Sleep Medicine

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Richard* was a master-of-the-universe type. He went to Wharton, ran a large hedge fund, and lived in Greenwich, Connecticut. His three children attended Ivy League schools. He played golf on the weekends and ate three healthy meals per day. There was just one issue: He had gained 90 pounds since the 1990s from consuming six to seven alcoholic beverages per day. He already had one DUI under his belt, and his marriage was on shaky ground. He had tried to address his alcohol abuse disorder on multiple occasions: He went to a yearlong class on alcoholism, saw a psychologist for cognitive-behavioral therapy, and joined Alcoholics Anonymous, all to no avail. 

When I met him in December 2023, he had hit rock bottom and was willing to try anything.

At our first visit, I prescribed him weekly tirzepatide (Zepbound) off label, along with a small dose of naltrexone. 

Richard shared some feedback after his first 2 weeks:

The naltrexone works great and is strong ... small dose for me effective ... I haven’t wanted to drink and when I do I can’t finish a glass over 2 hours … went from 25 drinks a week to about 4 … don’t notice other side effects … sleeping better too.

And after 6 weeks:

Some more feedback … on week 6-7 and all going well ... drinking very little alcohol and still on half tab of naltrexone ... that works well and have no side effects ... the Zepbound works well too. I do get hungry a few days after the shot but still don’t crave sugar or bad snacks … weight down 21 pounds since started … 292 to 271.

And finally, after 8 weeks:

Looking at my last text to you I see the progress … been incredible ... now down 35 pounds and at 257 … continue to feel excellent with plenty of energy … want to exercise more ... and no temptation to eat or drink unhealthy stuff ... I’m very happy this has surpassed my expectations on how fast it’s worked and I don’t feel any side effects. Marriage has never been better … all thanks to you. 

Tirzepatide contains two hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), that are naturally produced by our bodies after meals. Scientists recently learned that the GLP-1 system contributes to the feedback loop of addictive behaviors. Increasing synthetic GLP-1, through medications like tirzepatide, appears to minimize addictive behaviors by limiting their ability to upregulate the brain’s production of dopamine. 

Dopamine is a neurotransmitter produced in the brain’s reward center, which regulates how people experience pleasure and control impulses. Dopamine reinforces the pleasure experienced by certain behaviors like drinking, smoking, and eating sweets. These new medications reduce the amount of dopamine released after these activities and thereby lower the motivation to repeat these behaviors. 

Contrary to some reports in the news, the vast majority of my male patients using these medications for alcohol abuse disorder experience concurrent increases in testosterone, for two reasons: (1) testosterone increases as body mass index decreases and (2) chronic alcohol use can damage the cells in the testicles that produce testosterone and also decrease the brain’s ability to stimulate the testicles to produce testosterone. 

At his most recent checkup last month, Richard’s testosterone had risen from borderline to robust levels, his libido and sleep had improved, and he reported never having felt so healthy or confident. Fingers crossed that the US Food and Drug Administration won’t wait too long before approving this class of medications for more than just diabetes, heart disease, and obesity. 

*Patient’s name has been changed.
 

Dr. Messer is clinical assistant professor, Icahn School of Medicine at Mount Sinai, New York, and associate professor, Zucker School of Medicine at Hofstra University, Hempstead, New York. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Non-respiratory symptoms including poor sleep, fatigue, pain, anxiety, and depressive symptoms were prevalent among adults with cystic fibrosis (AwCF) and persisted after 1 year of follow-up, based on data from more than 200 individuals in a study presented at the American Thoracic Society (ATS) 2024 International Conference.

“People with cystic fibrosis have qualitatively reported burden from extrapulmonary symptoms that were not being addressed by their health care providers; this is the first study to examine these symptoms concurrently in a large sample over time,” said lead author Kristin A. Riekert, PhD, of Johns Hopkins University, Baltimore, in an interview.

Previous cross-sectional studies have shown a high prevalence of poor sleep quality, fatigue, pain, depression, and anxiety among AwCF, but longitudinal data showing the persistence of symptoms are lacking, Dr. Riekert and colleagues noted in their abstract.
 

Sleep Quality, Anxiety, and Other Assessments

The researchers recruited a total of 236 AwCF aged 18 years and older from two cystic fibrosis (CF) centers between April 2021 and August 2022. They examined the prevalence of poor sleep quality, fatigue pain, depression, and anxiety in AwCF on the basis of five assessments: At baseline and at 3, 6, 9, and 12 months.

Participants were assessed via an online survey using the Fatigue Severity Scale (cutoff, > 4), Pittsburgh Sleep Quality Index (cutoff, > 5), Patient Health Questionnaire (cutoff, > 9), Generalized Anxiety Disorder (cutoff, > 9), and PROMIS Pain Intensity (cutoff, > 50 T score). Chronic symptoms were defined as positive scores on four or more assessments for individuals who completed four or five time-point assessments. The mean age of the participants was 37 years, 52% were women, 95% were non-Hispanic White, and 86% had been prescribed CF modulator therapy.

At 12 months, 62% of participants reported poor sleep, and 34% reported fatigue. In addition, 17% reported depressive symptoms, 14% reported anxiety symptoms, and 7% reported pain at 12 months.

Overall, 49% of participants met the criteria for chronic poor sleep quality, and 29% met the criteria for chronic fatigue, with positive assessments at four or more time points over the course of a year. In addition, 40%, 30%, and 18% of participants reported taking medication in the past 7 days for pain, mental health, and sleep, respectively.

The findings suggest that patients with CF might benefit from routine assessments of non-pulmonary symptoms in clinical care and from access to health care providers, including mental health professionals, to address non-pulmonary concerns, the researchers wrote in their abstract.

“We delayed starting the study until elexacaftor/tezacaftor/ivacaftor (ETI) was FDA-approved because there was an assumption that people with CF would have less fatigue because of respiratory improvements from ETI,” Dr. Riekert told this news organization. “Instead, the prevalence of fatigue and poor sleep quality was higher and more chronic than we had anticipated,” she noted.

However, “we were pleasantly surprised that depression and anxiety, while still prevalent, were less prevalent and chronic than previously reported,” Dr. Riekert said in an interview. “We attribute this to the CF Foundation’s mental health initiative that has increased the frequency of annual screening for depression and anxiety and provided resources to help people with cystic fibrosis obtain mental health services,” she said.

The study findings suggest that clinicians should assess people with CF for chronic fatigue and poor sleep along with depression and anxiety and provide treatment or referral, Dr. Riekert said. “For example, cognitive behavioral therapy can effectively treat all the symptoms that were measured in our study,” she noted.

Limitations of the study include the lack of data on how the non-respiratory symptoms interact with respiratory symptoms or pulmonary exacerbations, said Dr. Riekert. “While we assessed these symptoms five times, it was for a year; longer-term follow-up seems merited given our findings,” she said. In addition, “we need to study approaches to make cognitive behavioral therapy and other therapy more accessible for people with cystic fibrosis,” Dr. Riekert said.
 

Targeting Non-Pulmonary Dimensions of CF Care

The current study highlights an aspect of quality of life that is often forgotten when managing adults with CF and may affect their well-being despite effective therapy to improve function and prolong life, said Wissam Chatila, MD, professor of thoracic medicine and surgery at the Lewis Katz School of Medicine at Temple University, Philadelphia, in an interview.

The high incidence of poor sleep, fatigue, depression, and anxiety seen in the current study was “somewhat surprising,” Dr. Chatila said. Also somewhat surprising was the chronicity of the symptoms considering the cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies (designed to correct the malfunctioning protein made by the CFTR gene) that have changed the face of CF, he noted.

However, recent growth in the number of adult patients with CF (more than 50% in certain countries) has led to a change in pathologies that physicians have to manage, and the current study addresses some of the emerging pathologies, said Dr. Chatila.

“Beyond demonstrating survival data from registries and other epidemiologic studies, this study sheds light on the need to address patient-reported outcomes that may or may not be directly related to the pulmonary and GI effects of the CFTR modulators,” he said. “Recognizing the extent of the dysfunction that many CF patients continue to suffer from will eventually lead to identifying factors that contribute to poor outcomes and the mechanisms involved,” he added.

Overall, the current study illustrates the potential benefits of offering personalized medicine to adults with CF that improves not only their physical function but also their mental health, Dr. Chatila said.

The study was funded by the Cystic Fibrosis Foundation. Dr. Riekert had no financial conflicts to disclose. Dr. Chatila had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

NASHVILLE, TENNESSEE — Fatigue and sleep problems are common among patients with multiple sclerosis (MS), but there are ways to help them manage these difficulties through personalized care.

Fatigue related to MS is complex, but it often follows a pattern. “Oftentimes when I meet with patients for the first time, they’re not always sure [what their own pattern is]. They know that the fatigue is present, and it’s limiting their activities. It’s important for us to break down and see that pattern for [the patient] specifically, and what are some ways that we can intervene to perhaps make that pattern something that improves quality of life and day-to-day living,” said Grace Tworek, PsyD, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers (CMSC).

A cycle may start on a day that a patient has lots of energy. They are ambitious that day and get a lot done on their “to do” list while they have the energy. Unfortunately, they commonly overdo it, leading to fatigue the next day. Over ensuing days, the patient might feel unable to engage in everyday tasks and begin to feel they are falling behind. This in turn can affect mood, resulting in increased symptoms of depression and anxiety. That leads to days of inactivity and rest, which leads to recovery. Then comes a day with better mood and increased energy, where the cycle can begin again.

It’s an addressable problem. “What we really want to do is break this cycle, get out of those peaks and valleys of high energy days and very low energy days to try to create more sustainable patterns” said Dr. Tworek, who is a staff health psychologist at Cleveland Clinic’s Mellen Center for Multiple Sclerosis, Cleveland, Ohio.
 

Fatigue

When addressing fatigue in MS patients, Dr. Tworek and her colleagues begin with a fatigue diary that includes typical activities engaged in throughout the day. It also distinguishes between activities the patient feels are important and activities that give them satisfaction.

“If we can find ways to include these [satisfying] activities, and not focus only on those important activities. This is where that quality of life really comes into play. But I always say to folks, we are not striving for perfection at first. I want you to write down what’s actually happening so we can use this data to later inform how we are going to make changes,” said Dr. Tworek.

It’s also important to encourage patients to seek help. Activities that are neither important nor satisfying may not need doing at all, and they encourage patients to seek help in other tasks. As for tasks that are important in their day-to-day lives, “How can we break those down? We break those down by pacing activities,” said Dr. Tworek.

A simple way to pace yourself is to use “The rule of two.” It asks: How long can I do a task before I experience a two-point increase on a 1-10 fatigue scale. “At that time, is when we want to start inserting breaks. We want to find activities we can do that will reduce [fatigue] or get us back to baseline. Or if that’s not realistic, keep us where we are at rather than increasing fatigue,” said Dr. Tworek.

Another way to think about it is spoon theory, sometimes referred to as coin theory. The idea is that you wake up each morning with ten spoons. Each task on a given day will cost a certain number of spoons. “You might start your day, you go downstairs, you have breakfast, and you’re already down to seven points, the next day, you might still be at 10. So it’s really about monitoring where you’re at in terms of how many coins or spoons you’re spending so that we can then reflect on how many coins or spoons do I have left?” said Dr. Tworek.

The strategy can aid communication with partners or family members who may have difficulty understanding MS fatigue. “Sometimes putting a number to it can really open up the doors to having these difficult conversations with friends and family,” said Dr. Tworek.
 

Sleep

Fatigue and sleep are naturally intertwined, and sleep problems are also common in MS, with 30%-56% reporting problems, depending on the estimate.

One concept to think about is sleep drive. “From the moment we wake up, we are building sleep pressure, just like from the moment you stop eating, your body starts building pressure to eat again,” said Dr. Tworek.

Naps can interfere with that drive, much like a snack can rob you of a meal-time appetite. “A nap is going to curb that appetite for sleep, making it more difficult potentially to fall asleep,” said Dr. Tworek. If a nap is absolutely necessary, it’s better to do it earlier in the day to allow time to build sleep pressure again.

As with fatigue, Dr. Tworek has patients fill out a sleep diary that documents difficulty falling or staying asleep, timing and length of awakenings, quality of sleep, length and timing of any naps, and other factors. It sometimes reveals patterns, like difficulty falling asleep on specific days of the week. Such rhythms may be attributable to regular stressors, like anticipating some event the next morning. Then it might be possible to tie in other techniques like stress management to reduce accompanying anxiety.

Sleep hygiene is an important factor, employing strategies like staying off screens or social media while in bed. “About 1 hour before bedtime, we want to try to create some relaxation time,” said Dr. Tworek.

Her clinic also emphasizes consistent wake time. “If we are waking every day in about the same half hour period, we are able to build that sleep pressure consistently. [Then] your body is going to let you know when it is time for bed. You’re going to feel sleepiness,” said Dr. Tworek.

Dr. Tworek did not report any disclosures or conflicts of interest.

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Seltorexant, an investigational drug being developed by Johnson & Johnson, met all primary and secondary endpoints in a phase 3 trial of patients with major depressive disorder (MDD) with insomnia symptoms, the company has announced.

Seltorexant is an investigational potential first-in-class selective antagonist of the human orexin 2 receptor being studied for the adjunctive treatment of MDD with insomnia symptoms. Its selective mechanism of action means it has the potential to improve both mood and sleep symptoms associated with depression.

The phase 3 MDD3001 study was a multicenter, randomized, double-blind trial comparing the efficacy and safety of 20-mg oral seltorexant once daily with placebo, added to background selective serotonin reuptake inhibitor/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) therapy, for improving depressive symptoms in adult and elderly patients with MDD with insomnia symptoms.

In the study, seltorexant led to “statistically significant and clinically meaningful” improvement in depressive symptoms based on the Montgomery-Asberg Depression Rating Scale total score, as well as improved sleep disturbance outcomes, in patients with moderate to severe depression and severe sleep disturbance who had a prior inadequate response to SSRI/SNRI antidepressants alone, the company announced in a statement.

Consistent with previous trials of seltorexant, the drug was safe and well-tolerated, with similar rates of common adverse events seen in both treatment groups.

“Depression is a leading cause of disability worldwide and shares a strong link with sleep disturbances. In MDD, insomnia symptoms exacerbate the risk of depressive relapse, increase healthcare costs, and impact quality of life, and it often goes undertreated despite being one of the most common residual symptoms,” Andrew Krystal, MD, professor of psychiatry, University of California, San Francisco Weill Institute for Neurosciences, said in the statement.

“Seltorexant has the potential to fill a significant unmet need for new therapies to treat patients experiencing depression and insomnia and, most importantly, to improve outcomes and quality of life for these patients,” Dr. Krystal added.

The topline results are being presented at the American Society of Clinical Psychopharmacology (ASCP) 2024 Annual Meeting in Miami, Florida.

The positive phase 3 data follow earlier promising data reported in 2022, as reported by this news organization.

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

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

AIRWAYS DISORDERS NETWORK

Pediatric Chest Medicine Section

Children with severe lower respiratory tract infections (LRTIs) within the first 2 years of life had a 2.06-fold increased risk of developing pediatric OSA by age 5, according to a study comparing patients hospitalized with LRTI to controls without severe LRTI.¹ Prior studies linked LRTI and OSA, but the impact of LRTI severity was unknown.^2,3,4Using a case-control design, researchers analyzed data from 2,962 children enrolled in the Boston Birth Cohort (BBC): 235 children with severe LRTIs and 2,333 controls. They used Kaplan-Meier survival estimates and Cox proportional hazards models to evaluate the risk of OSA.

jujeleviclepridrebroclesahefroceswuthucrapristimiwecaspuwosouepauitetulusposleclubrimaswustomepruriwristarephogawrabrawethubashuspephiswegehubrasowrimuphidacresispithejurowrerojakethejustevajedrulaslutashodawrewivocl

Compared with patients with severe LRTIs, controls were more likely to have been full-term births, delivered vaginally, and breastfed. The OSA rate was significantly higher among children with severe LRTIs compared with controls (14.7% vs 6.8%). In the adjusted model controlling for relevant maternal and infant covariables, severe LRTI was significantly associated with increased OSA risk (HR, 2.06; 95% CI, 1.41-3.02; P < .001). Other factors such as prematurity (HR, 1.34; 95% CI, 1.01-1.77; P = .039) and maternal obesity (HR, 1.82; 95% CI, 1.32-2.52; P < .001) were also associated with increased OSA risk.

Maria Gutierrez, MD, of the Division of Pediatric Allergy, Immunology, and Rheumatology at Johns Hopkins University School of Medicine in Baltimore led the research. The study was published in Pediatric Pulmonology (2023 Dec 2. doi: 10.1002/ppul.26810). Study limitations included the use of electronic medical record data and potential lack of generalizability. The BBC is supported by the NIH.

– Agnes S. Montgomery, MD

Fellow-in-Training


References

1. Gayoso-Liviac MG, Nino G, Montgomery AS, Hong X, Wang X, Gutierrez MJ. Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea. Pediatr Pulmonol. 2024;59:679-687.

2. Snow A, Dayyat E, Montgomery‐Downs HE, Kheirandish‐Gozal L, Gozal D. Pediatric obstructive sleep apnea: a potential late consequence of respiratory syncytial virus bronchiolitis. Pediatr Pulmonol. 2009;44(12):1186‐1191.

3. Chen VC‐H, Yang Y‐H, Kuo T‐Y, et al. Increased incidence of obstructive sleep apnea in hospitalized children after enterovirus infection: a nationwide population‐based cohort study. Pediatr Infect Dis J. 2018;37(9):872‐879.

4. Gutierrez MJ, Nino G, Landeo‐Gutierrez JS, et al. Lower respiratory tract infections in early life are associated with obstructive sleep apnea diagnosis during childhood in a large birth cohort. Sleep. 2021;44:12.
 

AIRWAYS DISORDERS NETWORK

Pediatric Chest Medicine Section

Children with severe lower respiratory tract infections (LRTIs) within the first 2 years of life had a 2.06-fold increased risk of developing pediatric OSA by age 5, according to a study comparing patients hospitalized with LRTI to controls without severe LRTI.¹ Prior studies linked LRTI and OSA, but the impact of LRTI severity was unknown.^2,3,4Using a case-control design, researchers analyzed data from 2,962 children enrolled in the Boston Birth Cohort (BBC): 235 children with severe LRTIs and 2,333 controls. They used Kaplan-Meier survival estimates and Cox proportional hazards models to evaluate the risk of OSA.

jujeleviclepridrebroclesahefroceswuthucrapristimiwecaspuwosouepauitetulusposleclubrimaswustomepruriwristarephogawrabrawethubashuspephiswegehubrasowrimuphidacresispithejurowrerojakethejustevajedrulaslutashodawrewivocl

Compared with patients with severe LRTIs, controls were more likely to have been full-term births, delivered vaginally, and breastfed. The OSA rate was significantly higher among children with severe LRTIs compared with controls (14.7% vs 6.8%). In the adjusted model controlling for relevant maternal and infant covariables, severe LRTI was significantly associated with increased OSA risk (HR, 2.06; 95% CI, 1.41-3.02; P < .001). Other factors such as prematurity (HR, 1.34; 95% CI, 1.01-1.77; P = .039) and maternal obesity (HR, 1.82; 95% CI, 1.32-2.52; P < .001) were also associated with increased OSA risk.

Maria Gutierrez, MD, of the Division of Pediatric Allergy, Immunology, and Rheumatology at Johns Hopkins University School of Medicine in Baltimore led the research. The study was published in Pediatric Pulmonology (2023 Dec 2. doi: 10.1002/ppul.26810). Study limitations included the use of electronic medical record data and potential lack of generalizability. The BBC is supported by the NIH.

– Agnes S. Montgomery, MD

Fellow-in-Training


References

1. Gayoso-Liviac MG, Nino G, Montgomery AS, Hong X, Wang X, Gutierrez MJ. Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea. Pediatr Pulmonol. 2024;59:679-687.

2. Snow A, Dayyat E, Montgomery‐Downs HE, Kheirandish‐Gozal L, Gozal D. Pediatric obstructive sleep apnea: a potential late consequence of respiratory syncytial virus bronchiolitis. Pediatr Pulmonol. 2009;44(12):1186‐1191.

3. Chen VC‐H, Yang Y‐H, Kuo T‐Y, et al. Increased incidence of obstructive sleep apnea in hospitalized children after enterovirus infection: a nationwide population‐based cohort study. Pediatr Infect Dis J. 2018;37(9):872‐879.

4. Gutierrez MJ, Nino G, Landeo‐Gutierrez JS, et al. Lower respiratory tract infections in early life are associated with obstructive sleep apnea diagnosis during childhood in a large birth cohort. Sleep. 2021;44:12.
 

AIRWAYS DISORDERS NETWORK

Pediatric Chest Medicine Section

Children with severe lower respiratory tract infections (LRTIs) within the first 2 years of life had a 2.06-fold increased risk of developing pediatric OSA by age 5, according to a study comparing patients hospitalized with LRTI to controls without severe LRTI.¹ Prior studies linked LRTI and OSA, but the impact of LRTI severity was unknown.^2,3,4Using a case-control design, researchers analyzed data from 2,962 children enrolled in the Boston Birth Cohort (BBC): 235 children with severe LRTIs and 2,333 controls. They used Kaplan-Meier survival estimates and Cox proportional hazards models to evaluate the risk of OSA.

jujeleviclepridrebroclesahefroceswuthucrapristimiwecaspuwosouepauitetulusposleclubrimaswustomepruriwristarephogawrabrawethubashuspephiswegehubrasowrimuphidacresispithejurowrerojakethejustevajedrulaslutashodawrewivocl

Compared with patients with severe LRTIs, controls were more likely to have been full-term births, delivered vaginally, and breastfed. The OSA rate was significantly higher among children with severe LRTIs compared with controls (14.7% vs 6.8%). In the adjusted model controlling for relevant maternal and infant covariables, severe LRTI was significantly associated with increased OSA risk (HR, 2.06; 95% CI, 1.41-3.02; P < .001). Other factors such as prematurity (HR, 1.34; 95% CI, 1.01-1.77; P = .039) and maternal obesity (HR, 1.82; 95% CI, 1.32-2.52; P < .001) were also associated with increased OSA risk.

Maria Gutierrez, MD, of the Division of Pediatric Allergy, Immunology, and Rheumatology at Johns Hopkins University School of Medicine in Baltimore led the research. The study was published in Pediatric Pulmonology (2023 Dec 2. doi: 10.1002/ppul.26810). Study limitations included the use of electronic medical record data and potential lack of generalizability. The BBC is supported by the NIH.

– Agnes S. Montgomery, MD

Fellow-in-Training


References

1. Gayoso-Liviac MG, Nino G, Montgomery AS, Hong X, Wang X, Gutierrez MJ. Infants hospitalized with lower respiratory tract infections during the first two years of life have increased risk of pediatric obstructive sleep apnea. Pediatr Pulmonol. 2024;59:679-687.

2. Snow A, Dayyat E, Montgomery‐Downs HE, Kheirandish‐Gozal L, Gozal D. Pediatric obstructive sleep apnea: a potential late consequence of respiratory syncytial virus bronchiolitis. Pediatr Pulmonol. 2009;44(12):1186‐1191.

3. Chen VC‐H, Yang Y‐H, Kuo T‐Y, et al. Increased incidence of obstructive sleep apnea in hospitalized children after enterovirus infection: a nationwide population‐based cohort study. Pediatr Infect Dis J. 2018;37(9):872‐879.

4. Gutierrez MJ, Nino G, Landeo‐Gutierrez JS, et al. Lower respiratory tract infections in early life are associated with obstructive sleep apnea diagnosis during childhood in a large birth cohort. Sleep. 2021;44:12.
 

The National institutes of Health will soon start a clinical trial in an attempt to find potential treatments for symptoms of long COVID, focusing on sleep disturbances, problems with exercise, and post-exertional malaise. 

The trials will look to enroll more than 1,500 people across 50 study sites to tackle some of the most common symptoms of long COVID. 

“When people can’t get reliable sleep, can’t exert themselves and feel sick following tasks that used to be simple, the physical and mental anguish can lead to feelings of utter helplessness,” Walter J. Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, said in a statement. “We urgently need to come up with answers to help those struggling with long COVID feel whole again.”

The new trials will be part of the NIH’s Researching COVID to Enhance Recovery initiative, known as RECOVER. Since beginning enrollment in July 2023 for four trials, RECOVER now features eight trials across the country looking at all parts of long COVID. RECOVER is part of a $1.15 billion nationwide program that Congress approved in 2020 for the NIH to research and test treatments for long COVID. 

While focused on sleep disturbances, the trial will test two Food and Drug Administration–approved drugs currently used to treat people with hypersomnia. There will also be a trial to test if melatonin helps people with long COVID-related sleep problems. Light therapy will also be tested. 

The trials that deal with problems people have had with exercise will focus on personalized cardiopulmonary rehabilitation, where patients experiment with exercise training, strength and flexibility training, education, and social support. 

Another trial will look at structured pacing, which is designed to help people with exercise problems identify, control, and ease long COVID symptoms.

A version of this article appeared on WebMD.com.

The National institutes of Health will soon start a clinical trial in an attempt to find potential treatments for symptoms of long COVID, focusing on sleep disturbances, problems with exercise, and post-exertional malaise. 

The trials will look to enroll more than 1,500 people across 50 study sites to tackle some of the most common symptoms of long COVID. 

“When people can’t get reliable sleep, can’t exert themselves and feel sick following tasks that used to be simple, the physical and mental anguish can lead to feelings of utter helplessness,” Walter J. Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, said in a statement. “We urgently need to come up with answers to help those struggling with long COVID feel whole again.”

The new trials will be part of the NIH’s Researching COVID to Enhance Recovery initiative, known as RECOVER. Since beginning enrollment in July 2023 for four trials, RECOVER now features eight trials across the country looking at all parts of long COVID. RECOVER is part of a $1.15 billion nationwide program that Congress approved in 2020 for the NIH to research and test treatments for long COVID. 

While focused on sleep disturbances, the trial will test two Food and Drug Administration–approved drugs currently used to treat people with hypersomnia. There will also be a trial to test if melatonin helps people with long COVID-related sleep problems. Light therapy will also be tested. 

The trials that deal with problems people have had with exercise will focus on personalized cardiopulmonary rehabilitation, where patients experiment with exercise training, strength and flexibility training, education, and social support. 

Another trial will look at structured pacing, which is designed to help people with exercise problems identify, control, and ease long COVID symptoms.

A version of this article appeared on WebMD.com.

The National institutes of Health will soon start a clinical trial in an attempt to find potential treatments for symptoms of long COVID, focusing on sleep disturbances, problems with exercise, and post-exertional malaise. 

The trials will look to enroll more than 1,500 people across 50 study sites to tackle some of the most common symptoms of long COVID. 

“When people can’t get reliable sleep, can’t exert themselves and feel sick following tasks that used to be simple, the physical and mental anguish can lead to feelings of utter helplessness,” Walter J. Koroshetz, MD, director of the NIH’s National Institute of Neurological Disorders and Stroke, said in a statement. “We urgently need to come up with answers to help those struggling with long COVID feel whole again.”

The new trials will be part of the NIH’s Researching COVID to Enhance Recovery initiative, known as RECOVER. Since beginning enrollment in July 2023 for four trials, RECOVER now features eight trials across the country looking at all parts of long COVID. RECOVER is part of a $1.15 billion nationwide program that Congress approved in 2020 for the NIH to research and test treatments for long COVID. 

While focused on sleep disturbances, the trial will test two Food and Drug Administration–approved drugs currently used to treat people with hypersomnia. There will also be a trial to test if melatonin helps people with long COVID-related sleep problems. Light therapy will also be tested. 

The trials that deal with problems people have had with exercise will focus on personalized cardiopulmonary rehabilitation, where patients experiment with exercise training, strength and flexibility training, education, and social support. 

Another trial will look at structured pacing, which is designed to help people with exercise problems identify, control, and ease long COVID symptoms.

A version of this article appeared on WebMD.com.

TOPLINE:

Healthier sleep is associated with lower odds of developing a wide range of gastrointestinal conditions, regardless of genetic susceptibility, new research revealed.

METHODOLOGY:

• Due to the widespread prevalence of sleep issues and a growing burden of digestive diseases globally, researchers investigated the association between sleep quality and digestive disorders in a prospective cohort study of 410,586 people in the UK Biobank.
• Five individual sleep behaviors were assessed: sleep duration, insomnia, snoring, daytime sleepiness, and chronotype.
• A healthy sleep was defined as a morning chronotype, 7-8 hours of sleep duration, no self-reported snoring, never or rare insomnia, and a low frequency of daytime sleepiness, for a score of 5/5.
• The study investigators tracked the development of 16 digestive diseases over a mean period of 13.2 years.
• As well as looking at healthy sleep scores, researchers considered genetic susceptibility to gastrointestinal conditions.

TAKEAWAY:

• Participants with a healthy sleep score had 28% lower odds of developing any digestive disease (hazard ratio [HR], 0.72; 95% CI, 0.69-0.75) than those with a sleep score of 0/1.
• Of the 16 digestive diseases looked at, the reduction of risk was highest for irritable bowel syndrome at 50% (HR, 0.50; 95% CI, 0.45-0.57).
• A healthy sleep score was also associated with 37% reduced odds for metabolic dysfunction–associated steatotic liver disease (formerly known as nonalcoholic fatty liver disease; HR, 0.63; 95% CI, 0.55-0.71), 35% lower chance for peptic ulcer (HR, 0.65; 95% CI, 0.058-0.74), 34% reduced chance for dyspepsia (HR, 0.66; 95% CI, 0.58-0.75), and a 25% lower risk for diverticulosis (HR, 0.75; 95% CI, 0.71-0.80).
• High genetic risk and poor sleep scores were also associated with increased odds (53% to > 200%) of developing digestive diseases.
• However, healthy sleep reduced the risk for digestive diseases regardless of genetic susceptibility.

IN PRACTICE:

“Our findings underscore the potential holistic impact of different sleep behaviors in mitigating the risk of digestive diseases in clinical practice,” wrote Shiyi Yu, MD, of Guangdong Provincial People’s Hospital, Guangzhou, Guangdong, China, and colleagues.

Poor sleep can also change our gut microbiome, Dr. Yu told this news organization. If you don’t sleep well, the repair of the gut lining cannot be finished during the night.

SOURCE:

The study was presented at the Digestive Disease Week® (DDW), 2024, annual meeting.

DISCLOSURES:

Dr. Yu had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Healthier sleep is associated with lower odds of developing a wide range of gastrointestinal conditions, regardless of genetic susceptibility, new research revealed.

METHODOLOGY:

• Due to the widespread prevalence of sleep issues and a growing burden of digestive diseases globally, researchers investigated the association between sleep quality and digestive disorders in a prospective cohort study of 410,586 people in the UK Biobank.
• Five individual sleep behaviors were assessed: sleep duration, insomnia, snoring, daytime sleepiness, and chronotype.
• A healthy sleep was defined as a morning chronotype, 7-8 hours of sleep duration, no self-reported snoring, never or rare insomnia, and a low frequency of daytime sleepiness, for a score of 5/5.
• The study investigators tracked the development of 16 digestive diseases over a mean period of 13.2 years.
• As well as looking at healthy sleep scores, researchers considered genetic susceptibility to gastrointestinal conditions.

TAKEAWAY:

• Participants with a healthy sleep score had 28% lower odds of developing any digestive disease (hazard ratio [HR], 0.72; 95% CI, 0.69-0.75) than those with a sleep score of 0/1.
• Of the 16 digestive diseases looked at, the reduction of risk was highest for irritable bowel syndrome at 50% (HR, 0.50; 95% CI, 0.45-0.57).
• A healthy sleep score was also associated with 37% reduced odds for metabolic dysfunction–associated steatotic liver disease (formerly known as nonalcoholic fatty liver disease; HR, 0.63; 95% CI, 0.55-0.71), 35% lower chance for peptic ulcer (HR, 0.65; 95% CI, 0.058-0.74), 34% reduced chance for dyspepsia (HR, 0.66; 95% CI, 0.58-0.75), and a 25% lower risk for diverticulosis (HR, 0.75; 95% CI, 0.71-0.80).
• High genetic risk and poor sleep scores were also associated with increased odds (53% to > 200%) of developing digestive diseases.
• However, healthy sleep reduced the risk for digestive diseases regardless of genetic susceptibility.

IN PRACTICE:

“Our findings underscore the potential holistic impact of different sleep behaviors in mitigating the risk of digestive diseases in clinical practice,” wrote Shiyi Yu, MD, of Guangdong Provincial People’s Hospital, Guangzhou, Guangdong, China, and colleagues.

Poor sleep can also change our gut microbiome, Dr. Yu told this news organization. If you don’t sleep well, the repair of the gut lining cannot be finished during the night.

SOURCE:

The study was presented at the Digestive Disease Week® (DDW), 2024, annual meeting.

DISCLOSURES:

Dr. Yu had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Healthier sleep is associated with lower odds of developing a wide range of gastrointestinal conditions, regardless of genetic susceptibility, new research revealed.

METHODOLOGY:

• Due to the widespread prevalence of sleep issues and a growing burden of digestive diseases globally, researchers investigated the association between sleep quality and digestive disorders in a prospective cohort study of 410,586 people in the UK Biobank.
• Five individual sleep behaviors were assessed: sleep duration, insomnia, snoring, daytime sleepiness, and chronotype.
• A healthy sleep was defined as a morning chronotype, 7-8 hours of sleep duration, no self-reported snoring, never or rare insomnia, and a low frequency of daytime sleepiness, for a score of 5/5.
• The study investigators tracked the development of 16 digestive diseases over a mean period of 13.2 years.
• As well as looking at healthy sleep scores, researchers considered genetic susceptibility to gastrointestinal conditions.

TAKEAWAY:

• Participants with a healthy sleep score had 28% lower odds of developing any digestive disease (hazard ratio [HR], 0.72; 95% CI, 0.69-0.75) than those with a sleep score of 0/1.
• Of the 16 digestive diseases looked at, the reduction of risk was highest for irritable bowel syndrome at 50% (HR, 0.50; 95% CI, 0.45-0.57).
• A healthy sleep score was also associated with 37% reduced odds for metabolic dysfunction–associated steatotic liver disease (formerly known as nonalcoholic fatty liver disease; HR, 0.63; 95% CI, 0.55-0.71), 35% lower chance for peptic ulcer (HR, 0.65; 95% CI, 0.058-0.74), 34% reduced chance for dyspepsia (HR, 0.66; 95% CI, 0.58-0.75), and a 25% lower risk for diverticulosis (HR, 0.75; 95% CI, 0.71-0.80).
• High genetic risk and poor sleep scores were also associated with increased odds (53% to > 200%) of developing digestive diseases.
• However, healthy sleep reduced the risk for digestive diseases regardless of genetic susceptibility.

IN PRACTICE:

“Our findings underscore the potential holistic impact of different sleep behaviors in mitigating the risk of digestive diseases in clinical practice,” wrote Shiyi Yu, MD, of Guangdong Provincial People’s Hospital, Guangzhou, Guangdong, China, and colleagues.

Poor sleep can also change our gut microbiome, Dr. Yu told this news organization. If you don’t sleep well, the repair of the gut lining cannot be finished during the night.

SOURCE:

The study was presented at the Digestive Disease Week® (DDW), 2024, annual meeting.

DISCLOSURES:

Dr. Yu had no relevant financial disclosures.

A version of this article appeared on Medscape.com.

A few months ago, I posted a column on continuous positive airway pressure (CPAP) with the title, “CPAP Oversells and Underperforms.” To date, it has 299 likes and 90 comments, which are almost all negative. I’m glad to see that it’s generated interest, and I’d like to address some of the themes expressed in the posts.

Most comments were personal testimonies to the miracles of CPAP. These are important, and the point deserves emphasis. CPAP can provide significant improvements in daytime sleepiness and quality of life. I closed the original piece by acknowledging this important fact. Readers can be forgiven for missing it given that the title and text were otherwise disparaging of CPAP.

But several comments warrant a more in-depth discussion. The original piece focuses on CPAP and cardiovascular (CV) outcomes but made no mention of atrial fibrillation (AF) or ejection fraction (EF). The effects of CPAP on each are touted by cardiologists and PAP-pushers alike and are drivers of frequent referrals. It›s my fault for omitting them from the discussion.

AF is easy. The data is identical to all other things CPAP and CV. Based on biologic plausibility alone, the likelihood of a relationship between AF and obstructive sleep apnea (OSA) is similar to the odds that the Celtics raise an 18th banner come June. There’s hypoxia, intrathoracic pressure swings, sympathetic surges, and sleep state disruptions. It’s easy to get from there to arrhythmogenesis. There’s lots of observational noise, too, but no randomized proof that CPAP alters this relationship.

I found four randomized controlled trials (RCTs) that tested CPAP’s effect on AF. I’ll save you the suspense; they were all negative. One even found a signal for more adverse events in the CPAP group. These studies have several positive qualities: They enrolled patients with moderate to severe sleep apnea and high oxygen desaturation indices, adherence averaged more than 4 hours across all groups in all trials, and the methods for assessing the AF outcomes differed slightly. There’s also a lot not to like: The sample sizes were small, only one trial enrolled “sleepy” patients (as assessed by the Epworth Sleepiness Score), and follow-up was short.

To paraphrase Carl Sagan, “absence of evidence does not equal evidence of absence.” As a statistician would say, type II error cannot be excluded by these RCTs. In medicine, however, the burden of proof falls on demonstrating efficacy. If we treat before concluding that a therapy works, we risk wasting time, money, medical resources, and the most precious of patient commodities: the energy required for behavior change. In their response to letters to the editor, the authors of the third RCT summarize the CPAP, AF, and CV disease data far better than I ever could. They sound the same words of caution and come out against screening patients with AF for OSA. 

The story for CPAP’s effects on EF is similar though muddier. The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for heart failure cite a meta-analysis showing that CPAP improves left ventricular EF. In 2019, the American Academy of Sleep Medicine (AASM) CPAP guidelines included a systematic review and meta-analysis that found that CPAP has no effect on left ventricular EF in patients with or without heart failure.

There are a million reasons why two systematic reviews on the same topic might come to different conclusions. In this case, the included studies only partially overlap, and broadly speaking, it appears the authors made trade-offs. The review cited by the ACC/AHA had broader inclusion and significantly more patients and paid for it in heterogeneity (I2 in the 80%-90% range). The AASM analysis achieved 0% heterogeneity but limited inclusion to fewer than 100 patients. Across both, the improvement in EF was 2%- 5% at a minimally clinically important difference of 4%. Hardly convincing.

In summary, the road to negative trials and patient harm has always been paved with observational signal and biologic plausibility. Throw in some intellectual and academic bias, and you’ve created the perfect storm of therapeutic overconfidence. The cemetery for discarded medical therapies is crowded, but there’s room for CPAP, at least when it comes to using it to improve CV outcomes. 
 

Dr. Holley is a professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a physician at Pulmonary/Sleep and Critical Care Medicine, MedStar Washington Hospital Center, Washington. He disclosed ties to Metapharm Inc., CHEST College, and WebMD.

A version of this article appeared on Medscape.com .

A few months ago, I posted a column on continuous positive airway pressure (CPAP) with the title, “CPAP Oversells and Underperforms.” To date, it has 299 likes and 90 comments, which are almost all negative. I’m glad to see that it’s generated interest, and I’d like to address some of the themes expressed in the posts.

Most comments were personal testimonies to the miracles of CPAP. These are important, and the point deserves emphasis. CPAP can provide significant improvements in daytime sleepiness and quality of life. I closed the original piece by acknowledging this important fact. Readers can be forgiven for missing it given that the title and text were otherwise disparaging of CPAP.

But several comments warrant a more in-depth discussion. The original piece focuses on CPAP and cardiovascular (CV) outcomes but made no mention of atrial fibrillation (AF) or ejection fraction (EF). The effects of CPAP on each are touted by cardiologists and PAP-pushers alike and are drivers of frequent referrals. It›s my fault for omitting them from the discussion.

AF is easy. The data is identical to all other things CPAP and CV. Based on biologic plausibility alone, the likelihood of a relationship between AF and obstructive sleep apnea (OSA) is similar to the odds that the Celtics raise an 18th banner come June. There’s hypoxia, intrathoracic pressure swings, sympathetic surges, and sleep state disruptions. It’s easy to get from there to arrhythmogenesis. There’s lots of observational noise, too, but no randomized proof that CPAP alters this relationship.

I found four randomized controlled trials (RCTs) that tested CPAP’s effect on AF. I’ll save you the suspense; they were all negative. One even found a signal for more adverse events in the CPAP group. These studies have several positive qualities: They enrolled patients with moderate to severe sleep apnea and high oxygen desaturation indices, adherence averaged more than 4 hours across all groups in all trials, and the methods for assessing the AF outcomes differed slightly. There’s also a lot not to like: The sample sizes were small, only one trial enrolled “sleepy” patients (as assessed by the Epworth Sleepiness Score), and follow-up was short.

To paraphrase Carl Sagan, “absence of evidence does not equal evidence of absence.” As a statistician would say, type II error cannot be excluded by these RCTs. In medicine, however, the burden of proof falls on demonstrating efficacy. If we treat before concluding that a therapy works, we risk wasting time, money, medical resources, and the most precious of patient commodities: the energy required for behavior change. In their response to letters to the editor, the authors of the third RCT summarize the CPAP, AF, and CV disease data far better than I ever could. They sound the same words of caution and come out against screening patients with AF for OSA. 

The story for CPAP’s effects on EF is similar though muddier. The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for heart failure cite a meta-analysis showing that CPAP improves left ventricular EF. In 2019, the American Academy of Sleep Medicine (AASM) CPAP guidelines included a systematic review and meta-analysis that found that CPAP has no effect on left ventricular EF in patients with or without heart failure.

There are a million reasons why two systematic reviews on the same topic might come to different conclusions. In this case, the included studies only partially overlap, and broadly speaking, it appears the authors made trade-offs. The review cited by the ACC/AHA had broader inclusion and significantly more patients and paid for it in heterogeneity (I2 in the 80%-90% range). The AASM analysis achieved 0% heterogeneity but limited inclusion to fewer than 100 patients. Across both, the improvement in EF was 2%- 5% at a minimally clinically important difference of 4%. Hardly convincing.

In summary, the road to negative trials and patient harm has always been paved with observational signal and biologic plausibility. Throw in some intellectual and academic bias, and you’ve created the perfect storm of therapeutic overconfidence. The cemetery for discarded medical therapies is crowded, but there’s room for CPAP, at least when it comes to using it to improve CV outcomes. 
 

Dr. Holley is a professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a physician at Pulmonary/Sleep and Critical Care Medicine, MedStar Washington Hospital Center, Washington. He disclosed ties to Metapharm Inc., CHEST College, and WebMD.

A version of this article appeared on Medscape.com .

A few months ago, I posted a column on continuous positive airway pressure (CPAP) with the title, “CPAP Oversells and Underperforms.” To date, it has 299 likes and 90 comments, which are almost all negative. I’m glad to see that it’s generated interest, and I’d like to address some of the themes expressed in the posts.

Most comments were personal testimonies to the miracles of CPAP. These are important, and the point deserves emphasis. CPAP can provide significant improvements in daytime sleepiness and quality of life. I closed the original piece by acknowledging this important fact. Readers can be forgiven for missing it given that the title and text were otherwise disparaging of CPAP.

But several comments warrant a more in-depth discussion. The original piece focuses on CPAP and cardiovascular (CV) outcomes but made no mention of atrial fibrillation (AF) or ejection fraction (EF). The effects of CPAP on each are touted by cardiologists and PAP-pushers alike and are drivers of frequent referrals. It›s my fault for omitting them from the discussion.

AF is easy. The data is identical to all other things CPAP and CV. Based on biologic plausibility alone, the likelihood of a relationship between AF and obstructive sleep apnea (OSA) is similar to the odds that the Celtics raise an 18th banner come June. There’s hypoxia, intrathoracic pressure swings, sympathetic surges, and sleep state disruptions. It’s easy to get from there to arrhythmogenesis. There’s lots of observational noise, too, but no randomized proof that CPAP alters this relationship.

I found four randomized controlled trials (RCTs) that tested CPAP’s effect on AF. I’ll save you the suspense; they were all negative. One even found a signal for more adverse events in the CPAP group. These studies have several positive qualities: They enrolled patients with moderate to severe sleep apnea and high oxygen desaturation indices, adherence averaged more than 4 hours across all groups in all trials, and the methods for assessing the AF outcomes differed slightly. There’s also a lot not to like: The sample sizes were small, only one trial enrolled “sleepy” patients (as assessed by the Epworth Sleepiness Score), and follow-up was short.

To paraphrase Carl Sagan, “absence of evidence does not equal evidence of absence.” As a statistician would say, type II error cannot be excluded by these RCTs. In medicine, however, the burden of proof falls on demonstrating efficacy. If we treat before concluding that a therapy works, we risk wasting time, money, medical resources, and the most precious of patient commodities: the energy required for behavior change. In their response to letters to the editor, the authors of the third RCT summarize the CPAP, AF, and CV disease data far better than I ever could. They sound the same words of caution and come out against screening patients with AF for OSA. 

The story for CPAP’s effects on EF is similar though muddier. The American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for heart failure cite a meta-analysis showing that CPAP improves left ventricular EF. In 2019, the American Academy of Sleep Medicine (AASM) CPAP guidelines included a systematic review and meta-analysis that found that CPAP has no effect on left ventricular EF in patients with or without heart failure.

There are a million reasons why two systematic reviews on the same topic might come to different conclusions. In this case, the included studies only partially overlap, and broadly speaking, it appears the authors made trade-offs. The review cited by the ACC/AHA had broader inclusion and significantly more patients and paid for it in heterogeneity (I2 in the 80%-90% range). The AASM analysis achieved 0% heterogeneity but limited inclusion to fewer than 100 patients. Across both, the improvement in EF was 2%- 5% at a minimally clinically important difference of 4%. Hardly convincing.

In summary, the road to negative trials and patient harm has always been paved with observational signal and biologic plausibility. Throw in some intellectual and academic bias, and you’ve created the perfect storm of therapeutic overconfidence. The cemetery for discarded medical therapies is crowded, but there’s room for CPAP, at least when it comes to using it to improve CV outcomes. 
 

Dr. Holley is a professor in the department of medicine, Uniformed Services University, Bethesda, Maryland, and a physician at Pulmonary/Sleep and Critical Care Medicine, MedStar Washington Hospital Center, Washington. He disclosed ties to Metapharm Inc., CHEST College, and WebMD.

A version of this article appeared on Medscape.com .