University Hospital of Southern Denmark – Lillebaelt Hospital, Vejle, Denmark, the primary center for the trial, is now a postdoctoral researcher at the Department of Clinical Medicine, Aarhus University, and Department of Orthopedic Surgery, Aarhus University Hospital.

“We believe that our findings are pretty robust,” Frydendal added. “I think if someone in the world conducts a trial similar to ours, they will find fairly close or consistent findings, no matter what type of exercise they choose.”

Charlotte Dahl, Lillebaelt Hospital–University Hospital of Southern Denmark, Vejle Hospital

The PROHIP Study

THR is routinely recommended for the management of severe hip osteoarthritis, but since there are no clinical trial data on the effectiveness of this procedure as compared with first-line treatment such as resistance training, the PROHIP study was conceived. 

The trial was conducted at four Danish orthopedic centers and designed as a superiority study, the hypothesis being that THR would be better at alleviating self-reported hip pain and improving hip function than resistance training. 

Of a possible 1474 individuals with a clinical suspicion of hip osteoarthritis, 791 were deemed eligible for inclusion in the trial. Inclusion criteria were being aged 50 years or older and having an indication for THR based on the presence of hip pain and clinical and radiographic findings.

However, the majority (86%) declined to enter the study, with almost half (43%) deciding to have a THR and enroll in a parallel observational cohort. This meant that only 110 (14%) individuals agreed to participate and underwent randomization, which does limit the study’s generalizability, the PROHIP investigators acknowledged. 
 

Design and Study Population

The change in Oxford Hip Score from baseline to 6 months was selected as the primary outcome measure based on the findings of a prior qualitative study. This 12-item, patient-reported outcome measure gives a score ranging from 0 to 48, with higher scores indicating less hip pain and better hip function. The estimated minimal clinically important difference is a change of 5 points. 

After a baseline assessment, 53 of 109 individuals were randomly assigned to undergo THR and 56 to participate in the resistance training program. Overall, the mean age of participants was 67.6 years, and half were women. The average duration of hip pain was a median of 1.7 years. 

The median time to receipt of the allocated treatment was 2.8 months in the THR group and 0.5 months in the resistance training group. 

Those allocated to the THR group also underwent a “fast track” program that involved patient education, pain management, and early mobilization. 

The resistance training group received 12 weeks of exercise supervised by a physiotherapist and then offered 12 weeks of additional exercise conducted on their own. The physiotherapist-supervised exercise sessions were held twice weekly and lasted for 1 hour. These started with a 10-minute warm-up on a stationary bike, followed by a standard set of resistance-based exercises that included a leg press, hip extension, hip flexion, and hip abduction. 
 

‘Reassuring’ Results

In a comment, consultant orthopedic surgeon Antony Palmer, MA, BMBCh, DPhil, said: “It’s reassuring that patients with advanced symptomatic osteoarthritis do well with hip replacements.”

THR does of course come with the potential risk for complications, but “the rate of these is what you’d expect for that procedure,” Palmer said, who works for the Nuffield Orthopaedic Centre, Oxford University Hospital NHS Foundation Trust, and is a senior clinical research fellow at Oxford University in England.

Dr. Palmer

Resistance Training Role 

A notable finding was that, at 6 months, five (9%) people assigned to the THR arm had not undergone surgery, and 12 (21%) people in the resistance training group had undergone a THR.

This could suggest two things, Palmer suggested in the interview. The first is that there could be a small proportion of people assigned to THR who may not need the operation and do well with exercise therapy. And, conversely, there may be those who would do well having the surgery without first going through the intermediate stage of physical therapy. 

It’s a suggestion that “maybe we’ve got to refine that a bit better and identify the patients that really do benefit from physiotherapy and who might not need hip replacement as a result,” Palmer said.

Or in other words, “should all patients undergo a program of physiotherapy before considering surgery?” he added.
 

Authors’ View

The PROHIP investigators conclude: “These results support current recommendations for the management of hip osteoarthritis and may be used to inform and guide shared decision making in clinical practice.”

Moreover, the results “do not oppose the use of resistance training as initial treatment,” says the authors. 

Frydendal highlighted in his interview that nearly three out of four of the patients reported not to have undertaken any type of supervised exercise before entry into the study, which is a first-line, guideline-recommended option.

“If a patient tells me, ‘I haven’t done any exercise previously,’ I’d recommend starting with completing a 6- to 12-week exercise program that is tailored to your individual needs and evaluate your symptoms afterward,” he said. 

“But we should refer the patient if our first-line treatment does not offer any improvements in the patient’s symptoms, as surgery with total hip replacement is clearly a really good treatment option,” Frydendal said.

The study was funded by the Danish Rheumatism Association, among other independent bodies. Frydendal and Palmer reported no relevant financial relationships. 
 

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

For people with severe symptomatic hip osteoarthritis, total hip replacement (THR) alleviates hip pain and improves function much more effectively than a resistance training program supervised by a physiotherapist, according to the results of a randomized controlled clinical trial. 

In the PROHIP study, the mean increases in Oxford Hip Scores from baseline to 6 months were 15.9 points for THR and 4.5 points for resistance training. The 11.4-point difference in scores was both statistically and clinically significant, the study’s investigators reported in The New England Journal of Medicine. 

“Our results are clear: Surgery is superior to exercise in patients who have hip osteoarthritis and indication for surgery, and now we have finally proven that with the highest level of evidence,” corresponding author Thomas Frydendal, PT, PhD, MSc, told this news organization.

Frydendal, who was involved in the study while working on his PhD at University Hospital of Southern Denmark – Lillebaelt Hospital, Vejle, Denmark, the primary center for the trial, is now a postdoctoral researcher at the Department of Clinical Medicine, Aarhus University, and Department of Orthopedic Surgery, Aarhus University Hospital.

“We believe that our findings are pretty robust,” Frydendal added. “I think if someone in the world conducts a trial similar to ours, they will find fairly close or consistent findings, no matter what type of exercise they choose.”

Charlotte Dahl, Lillebaelt Hospital–University Hospital of Southern Denmark, Vejle Hospital

The PROHIP Study

THR is routinely recommended for the management of severe hip osteoarthritis, but since there are no clinical trial data on the effectiveness of this procedure as compared with first-line treatment such as resistance training, the PROHIP study was conceived. 

The trial was conducted at four Danish orthopedic centers and designed as a superiority study, the hypothesis being that THR would be better at alleviating self-reported hip pain and improving hip function than resistance training. 

Of a possible 1474 individuals with a clinical suspicion of hip osteoarthritis, 791 were deemed eligible for inclusion in the trial. Inclusion criteria were being aged 50 years or older and having an indication for THR based on the presence of hip pain and clinical and radiographic findings.

However, the majority (86%) declined to enter the study, with almost half (43%) deciding to have a THR and enroll in a parallel observational cohort. This meant that only 110 (14%) individuals agreed to participate and underwent randomization, which does limit the study’s generalizability, the PROHIP investigators acknowledged. 
 

Design and Study Population

The change in Oxford Hip Score from baseline to 6 months was selected as the primary outcome measure based on the findings of a prior qualitative study. This 12-item, patient-reported outcome measure gives a score ranging from 0 to 48, with higher scores indicating less hip pain and better hip function. The estimated minimal clinically important difference is a change of 5 points. 

After a baseline assessment, 53 of 109 individuals were randomly assigned to undergo THR and 56 to participate in the resistance training program. Overall, the mean age of participants was 67.6 years, and half were women. The average duration of hip pain was a median of 1.7 years. 

The median time to receipt of the allocated treatment was 2.8 months in the THR group and 0.5 months in the resistance training group. 

Those allocated to the THR group also underwent a “fast track” program that involved patient education, pain management, and early mobilization. 

The resistance training group received 12 weeks of exercise supervised by a physiotherapist and then offered 12 weeks of additional exercise conducted on their own. The physiotherapist-supervised exercise sessions were held twice weekly and lasted for 1 hour. These started with a 10-minute warm-up on a stationary bike, followed by a standard set of resistance-based exercises that included a leg press, hip extension, hip flexion, and hip abduction. 
 

‘Reassuring’ Results

In a comment, consultant orthopedic surgeon Antony Palmer, MA, BMBCh, DPhil, said: “It’s reassuring that patients with advanced symptomatic osteoarthritis do well with hip replacements.”

THR does of course come with the potential risk for complications, but “the rate of these is what you’d expect for that procedure,” Palmer said, who works for the Nuffield Orthopaedic Centre, Oxford University Hospital NHS Foundation Trust, and is a senior clinical research fellow at Oxford University in England.

Dr. Palmer

Resistance Training Role 

A notable finding was that, at 6 months, five (9%) people assigned to the THR arm had not undergone surgery, and 12 (21%) people in the resistance training group had undergone a THR.

This could suggest two things, Palmer suggested in the interview. The first is that there could be a small proportion of people assigned to THR who may not need the operation and do well with exercise therapy. And, conversely, there may be those who would do well having the surgery without first going through the intermediate stage of physical therapy. 

It’s a suggestion that “maybe we’ve got to refine that a bit better and identify the patients that really do benefit from physiotherapy and who might not need hip replacement as a result,” Palmer said.

Or in other words, “should all patients undergo a program of physiotherapy before considering surgery?” he added.
 

Authors’ View

The PROHIP investigators conclude: “These results support current recommendations for the management of hip osteoarthritis and may be used to inform and guide shared decision making in clinical practice.”

Moreover, the results “do not oppose the use of resistance training as initial treatment,” says the authors. 

Frydendal highlighted in his interview that nearly three out of four of the patients reported not to have undertaken any type of supervised exercise before entry into the study, which is a first-line, guideline-recommended option.

“If a patient tells me, ‘I haven’t done any exercise previously,’ I’d recommend starting with completing a 6- to 12-week exercise program that is tailored to your individual needs and evaluate your symptoms afterward,” he said. 

“But we should refer the patient if our first-line treatment does not offer any improvements in the patient’s symptoms, as surgery with total hip replacement is clearly a really good treatment option,” Frydendal said.

The study was funded by the Danish Rheumatism Association, among other independent bodies. Frydendal and Palmer reported no relevant financial relationships. 
 

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

PHILADELPHIA — Low-volume bowel preparation is noninferior in adequacy to standard-volume prep in hospitalized patients undergoing colonoscopy, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.

Yale School of Medicine

“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.

Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.

“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.

In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.

After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.

In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.

Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.

Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.

In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
 

Ease of Use Is a Plus

On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”

In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).

“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.

Mayo Clinic

“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”

Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.

“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”

The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Low-volume bowel preparation is noninferior in adequacy to standard-volume prep in hospitalized patients undergoing colonoscopy, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.

Yale School of Medicine

“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.

Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.

“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.

In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.

After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.

In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.

Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.

Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.

In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
 

Ease of Use Is a Plus

On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”

In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).

“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.

Mayo Clinic

“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”

Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.

“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”

The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Low-volume bowel preparation is noninferior in adequacy to standard-volume prep in hospitalized patients undergoing colonoscopy, according to a study presented at the annual meeting of the American College of Gastroenterology (ACG).

Patients who received MoviPrep (2L of polyethylene glycol and ascorbic acid) reported higher tolerability and willingness to repeat colonoscopy preparation in the future than those taking GoLYTELY (4L of polyethylene glycol and electrolytes). In addition, the rates of electrolyte abnormalities and acute kidney injury were low and similar between the two groups.

Yale School of Medicine

“Bowel preparation remains a challenge in the inpatient setting, where 20%-50% of all colonoscopies can have inadequate bowel preparation,” said lead author Karen Xiao, MD, assistant professor in the section of digestive diseases at Yale School of Medicine, New Haven, Connecticut.

Previous studies have indicated that low-volume (2L), split-dose preparations are noninferior to high-volume (4L), split-dose regimens, and patients generally prefer low-volume options, she said. However, the current standard of care for inpatients continues to include high-volume polyethylene glycol electrocyte lavage, which may be less tolerable.

“Similar to prior studies, our study supports that MoviPrep may be a suitable alternative to traditional high-volume bowel preparation in hospitalized patients undergoing colonoscopy,” she said.

In a single-blind, multi-site, randomized controlled trial, Xiao and colleagues in the Yale–New Haven Health System randomly assigned inpatients undergoing colonoscopy to MoviPrep or GoLYTELY between January 2022 and July 2024. They excluded patients with prior small or large bowel resection, foreign body removal, or medical contraindications, such as obstruction, pregnancy, phenylketonuria, or glucose-6-phosphate dehydrogenase deficiency.

After bowel prep but before colonoscopy, patients took the Mayo Clinic Bowel Preparation survey. Colonoscopies were then recorded, and videos were scored by a single-blinded central reviewer. The primary outcome included the adequacy of bowel prep as defined by a Boston Bowel Preparation Scale score of 6 or higher, with each segment scoring 2 or higher.

In the final analysis, 202 patients received MoviPrep and 210 received GoLYTELY. In both groups, the average age was 62; about 60% were men; and 66% were White, about 22% Black, and 13%-15% Hispanic. About 65% of patients in both arms had an American Society of Anesthesiologists (ASA) score of 3, with another 20% in each group having an ASA score of 4, “reflective of a sicker inpatient population,” Xiao said.

Inpatient colonoscopy was indicated for gastrointestinal bleeding (55%), diarrhea (15%-20%), abnormal imaging (10%-13%), inflammatory bowel disease (4%), or other (35%-41%). Patients could have more than one indication for colonoscopy.

Overall, bowel preparation was scored as adequate in 111 patients with MoviPrep (55%) and 111 patients with GoLYTELY (52.9%), and was inadequate in 91 patients with MoviPrep (45%) and 99 patients with GoLYTELY (47.1%). With a rate difference of 2.1% and a P value of .007, MoviPrep was considered noninferior to GoLYTELY for adequate bowel preparation.

In terms of secondary outcomes, there wasn’t a significant difference in the length of hospital stay, with a median stay of 6 days. Similarly, there were no differences in the rates of adverse events, including acute kidney injury and electrolyte abnormalities, with rates ranging from 1% to 9%. MoviPrep patients were slightly more likely to need additional bowel prep but also had a slightly shorter time to colonoscopy.
 

Ease of Use Is a Plus

On the basis of the Mayo Clinic Bowel Preparation survey, there wasn’t a difference between the groups in how much bowel prep solution was left in the bottle. However, more than twice as many patients who took MoviPrep said the prep was “easy,” and more MoviPrep patients called it “acceptable,” whereas more GoLYTELY patients said prep was “somewhat difficult” or “very difficult.”

In addition, significantly more MoviPrep patients (49.7% vs 33.7%) said they were “mostly willing” to drink the same prep again if they needed another colonoscopy in the future, while more GoLYTELY patients said they were “somewhat willing” (44.7% vs 34.6%) or “not willing at all” (21.6% vs 15.7%).

“Bowel prep, particularly in hospitals, is important because we do it so often. When you think about what our patients in the hospital are going through, they’re very sick and often have multiple comorbidities, so how can we give them a bowel prep that is safe for them, easiest for them, easy for our nursing staff who are experiencing shortages, and as good as the traditional bowel prep,” said the session’s moderator, Amy Oxentenko, MD, AGAF, professor of medicine and gastroenterologist at Mayo Clinic, Rochester, Minnesota.

Mayo Clinic

“Here we’ve seen great data that we can provide half the volume of the prep, still get amazing results in terms of adequacy of preparation, and the patients had a better experience,” said Oxentenko, the incoming ACG president. “That’s important because they likely may need another colonoscopy in the future, and we would hate for the bowel prep in the hospital to potentially dissuade them from a future colonoscopy.”

Future studies could stratify patients on the basis of colonoscopy indication or patient history, including conditions such as chronic constipation or neurogenic bowel, where some patients may still need a high-volume prep, Oxentenko said.

“Also, in the hospital setting, we don’t always know when a patient is going to the endoscopy suite due to other patient cases that may get prolonged or pushed in,” she said. “So how do you time the second dose of the split dose in anticipation of when that patient will go to the endoscopy suite to maintain that great preparation with a smaller volume prep?”

The study was awarded the ACG Governors Award for Excellence in Clinical Research (Trainee). Xiao and Oxentenko reported no relevant disclosures.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Non-fasting breath gas patterns may help identify patients with irritable bowel syndrome (IBS) who are most likely to respond to a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet, according to a new study.

The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”

Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”

He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens. 

Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 
 

Breaths That Can Predict Response

To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale. 

Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.

Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.

Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet. 

The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day. 

Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.

The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
 

A Potential New Biomarker

Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit. 

Massachusetts General Hospital

There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.” 

Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness. 

“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role. 

Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Non-fasting breath gas patterns may help identify patients with irritable bowel syndrome (IBS) who are most likely to respond to a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet, according to a new study.

The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”

Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”

He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens. 

Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 
 

Breaths That Can Predict Response

To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale. 

Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.

Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.

Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet. 

The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day. 

Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.

The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
 

A Potential New Biomarker

Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit. 

Massachusetts General Hospital

There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.” 

Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness. 

“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role. 

Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Non-fasting breath gas patterns may help identify patients with irritable bowel syndrome (IBS) who are most likely to respond to a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet, according to a new study.

The low FODMAP diet is the most evidence-based dietary therapy for patients with IBS, but we know that “only about 50% of our patients respond to it,” said principal investigator Prashant Singh, MD, assistant professor at the University of Michigan in Ann Arbor, Michigan. “Exhaled breath gases represent bacterial fermentation of dietary carbohydrates. These measurements could provide a simple biomarker for response to low FODMAP diets.”

Even before starting the low FODMAP diet, “you could see notable differences in breath test patterns between responders and nonresponders,” he said. “We saw that low FODMAP responders had higher hydrogen (H2) and lower methane (CH4) at baseline than nonresponders and had a greater drop in hydrogen following FODMAP restriction vs nonresponders.”

He added that these results imply that responders to this diet may exhibit differences in baseline microbiota composition regarding saccharolytic capacity and/or methanogens. 

Singh presented the findings at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting. 
 

Breaths That Can Predict Response

To determine if pre-intervention non-fasting breath patterns are associated with a clinical response to low FODMAP diets, Singh and colleagues enrolled 284 self-selected participants (mean age, 45.2 years) with mild to moderate gastrointestinal (GI) symptoms. Participants used an app-connected breath analyzer to record hourly, non-fasting H2 and CH4 levels during waking hours, in addition to logging meal content and symptom severity (bloating, abdominal pain, and flatulence) on a 0-10 scale. 

Patients were directed to consume their habitual diet for 1 week, before following an app-directed low FODMAP diet for 1 week. Responders were defined as those with a ≥ 30% reduction in at least one mean symptom score. The researchers then compared average hourly H2 and CH4 levels and symptom scores at baseline between low FODMAP diet responders and nonresponders.

Of the participants, 111 were classified as responders and 173 as nonresponders. There were no significant differences between the groups in gender, age, body mass index, or FODMAP per calorie.

Following FODMAP restriction, responders had consistently lower abdominal pain throughout the day and lower bloating and flatulence predominantly in the latter part of the day. Nonresponders experienced no significant changes in key abdominal symptoms after adopting the low FODMAP diet. 

The researchers found that breath tests taken at baseline revealed predictive trends between the groups, even though average FODMAP consumption did not significantly differ between them. Baseline H2 levels were higher among responders than among nonresponders, especially in the morning and evening. However, responders had lower baseline CH4 levels throughout the day. 

Following FODMAP restrictions, responders had a significant drop in non-fasting H2 but not CH4, whereas nonresponders did not have a significant drop in either.

The study was limited by the fact that participants were not clinically diagnosed with IBS, their GI symptoms were mild overall, and no data were available on stool consistency/frequency or fecal microbiome composition for correlation with exhaled breath gas levels.
 

A Potential New Biomarker

Session co-moderator Kyle Staller, MD, MPH, director of the Gastrointestinal Motility Laboratory at Mass General and associate professor of medicine at Harvard Medical School in Boston, Massachusetts, said in an interview that if validated, these findings provide hope for better directing low FODMAP diets to those patients who may benefit. 

Massachusetts General Hospital

There are some patients who may or may not respond to a FODMAP diet, for reasons we don’t yet know, possibly related to fermentation of gas, and it’s helpful to know before starting treatment, he said. It may help us with more of “a precision medicine approach before we really torture people with diets that can be very difficult to adhere to.” 

Staller, who was not involved in the study, added that, “People tend to really focus on small intestinal bacteria overgrowth when it comes to hydrogen and methane production, but in reality, this is really a very agile day-to-day, meal-to-meal responsiveness. 

“It’s a different paradigm,” he continued. “I’d also like to see more data as to why we see the diurnal rhythm” and whether potential factors such as intestinal transit times are playing a role. 

Singh reported receiving royalties from UpToDate. Staller reported receiving research support from Ardelyx and Restasis and serving as a consultant to Anji, Ardelyx, GI Supply, Mahana, Restasis, and Sanofi. Funding associated with the study was not available at the time of publication.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — The use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) is associated with a significant decrease in the risk for early-onset colorectal cancer (EO-CRC) in patients with type 2 diabetes (T2D), according to the results of a retrospective study.

“This is the first large study to investigate the impact of GLP-1 RA use on EO-CRC risk,” principal investigator Temitope Olasehinde, MD, resident physician at the University Hospitals Cleveland Medical Center, Case Western Reserve University in Cleveland, Ohio, said in an interview.

The results indicate the GLP-1 RAs have a potentially protective role to play in combating EO-CRC, the incidence of which is notably rising in younger adults, with a corresponding increase in associated mortality.

Previous studies investigating the link between GLP-1 RAs and CRC did not capture patients aged younger than 50 years; thus, it was unknown if these results could be extrapolated to a younger age group, said Olasehinde.

The researcher presented the findings at the annual meeting of the American College of Gastroenterology.
 

Retrospective Database Analysis

Olasehinde and colleagues analyzed data from TriNetX, a large federated deidentified health research network, to identify patients (age ≤ 49 years) with diagnosed T2D subsequently prescribed antidiabetic medications who had not received a prior diagnosis of CRC. Additionally, patients were stratified on the basis of first-time GLP-1 RA use.

They identified 2,025,034 drug-naive patients with T2D; of these, 284,685 were subsequently prescribed GLP-1 RAs, and 1,740,349 remained in the non–GLP-1 RA cohort. Following propensity score matching, there were 86,186 patients in each cohort.

Patients who received GLP-1 RAs had significantly lower odds of developing EO-CRC than those who received non–GLP-1 RAs (0.6% vs 0.9%; P < .001; odds ratio [OR], 0.61; 95% CI, 0.54-068).

Furthermore, a sub-analysis revealed that patients who were obese and taking GLP-1 RAs had significantly lower odds of developing EO-CRC than patients who were obese but not taking GLP-1 RAs (0.7% vs 1.1%; P < .001; OR, 0.58; 95% CI, 0.50-067).
 

A Proposed Protective Effect

Although GLP-1 RAs are indicated for the treatment of T2D and obesity, recent evidence suggests that they may play a role in reducing the risk for CRC as well. This protective effect may be produced not only by addressing T2D and obesity — both important risk factors for CRC — but also via cellular mechanisms, Olasehinde noted.

“GLP-1 receptors are widely expressed throughout the gastrointestinal tract, with various effects on tissues in the stomach, small intestine, and colon,” she explained. Specifically, activation of these receptors in the proximal and distal colon promotes the release of “important factors that protect and facilitate healing of the intestinal epithelium” and “regulate the gut microbiome.”

This is particularly relevant in EO-CRC, she added, given its greater association with T2D and obesity, both factors that “have been shown to create dysbiosis in the gut microbiome and low-grade inflammation via release of free radicals/inflammatory cytokines.”

These results provide more evidence that EO-CRC “is clinically and molecularly distinct from late-onset colorectal cancer,” which is important for both clinicians and patients to understand, said Olasehinde.

“It is imperative that we are all aware of the specific signs and symptoms this population presents with and the implications of this diagnosis in younger age groups,” she added. “Patients should continue making informed dietary and lifestyle modifications/choices to help reduce the burden of EO-CRC.”

Hypothesis-Generating Results

Aasma Shaukat, MD, MPH, who was not affiliated with the research, called the results promising but — at this stage — primarily useful for stimulating future research. 

"We do need more studies such as this to generate hypotheses that can be studied prospectively," Shaukat, professor of medicine and population health, and director of GI Outcomes Research at NYU Langone Health in New York City, told Medscape Medical News. 

She referred to another study, published in JAMA Oncology, that also used the TriNetX research network, which showed that GLP-1 RAs were associated with reduced CRC risk in drug-naive patients with T2D. 

Shaukat also noted that the current analysis has limitations that should be considered. "The study is retrospective, and confounding is a possibility,” she said. 

“How the groups that did and did not receive GLP-1 RAs differ in other risk factors that could be the drivers of the cancers is not known. Whether cancers were detected through screening or symptoms, stage, and other features that may differ are not known. Finally, since we don’t know who did or did not have colonoscopy, undiagnosed cancers are not known," she explained. 

Shaukat, who was the lead author of the ACG 2021 Colorectal Cancer Screening Guidelines, added that the field would benefit from studies providing "biological plausibility information, such as animal studies to understand how GLP-1 RAs may modulate risk of colon cancer; other population-based cohort studies on the incidence of colon cancer among GLP-1 RA users and non-users; and prospective trials on chemoprevention." 

The study had no specific funding. Olasehinde reported no relevant financial relationships. Shaukat reported serving as a consultant for Freenome, Medtronic, and Motus GI, as well as an advisory board member for Iterative Scopes Inc.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

PHILADELPHIA — Researchers have developed an artificial intelligence (AI) tool capable of detecting and differentiating cystic and solid pancreatic lesions during endoscopic ultrasound (EUS) with high accuracy.

This was a transatlantic collaborative effort involving researchers in Portugal, Spain, the United States, and Brazil, and the AI tool “works on different platforms and different devices,” Miguel Mascarenhas, MD, PhD, with Centro Hospitalar Universitário de São João, Porto, Portugal, said in a presentation at the annual meeting of the American College of Gastroenterology.

Mascarenhas noted that pancreatic cystic lesions (PCLs) are a common incidental finding during imaging and are differentiated by whether they’re mucinous PCLs (M-PCLs) or non-mucinous PCLs (NM-PCLs). The malignancy risk is almost exclusive of PCL with a mucinous phenotype.

Pancreatic solid lesions are also prevalent, and differentiation is challenging. Pancreatic ductal adenocarcinoma (P-DAC) is the most common pancreatic solid lesion and has a poor prognosis because of late-stage disease at diagnosis. Pancreatic neuroendocrine tumors (P-NETs) are less common but have malignant potential.

EUS is the “gold standard” for pancreatic lesion evaluation, but its diagnostic accuracy is suboptimal, particularly for lesions < 10 mm, Mascarenhas noted.

With an eye toward improving diagnostic accuracy, he and colleagues developed a convolutional neural network for detecting and differentiating cystic (M-PCL and NM-PCL) and solid (P-DAC and P-NET) pancreatic lesions.

They leveraged data from 378 EUS exams with 126,000 still images — 19,528 M-PCL, 8175 NM-PCL, 64,286 P-DAC, 29,153 P-NET, and 4858 normal pancreas images.

The AI tool demonstrated 99.1% accuracy for identifying normal pancreatic tissue, and it showed 99% and 99.8% accuracy for M-PCL and NM-PCL, respectively.

For pancreatic solid lesions, P-DAC and P-NET were distinguished with 94% accuracy, with 98.7% and 83.6% sensitivity for P-DAC and P-NET, respectively.
 

Real-Time Validation Next

“AI is delivering promising results throughout medicine, but particularly in gastroenterology, which is one of the most fertile areas of AI research. This comes mostly from the deployment of deep-learning models, most of them convolutional neural networks, which are highly efficient for image analysis,” Mascarenhas told attendees.

This is the “first worldwide convolutional neural network” capable of detecting and differentiating both cystic and solid pancreatic lesions. The use of a large dataset from four centers in two continents helps minimize the impact of demographic bias, Mascarenhas added.

The study is based on still images, not full videos, he noted. As a next step, the team is conducting a multicenter study focused on real-time clinical validation of the model during EUS procedures.

“AI has the potential to improve the diagnostic accuracy of endoscopic ultrasound. We’re just on the tip of the iceberg. There is enormous potential to harness AI, and we welcome all the groups that might want to join our research,” Mascarenhas said.

Brennan Spiegel, MD, MSHS, AGAF, director of Health Services Research at Cedars-Sinai Medical Center, Los Angeles, who wasn’t involved in the study, is optimistic about emerging applications for AI.

“AI holds incredible promise in gastroenterology, especially for diagnosing complex pancreatic lesions where early, accurate differentiation can be lifesaving,” Spiegel said in an interview.

“This study’s high accuracy across diverse datasets is encouraging; however, as a retrospective analysis, it leaves the real-time clinical impact still to be proven. Prospective studies will be essential to confirm AI’s role in enhancing our diagnostic capabilities,” Spiegel cautioned.

“More generally, AI is rapidly transforming gastroenterology by enhancing our ability to detect, differentiate, and monitor conditions with unprecedented precision. From improving early cancer detection to guiding complex diagnostic procedures, AI stands to become an invaluable tool that complements clinical expertise. As we refine these technologies, the potential for AI to elevate both diagnostic accuracy and patient outcomes in GI is truly remarkable,” Spiegel said.

The study had no specific funding. Mascarenhas and Spiegel have declared no conflicts of interest.

A version of this article appeared on Medscape.com.

I was invited to a cardiology conference to talk about sleep, specifically the benefits of napping for health and cognition. After the talk, along with the usual questions related to my research, the cardiac surgeons in the room shifted the conversation to better resemble a group therapy session, sharing their harrowing personal tales of coping with sleep loss on the job. The most dramatic story involved a resident in a military hospital who, unable to avoid the effects of her mounting sleep loss, did a face plant into the open chest of the patient on the surgery table.

Sleep is inexorable.

Yet humans generally do not get sufficient sleep, and a growing body of research indicates that this deficit is taking a toll on day-to-day functioning, as well as long-term health outcomes. Epidemiology studies have associated insufficient sleep with increased disease risk, including cardiovascular and metabolic disease, diabetes, cancer, Alzheimer’s disease and related dementias, as well as early mortality. Laboratory studies that experimentally restrict sleep show deficits across many cognitive domains, including executive functions, long-term memory, as well as emotional processing and regulation. Insufficient sleep in adolescents can longitudinally predict depression, thought problems, and lower crystallized intelligence, as well as structural brain properties. In older adults, it can predict the onset of chronic disease, including Alzheimer’s disease. Repeated nights of insufficient sleep (eg, three to four nights of four to six hours of sleep) have been shown to dysregulate hormone release, elevate body temperature and heart rate, stimulate appetite, and create an imbalance between the two branches of the autonomic nervous system by prolonging sympathetic activity and reducing parasympathetic restorative activity.

Given this ever-increasing list of ill effects of poor sleep, the quest for an effective, inexpensive, and manageable intervention for sleep loss often leads to the question: What about naps? A nap is typically defined as a period of sleep between five minutes to three hours, although naps can occur at any hour, they are usually daytime sleep behaviors. Between 40% and 60% of adults nap regularly, at least once a week, and, excluding novelty nap boutiques, they are free of charge and require little management or oversight. Yet, for all their apparent positive aspects, the jury is still out on whether naps should be recommended as a sleep loss countermeasure due to the lack of agreement across studies as to their effects on health.

Naps are studied in primarily two scientific contexts: laboratory experimental studies and epidemiological studies. Laboratory experimental studies measure the effect of short bouts of sleep as a fatigue countermeasure or cognitive enhancer under total sleep deprivation, sleep restriction (four to six hours of nighttime sleep), or well-rested conditions. These experiments are usually conducted in small (20 to 30 participants) convenience samples of young adults without medical and mental health problems. Performance on computer-based cognitive tasks is tested before and after naps of varying durations. By varying nap durations, researchers can test the impact of specific sleep stages on performance improvement. For example, in well-rested, intermediate chronotype individuals, a 30-minute nap between 13:00 and 15:00 will contain mostly stage 2 sleep, whereas a nap of up to 60 minutes will include slow wave sleep, and a 90-minute nap will end on a bout of rapid eye movement sleep. Studies that vary nap duration and therefore sleep quality have demonstrated an important principle of sleep’s effect on the brain and cognitive processing, namely that each sleep stage uniquely contributes to different aspects of cognitive and emotional processing. And that when naps are inserted into a person’s day, even in well-rested conditions, they tend to perform better after the nap than if they had stayed awake. Napping leads to greater vigilance, attention, memory, motor performance, and creativity, among others, compared with equivalent wake periods.^1,2 Compared with the common fatigue countermeasure—caffeine—naps enhance explicit memory performance to a greater extent.

References

1. Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci. 2003 Jul;6(7):697-8. doi: 10.1038/nn1078. PMID: 12819785.

2. Jones BJ, Spencer RMC. Role of Napping for Learning across the Lifespan. Curr Sleep Med Rep. 2020 Dec;6(4):290-297. Doi: 10.1007/s40675-020-00193-9. Epub 2020 Nov 12. PMID: 33816064; PMCID: PMC8011550.

3. Dunietz GL, Jansen EC, Hershner S, O’Brien LM, Peterson KE, Baylin A. Parallel Assessment Challenges in Nutritional and Sleep Epidemiology. Am J Epidemiol. 2021 Jun 1;190(6):954-961. doi: 10.1093/aje/kwaa230. PMID: 33089309; PMCID: PMC8168107.

4. Stang A. Daytime napping and health consequences: much epidemiologic work to do. Sleep Med. 2015 Jul;16(7):809-10. doi: 10.1016/j.sleep.2015.02.522. Epub 2015 Feb 14. PMID: 25772544.

5. Li, P., Gao, L., Yu, L., Zheng, X., Ulsa, M. C., Yang, H.-W., Gaba, A., Yaffe, K., Bennett, D. A., Buchman, A. S., Hu, K., & Leng, Y. (2022). Daytime napping and Alzheimer’s dementia: A potential bidirectional relationship. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association. https://doi.org/10.1002/alz.12636

6. Stang A, Dragano N., Moebus S, et al. Midday naps and the risk of coronary artery disease: results of the Heinz Nixdorf Recall Study Sleep, 35 (12) (2012), pp. 1705-1712

7. Wang K, Hu L, Wang L, Shu HN, Wang YT, Yuan Y, Cheng HP, Zhang YQ. Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China. Biomed Environ Sci. 2023 Aug 20;36(8):702-714. doi: 10.3967/bes2023.073. PMID: 37711082.

8. Naska A, Oikonomou E, Trichopoulou A, Psaltopoulou T, Trichopoulos D. Siesta in healthy adults and coronary mortality in the general population. Arch Intern Med. 2007 Feb 12;167(3):296-301. Doi: 10.1001/archinte.167.3.296. PMID: 17296887.

9. Paz V, Dashti HS, Garfield V. Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank. Sleep Health. 2023 Oct;9(5):786-793. Doi: 10.1016/j.sleh.2023.05.002. Epub 2023 Jun 20. PMID: 37344293.

10. Mednick SC. Is napping in older adults problematic or productive? The answer may lie in the reason they nap. Sleep. 2024 May 10;47(5):zsae056. doi: 10.1093/sleep/zsae056. PMID: 38421680; PMCID: PMC11082470.

11. Duggan KA, McDevitt EA, Whitehurst LN, Mednick SC. To Nap, Perchance to DREAM: A Factor Analysis of College Students’ Self-Reported Reasons for Napping. Behav Sleep Med. 2018 Mar-Apr;16(2):135-153. doi: 10.1080/15402002.2016.1178115. Epub 2016 Jun 27. PMID: 27347727; PMCID: PMC5374038.

I was invited to a cardiology conference to talk about sleep, specifically the benefits of napping for health and cognition. After the talk, along with the usual questions related to my research, the cardiac surgeons in the room shifted the conversation to better resemble a group therapy session, sharing their harrowing personal tales of coping with sleep loss on the job. The most dramatic story involved a resident in a military hospital who, unable to avoid the effects of her mounting sleep loss, did a face plant into the open chest of the patient on the surgery table.

Sleep is inexorable.

Yet humans generally do not get sufficient sleep, and a growing body of research indicates that this deficit is taking a toll on day-to-day functioning, as well as long-term health outcomes. Epidemiology studies have associated insufficient sleep with increased disease risk, including cardiovascular and metabolic disease, diabetes, cancer, Alzheimer’s disease and related dementias, as well as early mortality. Laboratory studies that experimentally restrict sleep show deficits across many cognitive domains, including executive functions, long-term memory, as well as emotional processing and regulation. Insufficient sleep in adolescents can longitudinally predict depression, thought problems, and lower crystallized intelligence, as well as structural brain properties. In older adults, it can predict the onset of chronic disease, including Alzheimer’s disease. Repeated nights of insufficient sleep (eg, three to four nights of four to six hours of sleep) have been shown to dysregulate hormone release, elevate body temperature and heart rate, stimulate appetite, and create an imbalance between the two branches of the autonomic nervous system by prolonging sympathetic activity and reducing parasympathetic restorative activity.

Given this ever-increasing list of ill effects of poor sleep, the quest for an effective, inexpensive, and manageable intervention for sleep loss often leads to the question: What about naps? A nap is typically defined as a period of sleep between five minutes to three hours, although naps can occur at any hour, they are usually daytime sleep behaviors. Between 40% and 60% of adults nap regularly, at least once a week, and, excluding novelty nap boutiques, they are free of charge and require little management or oversight. Yet, for all their apparent positive aspects, the jury is still out on whether naps should be recommended as a sleep loss countermeasure due to the lack of agreement across studies as to their effects on health.

Naps are studied in primarily two scientific contexts: laboratory experimental studies and epidemiological studies. Laboratory experimental studies measure the effect of short bouts of sleep as a fatigue countermeasure or cognitive enhancer under total sleep deprivation, sleep restriction (four to six hours of nighttime sleep), or well-rested conditions. These experiments are usually conducted in small (20 to 30 participants) convenience samples of young adults without medical and mental health problems. Performance on computer-based cognitive tasks is tested before and after naps of varying durations. By varying nap durations, researchers can test the impact of specific sleep stages on performance improvement. For example, in well-rested, intermediate chronotype individuals, a 30-minute nap between 13:00 and 15:00 will contain mostly stage 2 sleep, whereas a nap of up to 60 minutes will include slow wave sleep, and a 90-minute nap will end on a bout of rapid eye movement sleep. Studies that vary nap duration and therefore sleep quality have demonstrated an important principle of sleep’s effect on the brain and cognitive processing, namely that each sleep stage uniquely contributes to different aspects of cognitive and emotional processing. And that when naps are inserted into a person’s day, even in well-rested conditions, they tend to perform better after the nap than if they had stayed awake. Napping leads to greater vigilance, attention, memory, motor performance, and creativity, among others, compared with equivalent wake periods.^1,2 Compared with the common fatigue countermeasure—caffeine—naps enhance explicit memory performance to a greater extent.

References

1. Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci. 2003 Jul;6(7):697-8. doi: 10.1038/nn1078. PMID: 12819785.

2. Jones BJ, Spencer RMC. Role of Napping for Learning across the Lifespan. Curr Sleep Med Rep. 2020 Dec;6(4):290-297. Doi: 10.1007/s40675-020-00193-9. Epub 2020 Nov 12. PMID: 33816064; PMCID: PMC8011550.

3. Dunietz GL, Jansen EC, Hershner S, O’Brien LM, Peterson KE, Baylin A. Parallel Assessment Challenges in Nutritional and Sleep Epidemiology. Am J Epidemiol. 2021 Jun 1;190(6):954-961. doi: 10.1093/aje/kwaa230. PMID: 33089309; PMCID: PMC8168107.

4. Stang A. Daytime napping and health consequences: much epidemiologic work to do. Sleep Med. 2015 Jul;16(7):809-10. doi: 10.1016/j.sleep.2015.02.522. Epub 2015 Feb 14. PMID: 25772544.

5. Li, P., Gao, L., Yu, L., Zheng, X., Ulsa, M. C., Yang, H.-W., Gaba, A., Yaffe, K., Bennett, D. A., Buchman, A. S., Hu, K., & Leng, Y. (2022). Daytime napping and Alzheimer’s dementia: A potential bidirectional relationship. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association. https://doi.org/10.1002/alz.12636

6. Stang A, Dragano N., Moebus S, et al. Midday naps and the risk of coronary artery disease: results of the Heinz Nixdorf Recall Study Sleep, 35 (12) (2012), pp. 1705-1712

7. Wang K, Hu L, Wang L, Shu HN, Wang YT, Yuan Y, Cheng HP, Zhang YQ. Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China. Biomed Environ Sci. 2023 Aug 20;36(8):702-714. doi: 10.3967/bes2023.073. PMID: 37711082.

8. Naska A, Oikonomou E, Trichopoulou A, Psaltopoulou T, Trichopoulos D. Siesta in healthy adults and coronary mortality in the general population. Arch Intern Med. 2007 Feb 12;167(3):296-301. Doi: 10.1001/archinte.167.3.296. PMID: 17296887.

9. Paz V, Dashti HS, Garfield V. Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank. Sleep Health. 2023 Oct;9(5):786-793. Doi: 10.1016/j.sleh.2023.05.002. Epub 2023 Jun 20. PMID: 37344293.

10. Mednick SC. Is napping in older adults problematic or productive? The answer may lie in the reason they nap. Sleep. 2024 May 10;47(5):zsae056. doi: 10.1093/sleep/zsae056. PMID: 38421680; PMCID: PMC11082470.

11. Duggan KA, McDevitt EA, Whitehurst LN, Mednick SC. To Nap, Perchance to DREAM: A Factor Analysis of College Students’ Self-Reported Reasons for Napping. Behav Sleep Med. 2018 Mar-Apr;16(2):135-153. doi: 10.1080/15402002.2016.1178115. Epub 2016 Jun 27. PMID: 27347727; PMCID: PMC5374038.

I was invited to a cardiology conference to talk about sleep, specifically the benefits of napping for health and cognition. After the talk, along with the usual questions related to my research, the cardiac surgeons in the room shifted the conversation to better resemble a group therapy session, sharing their harrowing personal tales of coping with sleep loss on the job. The most dramatic story involved a resident in a military hospital who, unable to avoid the effects of her mounting sleep loss, did a face plant into the open chest of the patient on the surgery table.

Sleep is inexorable.

Yet humans generally do not get sufficient sleep, and a growing body of research indicates that this deficit is taking a toll on day-to-day functioning, as well as long-term health outcomes. Epidemiology studies have associated insufficient sleep with increased disease risk, including cardiovascular and metabolic disease, diabetes, cancer, Alzheimer’s disease and related dementias, as well as early mortality. Laboratory studies that experimentally restrict sleep show deficits across many cognitive domains, including executive functions, long-term memory, as well as emotional processing and regulation. Insufficient sleep in adolescents can longitudinally predict depression, thought problems, and lower crystallized intelligence, as well as structural brain properties. In older adults, it can predict the onset of chronic disease, including Alzheimer’s disease. Repeated nights of insufficient sleep (eg, three to four nights of four to six hours of sleep) have been shown to dysregulate hormone release, elevate body temperature and heart rate, stimulate appetite, and create an imbalance between the two branches of the autonomic nervous system by prolonging sympathetic activity and reducing parasympathetic restorative activity.

Given this ever-increasing list of ill effects of poor sleep, the quest for an effective, inexpensive, and manageable intervention for sleep loss often leads to the question: What about naps? A nap is typically defined as a period of sleep between five minutes to three hours, although naps can occur at any hour, they are usually daytime sleep behaviors. Between 40% and 60% of adults nap regularly, at least once a week, and, excluding novelty nap boutiques, they are free of charge and require little management or oversight. Yet, for all their apparent positive aspects, the jury is still out on whether naps should be recommended as a sleep loss countermeasure due to the lack of agreement across studies as to their effects on health.

Naps are studied in primarily two scientific contexts: laboratory experimental studies and epidemiological studies. Laboratory experimental studies measure the effect of short bouts of sleep as a fatigue countermeasure or cognitive enhancer under total sleep deprivation, sleep restriction (four to six hours of nighttime sleep), or well-rested conditions. These experiments are usually conducted in small (20 to 30 participants) convenience samples of young adults without medical and mental health problems. Performance on computer-based cognitive tasks is tested before and after naps of varying durations. By varying nap durations, researchers can test the impact of specific sleep stages on performance improvement. For example, in well-rested, intermediate chronotype individuals, a 30-minute nap between 13:00 and 15:00 will contain mostly stage 2 sleep, whereas a nap of up to 60 minutes will include slow wave sleep, and a 90-minute nap will end on a bout of rapid eye movement sleep. Studies that vary nap duration and therefore sleep quality have demonstrated an important principle of sleep’s effect on the brain and cognitive processing, namely that each sleep stage uniquely contributes to different aspects of cognitive and emotional processing. And that when naps are inserted into a person’s day, even in well-rested conditions, they tend to perform better after the nap than if they had stayed awake. Napping leads to greater vigilance, attention, memory, motor performance, and creativity, among others, compared with equivalent wake periods.^1,2 Compared with the common fatigue countermeasure—caffeine—naps enhance explicit memory performance to a greater extent.

References

1. Mednick S, Nakayama K, Stickgold R. Sleep-dependent learning: a nap is as good as a night. Nat Neurosci. 2003 Jul;6(7):697-8. doi: 10.1038/nn1078. PMID: 12819785.

2. Jones BJ, Spencer RMC. Role of Napping for Learning across the Lifespan. Curr Sleep Med Rep. 2020 Dec;6(4):290-297. Doi: 10.1007/s40675-020-00193-9. Epub 2020 Nov 12. PMID: 33816064; PMCID: PMC8011550.

3. Dunietz GL, Jansen EC, Hershner S, O’Brien LM, Peterson KE, Baylin A. Parallel Assessment Challenges in Nutritional and Sleep Epidemiology. Am J Epidemiol. 2021 Jun 1;190(6):954-961. doi: 10.1093/aje/kwaa230. PMID: 33089309; PMCID: PMC8168107.

4. Stang A. Daytime napping and health consequences: much epidemiologic work to do. Sleep Med. 2015 Jul;16(7):809-10. doi: 10.1016/j.sleep.2015.02.522. Epub 2015 Feb 14. PMID: 25772544.

5. Li, P., Gao, L., Yu, L., Zheng, X., Ulsa, M. C., Yang, H.-W., Gaba, A., Yaffe, K., Bennett, D. A., Buchman, A. S., Hu, K., & Leng, Y. (2022). Daytime napping and Alzheimer’s dementia: A potential bidirectional relationship. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association. https://doi.org/10.1002/alz.12636

6. Stang A, Dragano N., Moebus S, et al. Midday naps and the risk of coronary artery disease: results of the Heinz Nixdorf Recall Study Sleep, 35 (12) (2012), pp. 1705-1712

7. Wang K, Hu L, Wang L, Shu HN, Wang YT, Yuan Y, Cheng HP, Zhang YQ. Midday Napping, Nighttime Sleep, and Mortality: Prospective Cohort Evidence in China. Biomed Environ Sci. 2023 Aug 20;36(8):702-714. doi: 10.3967/bes2023.073. PMID: 37711082.

8. Naska A, Oikonomou E, Trichopoulou A, Psaltopoulou T, Trichopoulos D. Siesta in healthy adults and coronary mortality in the general population. Arch Intern Med. 2007 Feb 12;167(3):296-301. Doi: 10.1001/archinte.167.3.296. PMID: 17296887.

9. Paz V, Dashti HS, Garfield V. Is there an association between daytime napping, cognitive function, and brain volume? A Mendelian randomization study in the UK Biobank. Sleep Health. 2023 Oct;9(5):786-793. Doi: 10.1016/j.sleh.2023.05.002. Epub 2023 Jun 20. PMID: 37344293.

10. Mednick SC. Is napping in older adults problematic or productive? The answer may lie in the reason they nap. Sleep. 2024 May 10;47(5):zsae056. doi: 10.1093/sleep/zsae056. PMID: 38421680; PMCID: PMC11082470.

11. Duggan KA, McDevitt EA, Whitehurst LN, Mednick SC. To Nap, Perchance to DREAM: A Factor Analysis of College Students’ Self-Reported Reasons for Napping. Behav Sleep Med. 2018 Mar-Apr;16(2):135-153. doi: 10.1080/15402002.2016.1178115. Epub 2016 Jun 27. PMID: 27347727; PMCID: PMC5374038.