Sleep Medicine

TOPLINE:

Indicators of early bone loss were significantly higher in adults with severe obstructive sleep apnea (OSA) than in those with mild or moderate OSA and controls.

METHODOLOGY:

• The researchers enrolled 90 men aged 30-59 years who were patients at a single sleep and respiratory center between August 2017 and February 2019; the average age was 47.1 years, and the average body mass index was 25.7 kg/m².
• The study population included 25 individuals with mild OSA, 21 with moderate OSA, 34 with severe OSA, and 10 controls without OSA.
• Bone loss was assessed using high-resolution peripheral quantitative computed tomography and blood samples. The researchers collected information on metabolic and inflammatory bone turnover indicators, as well as bone geometric parameters, bone microstructure parameters, and measures of bone mineral density (BMD).

TAKEAWAY:

• Total volumetric bone mineral density was significantly lower in patients with OSA than in controls and significantly different among OSA groups, as were the meta trabecular volumetric BMD, trabecular thickness (Tb.Th), and cortical thickness (Ct.Th).
• Differences in bone microstructure between patients with OSA and controls were most evident in measures of Tb.Th and Ct.Th.
• No significant differences appeared in blood bone turnover indicators or inflammation indicators among the groups.

IN PRACTICE:

“A study with a larger sample is necessary to further assess the relationship and mechanisms between OSA and osteoporosis,” the researchers wrote. 

SOURCE:

The lead author on the study was Yixian Qiao, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. The study was published online in BMC Pulmonary Medicine.

LIMITATIONS:

The cross-sectional design, small sample size, and inability to control for several key confounders such as nutritional status and amount of exercise, as well as the exclusion of women and elderly individuals, limited the findings.

DISCLOSURES:

The study was supported by the National Key Research and Development Projects of China. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Indicators of early bone loss were significantly higher in adults with severe obstructive sleep apnea (OSA) than in those with mild or moderate OSA and controls.

METHODOLOGY:

• The researchers enrolled 90 men aged 30-59 years who were patients at a single sleep and respiratory center between August 2017 and February 2019; the average age was 47.1 years, and the average body mass index was 25.7 kg/m².
• The study population included 25 individuals with mild OSA, 21 with moderate OSA, 34 with severe OSA, and 10 controls without OSA.
• Bone loss was assessed using high-resolution peripheral quantitative computed tomography and blood samples. The researchers collected information on metabolic and inflammatory bone turnover indicators, as well as bone geometric parameters, bone microstructure parameters, and measures of bone mineral density (BMD).

TAKEAWAY:

• Total volumetric bone mineral density was significantly lower in patients with OSA than in controls and significantly different among OSA groups, as were the meta trabecular volumetric BMD, trabecular thickness (Tb.Th), and cortical thickness (Ct.Th).
• Differences in bone microstructure between patients with OSA and controls were most evident in measures of Tb.Th and Ct.Th.
• No significant differences appeared in blood bone turnover indicators or inflammation indicators among the groups.

IN PRACTICE:

“A study with a larger sample is necessary to further assess the relationship and mechanisms between OSA and osteoporosis,” the researchers wrote. 

SOURCE:

The lead author on the study was Yixian Qiao, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. The study was published online in BMC Pulmonary Medicine.

LIMITATIONS:

The cross-sectional design, small sample size, and inability to control for several key confounders such as nutritional status and amount of exercise, as well as the exclusion of women and elderly individuals, limited the findings.

DISCLOSURES:

The study was supported by the National Key Research and Development Projects of China. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Indicators of early bone loss were significantly higher in adults with severe obstructive sleep apnea (OSA) than in those with mild or moderate OSA and controls.

METHODOLOGY:

• The researchers enrolled 90 men aged 30-59 years who were patients at a single sleep and respiratory center between August 2017 and February 2019; the average age was 47.1 years, and the average body mass index was 25.7 kg/m².
• The study population included 25 individuals with mild OSA, 21 with moderate OSA, 34 with severe OSA, and 10 controls without OSA.
• Bone loss was assessed using high-resolution peripheral quantitative computed tomography and blood samples. The researchers collected information on metabolic and inflammatory bone turnover indicators, as well as bone geometric parameters, bone microstructure parameters, and measures of bone mineral density (BMD).

TAKEAWAY:

• Total volumetric bone mineral density was significantly lower in patients with OSA than in controls and significantly different among OSA groups, as were the meta trabecular volumetric BMD, trabecular thickness (Tb.Th), and cortical thickness (Ct.Th).
• Differences in bone microstructure between patients with OSA and controls were most evident in measures of Tb.Th and Ct.Th.
• No significant differences appeared in blood bone turnover indicators or inflammation indicators among the groups.

IN PRACTICE:

“A study with a larger sample is necessary to further assess the relationship and mechanisms between OSA and osteoporosis,” the researchers wrote. 

SOURCE:

The lead author on the study was Yixian Qiao, MD, of the Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. The study was published online in BMC Pulmonary Medicine.

LIMITATIONS:

The cross-sectional design, small sample size, and inability to control for several key confounders such as nutritional status and amount of exercise, as well as the exclusion of women and elderly individuals, limited the findings.

DISCLOSURES:

The study was supported by the National Key Research and Development Projects of China. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) have overlapping neurologic symptoms — particularly profound fatigue. The similarity between these two conditions has led to the question of whether they are indeed distinct central nervous system (CNS) entities, or whether they exist along a spectrum and are actually two different manifestations of the same disease process.

A new study utilized a novel methodology — unbiased quantitative mass spectrometry-based proteomics — to investigate this question by analyzing cerebrospinal fluid (CSF) in a group of patients with ME/CFS and another group of patients diagnosed with both ME/CFS and FM.

Close to 2,100 proteins were identified, of which nearly 1,800 were common to both conditions.

“ME/CFS and fibromyalgia do not appear to be distinct entities, with respect to their cerebrospinal fluid proteins,” lead author Steven Schutzer, MD, professor of medicine, Rutgers New Jersey School of Medicine, told this news organization.

“Work is underway to solve the multiple mysteries of ME/CFS, fibromyalgia, and other neurologic-associated diseases,” he continued. “We have further affirmed that we have a precise objective discovery tool in our hands. Collectively studying multiple diseases brings clarity to each individual disease.”

The study was published in the December 2023 issue of Annals of Medicine.
 

Cutting-Edge Technology

“ME/CFS is characterized by disabling fatigue, and FM is an illness characterized by body-wide pain,” Dr. Schutzer said. These “medically unexplained” illnesses often coexist by current definitions, and the overlap between them has suggested that they may be part of the “same illness spectrum.”

But co-investigator Benjamin Natelson, MD, professor of neurology and director of the Pain and Fatigue Study Center, Mount Sinai, New York, and others found in previous research that there are distinct differences between the conditions, raising the possibility that there may be different pathophysiological processes.

“The physicians and scientists on our team have had longstanding interest in studying neurologic diseases with cutting-edge tools such as mass spectrometry applied to CSF,” Dr. Schutzer said. “We have had success using this message to distinguish diseases such as ME/CFS from post-treatment Lyme disease, multiple sclerosis, and healthy normal people.”

Dr. Schutzer explained that Dr. Natelson had acquired CSF samples from “well-characterized [ME/CFS] patients and controls.”

Since the cause of ME/CFS is “unknown,” it seemed “ripe to investigate it further with the discovery tool of mass spectrometry” by harnessing the “most advanced equipment in the country at the pacific Northwest National Laboratory, which is part of the US Department of Energy.”

Dr. Schutzer noted that it was the “merger of different clinical and laboratory expertise” that enabled them to address whether ME/CFS and FM are two distinct disease processes.

The choice of analyzing CSF is that it’s the fluid closest to the brain, he added. “A lot of people have studied ME/CFS peripherally because they don’t have access to spinal fluid or it’s easier to look peripherally in the blood, but that doesn’t mean that the blood is where the real ‘action’ is occurring.”

The researchers compared the CSF of 15 patients with ME/CFS only to 15 patients with ME/CFS+FM using mass spectrometry-based proteomics, which they had employed in previous research to see whether ME/CFS was distinct from persistent neurologic Lyme disease syndrome.

This technology has become the “method of choice and discovery tool to rapidly uncover protein biomarkers that can distinguish one disease from another,” the authors stated.

In particular, in unbiased quantitative mass spectrometry-based proteomics, the researchers do not have to know in advance what’s in a sample before studying it, Dr. Schutzer explained.
 

Shared Pathophysiology?

Both groups of patients were of similar age (41.3 ± 9.4 years and 40.1 ± 11.0 years, respectively), with no differences in gender or rates of current comorbid psychiatric diagnoses between the groups.

The researchers quantified a total of 2,083 proteins, including 1,789 that were specifically quantified in all of the CSF samples, regardless of the presence or absence of FM.

Several analyses (including an ANOVA analysis with adjusted P values, a Random Forest machine learning approach that looked at relative protein abundance changes between those with ME/CFS and ME/CFS+FM, and unsupervised hierarchical clustering analyses) did not find distinguishing differences between the groups.

“The sum of these results does not support the hypothesis that ME/CFS and ME/CFS+FM are distinct entities, as currently defined,” the authors stated.

They noted that both conditions are “medically unexplained,” with core symptoms of pain, fatigue, sleep problems, and cognitive difficulty. The fact that these two syndromes coexist so often has led to the assumption that the “similarities between them outweigh the differences,” they wrote.

They pointed to some differences between the conditions, including an increase in substance P in the CSF of FM patients, but not in ME/CFS patients reported by others. There are also some immunological, physiological and genetic differences.

But if the conclusion that the two illnesses may share a similar pathophysiological basis is supported by other research that includes FM-only patients as comparators to those with ME/CFS, “this would support the notion that the two illnesses fall along a common illness spectrum and may be approached as a single entity — with implications for both diagnosis and the development of new treatment approaches,” they concluded.
 

‘Noncontributory’ Findings

Commenting on the research, Robert G. Lahita, MD, PhD, director of the Institute for Autoimmune and Rheumatic Diseases, St. Joseph Health, Wayne, New Jersey, stated that he does not regard these diseases as neurologic but rather as rheumatologic.

“Most neurologists don’t see these diseases, but as a rheumatologist, I see them every day,” said Dr. Lahita, professor of medicine at Hackensack (New Jersey) Meridian School of Medicine and a clinical professor of medicine at Rutgers New Jersey Medical School, New Brunswick. “ME/CFS isn’t as common in my practice, but we do deal with many post-COVID patients who are afflicted mostly with ME/CFS.”

He noted that an important reason for fatigue in FM is that patients generally don’t sleep, or their sleep is disrupted. This is different from the cause of fatigue in ME/CFS.

In addition, the small sample size and the lack of difference between males and females were both limitations of the current study, said Dr. Lahita, who was not involved in this research. “We know that FM disproportionately affects women — in my practice, for example, over 95% of the patients with FM are female — while ME/CFS affects both genders similarly.”

Using proteomics as a biomarker was also problematic, according to Dr. Lahita. “It would have been more valuable to investigate differences in cytokines, for example,” he suggested.

Ultimately, Dr. Lahita thinks that the study is “non-contributory to the field and, as complex as the analysis was, it does nothing to shed differentiate the two conditions or explain the syndromes themselves.”

He added that it would have been more valuable to compare ME/CFS not only to ME/CFS plus FM but also with FM without ME/CFS and to healthy controls, and perhaps to a group with an autoimmune condition, such as lupus or Hashimoto’s thyroiditis.

Dr. Schutzer acknowledged that a limitation of the current study is that his team was unable analyze the CSF of patients with only FM. He and his colleagues “combed the world’s labs” for existing CSF samples of patients with FM alone but were unable to obtain any. “We see this study as a ‘stepping stone’ and hope that future studies will include patients with FM who are willing to donate CSF samples that we can use for comparison,” he said.

The authors received support from the National Institutes of Health, National Institute of Allergy and Infectious Diseases, and National Institute of Neurological Disorders and Stroke. Dr. Schutzer, coauthors, and Dr. Lahita reported no relevant financial relationships.

TOPLINE:

Transcranial alternating current stimulation (tACS), a noninvasive technique that uses low-intensity electrical currents to modulate brain activity, is an effective intervention for treating chronic insomnia, especially in older people, results of a relatively large study suggested.

METHODOLOGY:

• The double-blind study included 124 adults with chronic insomnia (difficulty falling asleep or maintaining sleep and early morning awakening occurring at least three times a week over 3 or more months), mean age about 51 years, from two centers in China who were randomized to receive either tACS (active group) or sham tACS (control group).
• Patients underwent 20 40-minute sessions over 4 weeks; the tACS intervention involved positioning three electrodes on the scalp and applying a current of 15 mA at a frequency of 77.5 Hz, whereas the control group received no stimulation.
• Primary outcome measures included total score on the Chinese version of the self-report Pittsburgh Sleep Quality Index (PSQI), sleep onset latency, total sleep time (TST), sleep efficiency, sleep quality, and daily disturbances (such as fatigue and attention deficits).
• Secondary outcomes included Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Clinical Global Impression scale (including Clinical Global Impression Severity of Illness [CGI-SI], Clinical Global Impression Global Improvement [CGI-GI], and Clinical Global Impression Efficacy Index [CGI-EI]).
• As rates of chronic insomnia increase with age, researchers explored the influence of age on treatment benefits by dividing participants into two age groups (< 50 years and ≥ 50 years).

TAKEAWAY:

• Among the 120 participants who completed the trial, tACS resulted in a statistically significant decrease in insomnia severity compared with the control group (estimated advantage [number of points on PSQI scale], 2.61; 95% CI, 1.47-3.75; P < .001).
• There were also statistically significant estimated advantages of tACS for TST (−0.65; 95% CI, −1.06 to −0.24; P = .002), sleep efficiency (1.05; 95% CI, 0.48-1.62; P < .001), sleep quality (0.82; 95% CI, 0.29-1.34; P = .003), and daily disturbances (0.91; 95% CI, 0.58-1.25; P < .001).
• tACS exhibited significant effects on CGI-SI (0.84; 95% CI, 0.38-1.30; P < .001), CGI-GI (0.74; 95% CI, 0.42-1.06; P < .001), and CGI-EI (−0.71; 95% CI, −1.02 to −0.39; P < .001) but not on total scores of HAMD and HAMA, possibly because of the relatively low baseline levels of depression and anxiety among study subjects, said the authors.
• In the older, but not younger, group, tACS treatment had a significant benefit in sleep quality, sleep efficiency, PSQI total score, CGI-SI, CGI-GI, and CGI-EI.

IN PRACTICE:

“These significant findings contribute substantially to promoting evidence-based practices and facilitating the development of innovative treatment strategies for chronic insomnia,” the investigators wrote.

SOURCE:

The study was conducted by Xiaolin Zhu, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing, China, and colleagues. It was published online in the Journal of Psychiatric Research.

LIMITATIONS:

The follow-up period was limited to 8 weeks, so longer follow-up studies are needed to explore the sustained effects of tACS on chronic insomnia. Severity of chronic insomnia was limited by using the self-report PSQI, and not objective measures of insomnia such as polysomnography and wrist actigraphy. The age of study subjects ranged from 22 to only 65 years.

DISCLOSURES:

The study was supported by the Beijing Municipal Science and Technology Commission. The authors had no relevant conflicts of interest.

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

TOPLINE:

Transcranial alternating current stimulation (tACS), a noninvasive technique that uses low-intensity electrical currents to modulate brain activity, is an effective intervention for treating chronic insomnia, especially in older people, results of a relatively large study suggested.

METHODOLOGY:

• The double-blind study included 124 adults with chronic insomnia (difficulty falling asleep or maintaining sleep and early morning awakening occurring at least three times a week over 3 or more months), mean age about 51 years, from two centers in China who were randomized to receive either tACS (active group) or sham tACS (control group).
• Patients underwent 20 40-minute sessions over 4 weeks; the tACS intervention involved positioning three electrodes on the scalp and applying a current of 15 mA at a frequency of 77.5 Hz, whereas the control group received no stimulation.
• Primary outcome measures included total score on the Chinese version of the self-report Pittsburgh Sleep Quality Index (PSQI), sleep onset latency, total sleep time (TST), sleep efficiency, sleep quality, and daily disturbances (such as fatigue and attention deficits).
• Secondary outcomes included Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Clinical Global Impression scale (including Clinical Global Impression Severity of Illness [CGI-SI], Clinical Global Impression Global Improvement [CGI-GI], and Clinical Global Impression Efficacy Index [CGI-EI]).
• As rates of chronic insomnia increase with age, researchers explored the influence of age on treatment benefits by dividing participants into two age groups (< 50 years and ≥ 50 years).

TAKEAWAY:

• Among the 120 participants who completed the trial, tACS resulted in a statistically significant decrease in insomnia severity compared with the control group (estimated advantage [number of points on PSQI scale], 2.61; 95% CI, 1.47-3.75; P < .001).
• There were also statistically significant estimated advantages of tACS for TST (−0.65; 95% CI, −1.06 to −0.24; P = .002), sleep efficiency (1.05; 95% CI, 0.48-1.62; P < .001), sleep quality (0.82; 95% CI, 0.29-1.34; P = .003), and daily disturbances (0.91; 95% CI, 0.58-1.25; P < .001).
• tACS exhibited significant effects on CGI-SI (0.84; 95% CI, 0.38-1.30; P < .001), CGI-GI (0.74; 95% CI, 0.42-1.06; P < .001), and CGI-EI (−0.71; 95% CI, −1.02 to −0.39; P < .001) but not on total scores of HAMD and HAMA, possibly because of the relatively low baseline levels of depression and anxiety among study subjects, said the authors.
• In the older, but not younger, group, tACS treatment had a significant benefit in sleep quality, sleep efficiency, PSQI total score, CGI-SI, CGI-GI, and CGI-EI.

IN PRACTICE:

“These significant findings contribute substantially to promoting evidence-based practices and facilitating the development of innovative treatment strategies for chronic insomnia,” the investigators wrote.

SOURCE:

The study was conducted by Xiaolin Zhu, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing, China, and colleagues. It was published online in the Journal of Psychiatric Research.

LIMITATIONS:

The follow-up period was limited to 8 weeks, so longer follow-up studies are needed to explore the sustained effects of tACS on chronic insomnia. Severity of chronic insomnia was limited by using the self-report PSQI, and not objective measures of insomnia such as polysomnography and wrist actigraphy. The age of study subjects ranged from 22 to only 65 years.

DISCLOSURES:

The study was supported by the Beijing Municipal Science and Technology Commission. The authors had no relevant conflicts of interest.

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

TOPLINE:

Transcranial alternating current stimulation (tACS), a noninvasive technique that uses low-intensity electrical currents to modulate brain activity, is an effective intervention for treating chronic insomnia, especially in older people, results of a relatively large study suggested.

METHODOLOGY:

• The double-blind study included 124 adults with chronic insomnia (difficulty falling asleep or maintaining sleep and early morning awakening occurring at least three times a week over 3 or more months), mean age about 51 years, from two centers in China who were randomized to receive either tACS (active group) or sham tACS (control group).
• Patients underwent 20 40-minute sessions over 4 weeks; the tACS intervention involved positioning three electrodes on the scalp and applying a current of 15 mA at a frequency of 77.5 Hz, whereas the control group received no stimulation.
• Primary outcome measures included total score on the Chinese version of the self-report Pittsburgh Sleep Quality Index (PSQI), sleep onset latency, total sleep time (TST), sleep efficiency, sleep quality, and daily disturbances (such as fatigue and attention deficits).
• Secondary outcomes included Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Clinical Global Impression scale (including Clinical Global Impression Severity of Illness [CGI-SI], Clinical Global Impression Global Improvement [CGI-GI], and Clinical Global Impression Efficacy Index [CGI-EI]).
• As rates of chronic insomnia increase with age, researchers explored the influence of age on treatment benefits by dividing participants into two age groups (< 50 years and ≥ 50 years).

TAKEAWAY:

• Among the 120 participants who completed the trial, tACS resulted in a statistically significant decrease in insomnia severity compared with the control group (estimated advantage [number of points on PSQI scale], 2.61; 95% CI, 1.47-3.75; P < .001).
• There were also statistically significant estimated advantages of tACS for TST (−0.65; 95% CI, −1.06 to −0.24; P = .002), sleep efficiency (1.05; 95% CI, 0.48-1.62; P < .001), sleep quality (0.82; 95% CI, 0.29-1.34; P = .003), and daily disturbances (0.91; 95% CI, 0.58-1.25; P < .001).
• tACS exhibited significant effects on CGI-SI (0.84; 95% CI, 0.38-1.30; P < .001), CGI-GI (0.74; 95% CI, 0.42-1.06; P < .001), and CGI-EI (−0.71; 95% CI, −1.02 to −0.39; P < .001) but not on total scores of HAMD and HAMA, possibly because of the relatively low baseline levels of depression and anxiety among study subjects, said the authors.
• In the older, but not younger, group, tACS treatment had a significant benefit in sleep quality, sleep efficiency, PSQI total score, CGI-SI, CGI-GI, and CGI-EI.

IN PRACTICE:

“These significant findings contribute substantially to promoting evidence-based practices and facilitating the development of innovative treatment strategies for chronic insomnia,” the investigators wrote.

SOURCE:

The study was conducted by Xiaolin Zhu, Beijing Huilongguan Hospital, Peking University Huilongguan Clinical Medical School, Beijing, China, and colleagues. It was published online in the Journal of Psychiatric Research.

LIMITATIONS:

The follow-up period was limited to 8 weeks, so longer follow-up studies are needed to explore the sustained effects of tACS on chronic insomnia. Severity of chronic insomnia was limited by using the self-report PSQI, and not objective measures of insomnia such as polysomnography and wrist actigraphy. The age of study subjects ranged from 22 to only 65 years.

DISCLOSURES:

The study was supported by the Beijing Municipal Science and Technology Commission. The authors had no relevant conflicts of interest.

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

TOPLINE:

Severe sleep irregularity often occurs with obstructive sleep apnea (OSA), and this combination approximately doubled the odds of hypertension in middle-aged individuals.

METHODOLOGY:

• OSA has demonstrated an association with hypertension, but data on the impact of sleep irregularity on this relationship are lacking.
• The researchers used the recently developed sleep regularity index (SRI) to determine sleep patterns using a scale of 0-100 (with higher numbers indicating greater regularity) to assess relationships between OSA, sleep patterns, and hypertension in 602 adults with a mean age of 57 years.
• The study’s goal was an assessment of the associations between sleep regularity, OSA, and hypertension in a community sample of adults with normal circadian patterns.

TAKEAWAY:

• The odds of OSA were significantly greater for individuals with mildly irregular or severely irregular sleep than for regular sleepers (odds ratios, 1.97 and 2.06, respectively).
• Individuals with OSA and severely irregular sleep had the highest odds of hypertension compared with individuals with no OSA and regular sleep (OR, 2.34).
• However, participants with OSA and regular sleep or mildly irregular sleep had no significant increase in hypertension risk.

IN PRACTICE:

“Irregular sleep may be an important marker of OSA-related sleep disruption and may be an important modifiable health target,” the researchers wrote.

SOURCE:

The study was led by Kelly Sansom, a PhD candidate at the Centre for Sleep Science at the University of Western Australia, Albany. The study was published online in the journal Sleep.

LIMITATIONS:

The cross-sectional design prevented conclusions of causality, and the SRI is a nonspecific measure that may capture a range of phenotypes with one score; other limitations included the small sample sizes of sleep regularity groups and the use of actigraphy to collect sleep times.

DISCLOSURES:

The study was supported by an Australian Government Research Training Program Scholarship and the Raine Study PhD Top-up Scholarship; the Raine Study Scholarship is supported by the NHMRC, the Centre for Sleep Science, School of Anatomy, Physiology & Human Biology of the University of Western Australia, and the Lions Eye Institute. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Severe sleep irregularity often occurs with obstructive sleep apnea (OSA), and this combination approximately doubled the odds of hypertension in middle-aged individuals.

METHODOLOGY:

• OSA has demonstrated an association with hypertension, but data on the impact of sleep irregularity on this relationship are lacking.
• The researchers used the recently developed sleep regularity index (SRI) to determine sleep patterns using a scale of 0-100 (with higher numbers indicating greater regularity) to assess relationships between OSA, sleep patterns, and hypertension in 602 adults with a mean age of 57 years.
• The study’s goal was an assessment of the associations between sleep regularity, OSA, and hypertension in a community sample of adults with normal circadian patterns.

TAKEAWAY:

• The odds of OSA were significantly greater for individuals with mildly irregular or severely irregular sleep than for regular sleepers (odds ratios, 1.97 and 2.06, respectively).
• Individuals with OSA and severely irregular sleep had the highest odds of hypertension compared with individuals with no OSA and regular sleep (OR, 2.34).
• However, participants with OSA and regular sleep or mildly irregular sleep had no significant increase in hypertension risk.

IN PRACTICE:

“Irregular sleep may be an important marker of OSA-related sleep disruption and may be an important modifiable health target,” the researchers wrote.

SOURCE:

The study was led by Kelly Sansom, a PhD candidate at the Centre for Sleep Science at the University of Western Australia, Albany. The study was published online in the journal Sleep.

LIMITATIONS:

The cross-sectional design prevented conclusions of causality, and the SRI is a nonspecific measure that may capture a range of phenotypes with one score; other limitations included the small sample sizes of sleep regularity groups and the use of actigraphy to collect sleep times.

DISCLOSURES:

The study was supported by an Australian Government Research Training Program Scholarship and the Raine Study PhD Top-up Scholarship; the Raine Study Scholarship is supported by the NHMRC, the Centre for Sleep Science, School of Anatomy, Physiology & Human Biology of the University of Western Australia, and the Lions Eye Institute. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Severe sleep irregularity often occurs with obstructive sleep apnea (OSA), and this combination approximately doubled the odds of hypertension in middle-aged individuals.

METHODOLOGY:

• OSA has demonstrated an association with hypertension, but data on the impact of sleep irregularity on this relationship are lacking.
• The researchers used the recently developed sleep regularity index (SRI) to determine sleep patterns using a scale of 0-100 (with higher numbers indicating greater regularity) to assess relationships between OSA, sleep patterns, and hypertension in 602 adults with a mean age of 57 years.
• The study’s goal was an assessment of the associations between sleep regularity, OSA, and hypertension in a community sample of adults with normal circadian patterns.

TAKEAWAY:

• The odds of OSA were significantly greater for individuals with mildly irregular or severely irregular sleep than for regular sleepers (odds ratios, 1.97 and 2.06, respectively).
• Individuals with OSA and severely irregular sleep had the highest odds of hypertension compared with individuals with no OSA and regular sleep (OR, 2.34).
• However, participants with OSA and regular sleep or mildly irregular sleep had no significant increase in hypertension risk.

IN PRACTICE:

“Irregular sleep may be an important marker of OSA-related sleep disruption and may be an important modifiable health target,” the researchers wrote.

SOURCE:

The study was led by Kelly Sansom, a PhD candidate at the Centre for Sleep Science at the University of Western Australia, Albany. The study was published online in the journal Sleep.

LIMITATIONS:

The cross-sectional design prevented conclusions of causality, and the SRI is a nonspecific measure that may capture a range of phenotypes with one score; other limitations included the small sample sizes of sleep regularity groups and the use of actigraphy to collect sleep times.

DISCLOSURES:

The study was supported by an Australian Government Research Training Program Scholarship and the Raine Study PhD Top-up Scholarship; the Raine Study Scholarship is supported by the NHMRC, the Centre for Sleep Science, School of Anatomy, Physiology & Human Biology of the University of Western Australia, and the Lions Eye Institute. The researchers had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Zolpidem and behavior therapy significantly reduce daytime symptoms of insomnia such as fatigue, functional impairments, and depressive symptoms, data suggested.

In a randomized clinical trial of more than 200 patients with chronic insomnia, behavioral therapy was associated with a 4.7-point reduction in Multidimensional Fatigue Inventory (MFI) score. Zolpidem was associated with a 5.2-point reduction in this score.

“There may be some advantage to starting with behavioral intervention,” study author Charles Morin, PhD, Canada research chair in sleeping disorders at Laval University in Quebec City, told this news organization. “But by the same token, because it takes a bit more time to produce benefits, some patients quit too quickly. So, even if we want to minimize the use of medications because of potential side effects, there may be times where we need to use it.”

The results were published in JAMA Network Open.
 

‘Different Treatment Options’

There is growing awareness that sleep is a critical pillar of good health that is just as important as good nutrition and exercise, said Dr. Morin. Clinicians thus need to pay more attention to the toll of poor sleep on physical and mental health, he added.

For the current study, the investigators randomly assigned 211 adults with chronic insomnia to behavioral therapy, which included sleep restriction and stimulus control procedures, or zolpidem (5-10 mg nightly) for 6 weeks. Participants who achieved insomnia remission by that point were followed for 12 months. Participants who did not achieve remission were randomly assigned to a second-stage psychological therapy or medication therapy (zolpidem or trazodone).

The outcome measures were daytime functional outcomes such as mood disturbances, fatigue, functional impairments of insomnia, and physical and mental health. The researchers assessed these outcomes at baseline, 6 weeks, the end of second-stage therapy, and 3- and 12-month follow-up visits.

Both initial treatments were associated with significant and equivalent reductions in depressive symptoms, fatigue, and functional impairments. Mean change in the Beck Depression Inventory-II was −3.5 for patients in the behavioral therapy arm and −4.3 for patients in the zolpidem arm. Mean change in the MFI score was −4.7 among patients who received behavioral therapy and −5.2 among those who received zolpidem. Mean change in the Work and Social Adjustment Scale, which measured functional impairments, was −5.0 for the behavioral therapy arm and −5.1 for the zolpidem arm.

In addition, both treatments were associated with improvements in mental health, as measured by the Short-Form Health Survey (SF-36). Mean change in the mental health subscale of SF-36 was 3.5 points in the behavioral therapy arm and 2.5 points in the zolpidem arm.

Second-stage treatments were associated with further improvements, and these benefits were maintained throughout the 12 months of follow-up. These findings support adding a second treatment of insomnia as part of efforts to address daytime function, the authors wrote.

“If the first treatment doesn’t work, we should not stop there. There are different treatment options,” said Dr. Morin.

“Future developments of insomnia treatment strategies should take into account the daytime consequences of insomnia,” wrote the investigators. “Additional studies are needed to further investigate the potential benefits of switching treatment modalities and incorporating a therapeutic component that can address psychological and mood disturbances.”

The authors acknowledged that the study was limited by the lack of a control condition and by relatively small sample sizes for each treatment group, which may reduce the statistical power to detect more significant group differences. They also noted that only patients who did not achieve insomnia remission received second-stage therapy, but those who did achieve remission can still have residual daytime impairments (eg, fatigue and mood disturbances) that are associated with future relapse.
 

Compliance Needed

Commenting on the findings for this news organization, Jocelyn Y. Cheng, MD, vice chair of the public safety committee of the American Academy of Sleep Medicine (AASM) and a researcher at the pharmaceutical firm Eisai, said that the research was designed well and used established and practical assessment tools. Cheng did not participate in the study.

In 2020, AASM published a clinical practice guideline on chronic insomnia disorder that strongly recommended cognitive behavioral therapy (CBT). Some of the guideline’s authors, such as Dr. Morin, conducted the present study.

The current results offer reassurance about cases in which patients may prefer options other than CBT, said Cheng. Therapy and medication each appear to help reduce daytime outcomes of insomnia such as anxiety, she said.

Some patients are reluctant to try CBT, and others may not be able to find or participate in this kind of therapy because of other medical conditions such as traumatic brain injury. CBT “does require compliance and somebody willing to participate and also somebody able to participate,” said Cheng. “So, in that case, medication might be the better way to go [for the] first line.”

This study was funded by the National Institute of Mental Health. Dr. Morin reported receiving grants and personal fees from Eisai and Idorsia, grants from Lallemand Health, and royalties from Mapi Research Trust outside the submitted work. A coauthor reported receiving grants from Janssen Pharmaceuticals, Axsome Pharmaceutics, Attune, Harmony, Neurocrine Biosciences, Reveal Biosensors, the Ray and Dagmar Dolby Family Fund, and the National Institutes of Health; personal fees from Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, and Takeda; and stock options from Big Health and Neurawell outside the submitted work. Cheng reported no relevant financial relationships other than her employment by Eisai.

A version of this article appeared on Medscape.com.

Zolpidem and behavior therapy significantly reduce daytime symptoms of insomnia such as fatigue, functional impairments, and depressive symptoms, data suggested.

In a randomized clinical trial of more than 200 patients with chronic insomnia, behavioral therapy was associated with a 4.7-point reduction in Multidimensional Fatigue Inventory (MFI) score. Zolpidem was associated with a 5.2-point reduction in this score.

“There may be some advantage to starting with behavioral intervention,” study author Charles Morin, PhD, Canada research chair in sleeping disorders at Laval University in Quebec City, told this news organization. “But by the same token, because it takes a bit more time to produce benefits, some patients quit too quickly. So, even if we want to minimize the use of medications because of potential side effects, there may be times where we need to use it.”

The results were published in JAMA Network Open.
 

‘Different Treatment Options’

There is growing awareness that sleep is a critical pillar of good health that is just as important as good nutrition and exercise, said Dr. Morin. Clinicians thus need to pay more attention to the toll of poor sleep on physical and mental health, he added.

For the current study, the investigators randomly assigned 211 adults with chronic insomnia to behavioral therapy, which included sleep restriction and stimulus control procedures, or zolpidem (5-10 mg nightly) for 6 weeks. Participants who achieved insomnia remission by that point were followed for 12 months. Participants who did not achieve remission were randomly assigned to a second-stage psychological therapy or medication therapy (zolpidem or trazodone).

The outcome measures were daytime functional outcomes such as mood disturbances, fatigue, functional impairments of insomnia, and physical and mental health. The researchers assessed these outcomes at baseline, 6 weeks, the end of second-stage therapy, and 3- and 12-month follow-up visits.

Both initial treatments were associated with significant and equivalent reductions in depressive symptoms, fatigue, and functional impairments. Mean change in the Beck Depression Inventory-II was −3.5 for patients in the behavioral therapy arm and −4.3 for patients in the zolpidem arm. Mean change in the MFI score was −4.7 among patients who received behavioral therapy and −5.2 among those who received zolpidem. Mean change in the Work and Social Adjustment Scale, which measured functional impairments, was −5.0 for the behavioral therapy arm and −5.1 for the zolpidem arm.

In addition, both treatments were associated with improvements in mental health, as measured by the Short-Form Health Survey (SF-36). Mean change in the mental health subscale of SF-36 was 3.5 points in the behavioral therapy arm and 2.5 points in the zolpidem arm.

Second-stage treatments were associated with further improvements, and these benefits were maintained throughout the 12 months of follow-up. These findings support adding a second treatment of insomnia as part of efforts to address daytime function, the authors wrote.

“If the first treatment doesn’t work, we should not stop there. There are different treatment options,” said Dr. Morin.

“Future developments of insomnia treatment strategies should take into account the daytime consequences of insomnia,” wrote the investigators. “Additional studies are needed to further investigate the potential benefits of switching treatment modalities and incorporating a therapeutic component that can address psychological and mood disturbances.”

The authors acknowledged that the study was limited by the lack of a control condition and by relatively small sample sizes for each treatment group, which may reduce the statistical power to detect more significant group differences. They also noted that only patients who did not achieve insomnia remission received second-stage therapy, but those who did achieve remission can still have residual daytime impairments (eg, fatigue and mood disturbances) that are associated with future relapse.
 

Compliance Needed

Commenting on the findings for this news organization, Jocelyn Y. Cheng, MD, vice chair of the public safety committee of the American Academy of Sleep Medicine (AASM) and a researcher at the pharmaceutical firm Eisai, said that the research was designed well and used established and practical assessment tools. Cheng did not participate in the study.

In 2020, AASM published a clinical practice guideline on chronic insomnia disorder that strongly recommended cognitive behavioral therapy (CBT). Some of the guideline’s authors, such as Dr. Morin, conducted the present study.

The current results offer reassurance about cases in which patients may prefer options other than CBT, said Cheng. Therapy and medication each appear to help reduce daytime outcomes of insomnia such as anxiety, she said.

Some patients are reluctant to try CBT, and others may not be able to find or participate in this kind of therapy because of other medical conditions such as traumatic brain injury. CBT “does require compliance and somebody willing to participate and also somebody able to participate,” said Cheng. “So, in that case, medication might be the better way to go [for the] first line.”

This study was funded by the National Institute of Mental Health. Dr. Morin reported receiving grants and personal fees from Eisai and Idorsia, grants from Lallemand Health, and royalties from Mapi Research Trust outside the submitted work. A coauthor reported receiving grants from Janssen Pharmaceuticals, Axsome Pharmaceutics, Attune, Harmony, Neurocrine Biosciences, Reveal Biosensors, the Ray and Dagmar Dolby Family Fund, and the National Institutes of Health; personal fees from Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, and Takeda; and stock options from Big Health and Neurawell outside the submitted work. Cheng reported no relevant financial relationships other than her employment by Eisai.

A version of this article appeared on Medscape.com.

Zolpidem and behavior therapy significantly reduce daytime symptoms of insomnia such as fatigue, functional impairments, and depressive symptoms, data suggested.

In a randomized clinical trial of more than 200 patients with chronic insomnia, behavioral therapy was associated with a 4.7-point reduction in Multidimensional Fatigue Inventory (MFI) score. Zolpidem was associated with a 5.2-point reduction in this score.

“There may be some advantage to starting with behavioral intervention,” study author Charles Morin, PhD, Canada research chair in sleeping disorders at Laval University in Quebec City, told this news organization. “But by the same token, because it takes a bit more time to produce benefits, some patients quit too quickly. So, even if we want to minimize the use of medications because of potential side effects, there may be times where we need to use it.”

The results were published in JAMA Network Open.
 

‘Different Treatment Options’

There is growing awareness that sleep is a critical pillar of good health that is just as important as good nutrition and exercise, said Dr. Morin. Clinicians thus need to pay more attention to the toll of poor sleep on physical and mental health, he added.

For the current study, the investigators randomly assigned 211 adults with chronic insomnia to behavioral therapy, which included sleep restriction and stimulus control procedures, or zolpidem (5-10 mg nightly) for 6 weeks. Participants who achieved insomnia remission by that point were followed for 12 months. Participants who did not achieve remission were randomly assigned to a second-stage psychological therapy or medication therapy (zolpidem or trazodone).

The outcome measures were daytime functional outcomes such as mood disturbances, fatigue, functional impairments of insomnia, and physical and mental health. The researchers assessed these outcomes at baseline, 6 weeks, the end of second-stage therapy, and 3- and 12-month follow-up visits.

Both initial treatments were associated with significant and equivalent reductions in depressive symptoms, fatigue, and functional impairments. Mean change in the Beck Depression Inventory-II was −3.5 for patients in the behavioral therapy arm and −4.3 for patients in the zolpidem arm. Mean change in the MFI score was −4.7 among patients who received behavioral therapy and −5.2 among those who received zolpidem. Mean change in the Work and Social Adjustment Scale, which measured functional impairments, was −5.0 for the behavioral therapy arm and −5.1 for the zolpidem arm.

In addition, both treatments were associated with improvements in mental health, as measured by the Short-Form Health Survey (SF-36). Mean change in the mental health subscale of SF-36 was 3.5 points in the behavioral therapy arm and 2.5 points in the zolpidem arm.

Second-stage treatments were associated with further improvements, and these benefits were maintained throughout the 12 months of follow-up. These findings support adding a second treatment of insomnia as part of efforts to address daytime function, the authors wrote.

“If the first treatment doesn’t work, we should not stop there. There are different treatment options,” said Dr. Morin.

“Future developments of insomnia treatment strategies should take into account the daytime consequences of insomnia,” wrote the investigators. “Additional studies are needed to further investigate the potential benefits of switching treatment modalities and incorporating a therapeutic component that can address psychological and mood disturbances.”

The authors acknowledged that the study was limited by the lack of a control condition and by relatively small sample sizes for each treatment group, which may reduce the statistical power to detect more significant group differences. They also noted that only patients who did not achieve insomnia remission received second-stage therapy, but those who did achieve remission can still have residual daytime impairments (eg, fatigue and mood disturbances) that are associated with future relapse.
 

Compliance Needed

Commenting on the findings for this news organization, Jocelyn Y. Cheng, MD, vice chair of the public safety committee of the American Academy of Sleep Medicine (AASM) and a researcher at the pharmaceutical firm Eisai, said that the research was designed well and used established and practical assessment tools. Cheng did not participate in the study.

In 2020, AASM published a clinical practice guideline on chronic insomnia disorder that strongly recommended cognitive behavioral therapy (CBT). Some of the guideline’s authors, such as Dr. Morin, conducted the present study.

The current results offer reassurance about cases in which patients may prefer options other than CBT, said Cheng. Therapy and medication each appear to help reduce daytime outcomes of insomnia such as anxiety, she said.

Some patients are reluctant to try CBT, and others may not be able to find or participate in this kind of therapy because of other medical conditions such as traumatic brain injury. CBT “does require compliance and somebody willing to participate and also somebody able to participate,” said Cheng. “So, in that case, medication might be the better way to go [for the] first line.”

This study was funded by the National Institute of Mental Health. Dr. Morin reported receiving grants and personal fees from Eisai and Idorsia, grants from Lallemand Health, and royalties from Mapi Research Trust outside the submitted work. A coauthor reported receiving grants from Janssen Pharmaceuticals, Axsome Pharmaceutics, Attune, Harmony, Neurocrine Biosciences, Reveal Biosensors, the Ray and Dagmar Dolby Family Fund, and the National Institutes of Health; personal fees from Axsome Therapeutics, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Millenium Pharmaceuticals, Merck, Neurocrine Biosciences, Neurawell, Pernix, Otsuka Pharmaceuticals, Sage, and Takeda; and stock options from Big Health and Neurawell outside the submitted work. Cheng reported no relevant financial relationships other than her employment by Eisai.

A version of this article appeared on Medscape.com.

TOPLINE:

The time arrived at peak blood pressure (BP) velocity (TAPV) was significantly earlier in children with moderate to severe (MS) obstructive sleep apnea (OSA) than in controls.

METHODOLOGY:

• The researchers compared 24-hour circadian BP in children with OSA and controls to examine the impact of OSA on circadian BP.
• The study population included 219 children aged 5-14 years: 52 with mild OSA, 50 with MS OSA, and 117 controls.
• Participants underwent 24-hour BP monitoring and actigraphy; models included the times of BP peaks and TAPV.

TAKEAWAY:

• Children with MS OSA had a TAPV for diastolic BP in the morning, an average of 51 minutes earlier than controls (P < .001).
• Evening TAPV was significantly earlier in the children with MS OSA than in controls for both systolic BP (SBP) and diastolic BP (DBP) (95 min, P < .001 and 28 min, P = .028, respectively).
• Midday SBP and DBP velocity nadirs were significantly earlier in the children with MS OSA than in controls (57 min, P < .001 and 38 min, P < .01, respectively).
• Overall, children with MS OSA reached most BP values significantly earlier than controls, and both SBP and DBP were significantly elevated in the MS OSA group compared with the control group.

IN PRACTICE:

“The findings provide an essential puzzle piece in our understanding of the cardiovascular effects of OSA in children,” wrote the authors of an accompanying editorial.

SOURCE:

The lead author of the study was Md Tareq Ferdous Khan, MD, of the University of Cincinnati, Cincinnati, Ohio; the authors of the accompanying editorial were Kate Ching-Ching Chan, MD, and Albert Martin Li, MD, of the Chinese University of Hong Kong, China. The study was published online in the journal Sleep on December 13, 2023, along with the accompanying editorial.

LIMITATIONS:

More research is needed to investigate the potential mechanisms of action, optimize methodology, and investigate circadian biology via actigraphy and biomarkers, the authors of an accompanying editorial wrote.

DISCLOSURES:

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The time arrived at peak blood pressure (BP) velocity (TAPV) was significantly earlier in children with moderate to severe (MS) obstructive sleep apnea (OSA) than in controls.

METHODOLOGY:

• The researchers compared 24-hour circadian BP in children with OSA and controls to examine the impact of OSA on circadian BP.
• The study population included 219 children aged 5-14 years: 52 with mild OSA, 50 with MS OSA, and 117 controls.
• Participants underwent 24-hour BP monitoring and actigraphy; models included the times of BP peaks and TAPV.

TAKEAWAY:

• Children with MS OSA had a TAPV for diastolic BP in the morning, an average of 51 minutes earlier than controls (P < .001).
• Evening TAPV was significantly earlier in the children with MS OSA than in controls for both systolic BP (SBP) and diastolic BP (DBP) (95 min, P < .001 and 28 min, P = .028, respectively).
• Midday SBP and DBP velocity nadirs were significantly earlier in the children with MS OSA than in controls (57 min, P < .001 and 38 min, P < .01, respectively).
• Overall, children with MS OSA reached most BP values significantly earlier than controls, and both SBP and DBP were significantly elevated in the MS OSA group compared with the control group.

IN PRACTICE:

“The findings provide an essential puzzle piece in our understanding of the cardiovascular effects of OSA in children,” wrote the authors of an accompanying editorial.

SOURCE:

The lead author of the study was Md Tareq Ferdous Khan, MD, of the University of Cincinnati, Cincinnati, Ohio; the authors of the accompanying editorial were Kate Ching-Ching Chan, MD, and Albert Martin Li, MD, of the Chinese University of Hong Kong, China. The study was published online in the journal Sleep on December 13, 2023, along with the accompanying editorial.

LIMITATIONS:

More research is needed to investigate the potential mechanisms of action, optimize methodology, and investigate circadian biology via actigraphy and biomarkers, the authors of an accompanying editorial wrote.

DISCLOSURES:

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The time arrived at peak blood pressure (BP) velocity (TAPV) was significantly earlier in children with moderate to severe (MS) obstructive sleep apnea (OSA) than in controls.

METHODOLOGY:

• The researchers compared 24-hour circadian BP in children with OSA and controls to examine the impact of OSA on circadian BP.
• The study population included 219 children aged 5-14 years: 52 with mild OSA, 50 with MS OSA, and 117 controls.
• Participants underwent 24-hour BP monitoring and actigraphy; models included the times of BP peaks and TAPV.

TAKEAWAY:

• Children with MS OSA had a TAPV for diastolic BP in the morning, an average of 51 minutes earlier than controls (P < .001).
• Evening TAPV was significantly earlier in the children with MS OSA than in controls for both systolic BP (SBP) and diastolic BP (DBP) (95 min, P < .001 and 28 min, P = .028, respectively).
• Midday SBP and DBP velocity nadirs were significantly earlier in the children with MS OSA than in controls (57 min, P < .001 and 38 min, P < .01, respectively).
• Overall, children with MS OSA reached most BP values significantly earlier than controls, and both SBP and DBP were significantly elevated in the MS OSA group compared with the control group.

IN PRACTICE:

“The findings provide an essential puzzle piece in our understanding of the cardiovascular effects of OSA in children,” wrote the authors of an accompanying editorial.

SOURCE:

The lead author of the study was Md Tareq Ferdous Khan, MD, of the University of Cincinnati, Cincinnati, Ohio; the authors of the accompanying editorial were Kate Ching-Ching Chan, MD, and Albert Martin Li, MD, of the Chinese University of Hong Kong, China. The study was published online in the journal Sleep on December 13, 2023, along with the accompanying editorial.

LIMITATIONS:

More research is needed to investigate the potential mechanisms of action, optimize methodology, and investigate circadian biology via actigraphy and biomarkers, the authors of an accompanying editorial wrote.

DISCLOSURES:

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

Continuous positive airway pressure (CPAP) is first-line therapy for sleep-related breathing disorders (SRBDs). Obstructive sleep apnea (OSA) is the major player in the SRBDs space, with a prevalence approaching 100% in adult men using current diagnostic criteria. Patients with OSA and comorbid cardiovascular disease (CVD) are diagnosed with OSA syndrome, and CPAP is prescribed. Primary care physicians and cardiologists are quick to refer patients with CVD to sleep docs to see whether CPAP can improve CVD-related outcomes.

What the Studies Show

There’s a problem though. CPAP doesn’t seem to improve CVD-related outcomes. In some cases, it’s even harmful. Let’s do a quick review. In 2005, the CANPAP study found CPAP didn’t improve a composite CVD outcome that included mortality. A post hoc analysis found that it actually increased mortality if central apneas weren’t eliminated. The post hoc analysis also found benefit when central apneas were eliminated, but for all-comers, CPAP didn’t improve outcomes. Strike one.

Enter adaptive servo-ventilation (ASV). If CANPAP showed that success depended on eliminating central apneas, why not use ASV for all patients with CVD and central apneas or Cheyne-Stokes respirations? ASV eliminates central apneas and Cheyne-Stokes. Well, that didn’t work either. The randomized, controlled SERVE-HF trial, published in 2015, showed that ASV increases all-cause and CVD-specific mortality. Oops. That’s two trials showing that CPAP and ASV can increase mortality in patients with heart failure. Strike two.

Alright. But that’s heart failure. What about hypertension or coronary artery disease (CAD)? Shouldn’t such patients be treated with CPAP to reduce CVD risk? After all, there’s all those surrogate outcomes data for CPAP — it improves vascular tone and lowers catecholamines and all that stuff. Doesn’t it lower blood pressure too? Surely CPAP benefits patients with CVD who don’t have heart failure, right?

Not really. The RICCADSA study, published in 2016, found that CPAP didn’t reduce a composite of CVD outcomes in patients with newly revascularized CAD. The SAVE trial published the same year had a similar design with similar results. CPAP did not improve CVD-related outcomes. Most recently, the ISAACC study was negative. That’s three negative randomized controlled trials in less than 5 years showing CPAP doesn’t affect CVD-related outcomes in high-risk populations with known disease. Strike three?

CPAP provides no benefit for CVD and possible harm when treating heart failure. Surely CPAP is useful for patients with hypertension. Let’s see. The American Academy of Sleep Medicine (AASM) conducted meta-analyses for the guideline it produced recommending CPAP for patients with comorbid hypertension. They note that 24-hour blood pressure measurements are best correlated with outcomes. CPAP did lead to significant 24-hour blood pressure reduction, but guess how large it was? For systolic blood pressure, it was 1.5 mm Hg; for diastolic pressure, it was 1.6 mm Hg. That’s it.

How did the AASM summarize and interpret the above data in their 2019 guidelines for prescribing CPAP? Although covered in their detailed review, both heart failure and CVD are left out of their primary recommendations . They do provide a conditional recommendation for prescribing CPAP to patients with comorbid hypertension that states, “The majority of well-informed patients would choose the intervention over no treatment.” Really? If you were told that CPAP provides less reduction in blood pressure than dietary changes and/or medications, would you choose to wear it or take a pill once a day? Remember, you have to take the pill anyway to get your blood pressure to target unless your pressure is only 1.5-1.6 mm Hg above normal. Where does one find patients who are anxious to wear a mask to bed for minimal benefit and a 20% copay? I’ve yet to meet one.

As always, the pressure pushers are undeterred by inconvenient evidence. A secondary analysis of adherent patients in RICCADSA resorts to the “bait and switch” that’s propped up CPAP enthusiasts for decades: Compare adherent patients versus those who are not (or those who refuse treatment) to prove benefit. The flaws to this approach are obvious. First, performing a post hoc analysis that reintroduces all of the confounding that plagues existing CPAP data negates the benefits of randomization, fancy statistics notwithstanding. Second, it belies the reality that in well-controlled, well-conducted randomized trials where patients get far more support than those in the community (and sometimes are preselected for adherence), a majority simply won’t use CPAP . Excluding the nonadherent or comparing them with the adherent is the epitome of selection bias.

The editorial accompanying the ISAACC study is a tour de force in CPAP apologies. The apnea-hypopnea index (AHI) isn’t the right metric — this one’s invoked often. Never mind that the very premise that OSA causes CVD is from observational data based on the AHI. If you abandon the AHI, don’t you lose your justification for prospective trials targeting CVD with CPAP?

Even better, in an argument fit for a Twitter ban, the author suggests that patients in ISAACC, SAVE, and RICCADSA couldn’t benefit because they already have CVD. The very concept, refuted by decades of secondary prevention research in cardiology, implies that CPAP should be used for primary prevention. Only a sleep researcher could spin a negative study into an expansion of CPAP indications. Others in the AASM have made similar proposals.

Final Thoughts

The sleep field lacks unblinded realists capable of choosing wisely. A little therapeutic underconfidence is warranted. Diseases and therapies will always have champions. Prudence and restraint? Not so much. The AASM could summarize the CPAP literature in a single recommendation: “If your patient is sleepy, CPAP might help them feel better if their disease is moderate or severe.” All other indications are soft.

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

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary/sleep and critical care medicine physician at MedStar Washington Hospital Center in Washington, DC. He covers a  wide range of topics in pulmonary, critical care, and sleep medicine .

The smartphone and smartwatch have spun off multiple apps and platforms for remotely monitoring a host of disease states, including pulmonary diseases and sleep disorders, but, as with any emergent technology, pitfalls come along with the promise and potential.

Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.

American College of Chest Physicians

“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.

“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”

Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).

Targeting Challenges With Polysomnography

All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.

U.S. Army Medical Research and Development Command

“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.

“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”

Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.

“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”

However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.

The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.

And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.

The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.

“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.

These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”

 

Early Study of Ingestible Capsule

To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.

The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.

Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.

In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.

Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.

Celero Systems

The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of  monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”

The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.

“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.

This platform could also collect multinight data for sleep studies, he added.

“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”

 
 

AI-Aided Stethoscope

The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.

The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.

The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.

“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”

Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.

The smartphone and smartwatch have spun off multiple apps and platforms for remotely monitoring a host of disease states, including pulmonary diseases and sleep disorders, but, as with any emergent technology, pitfalls come along with the promise and potential.

Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.

American College of Chest Physicians

“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.

“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”

Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).

Targeting Challenges With Polysomnography

All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.

U.S. Army Medical Research and Development Command

“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.

“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”

Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.

“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”

However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.

The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.

And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.

The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.

“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.

These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”

 

Early Study of Ingestible Capsule

To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.

The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.

Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.

In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.

Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.

Celero Systems

The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of  monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”

The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.

“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.

This platform could also collect multinight data for sleep studies, he added.

“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”

 
 

AI-Aided Stethoscope

The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.

The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.

The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.

“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”

Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.

The smartphone and smartwatch have spun off multiple apps and platforms for remotely monitoring a host of disease states, including pulmonary diseases and sleep disorders, but, as with any emergent technology, pitfalls come along with the promise and potential.

Meanwhile, technology to remotely monitor respiratory diseases is advancing into other modalities. In recent months, researchers have reported on an artificial intelligence–aided home stethoscope to monitor asthma exacerbations and an ingestible electronic capsule, which has shown some facility for continuous, remote monitoring of sleep apnea and opioid induced respiratory depression.

American College of Chest Physicians

“Smartphones and wearable technology in health care are here to stay,” Mariam Louis, MD, pulmonologist and sleep medicine physician at the University of Florida Health and chair of the nonrespiratory sleep section of the Sleep Medicine Network with the American College of Chest Physicians, said in an interview.

“It is an exciting field, as it encourages patients to be actively involved in their medical care and can potentially offer more real-time feedback regarding the patient’s medical conditions,” she said. “There are currently many apps that are being used to monitor sleep and other diseases. However, the technology is still rudimentary, and much more research is needed to see if these apps are accurate and dependable.”

Studies in the past few months have reported on the accuracy of 18 wearable sleep-tracker devices, finding they overestimated sleep duration by 19 minutes on average (Sleep. 2023 Nov 8. doi: 10.1093/sleep/zsad288). Researchers in the United States also recently reported on the first human trial of an ingestible pill for monitoring sleep apnea that sends data to a receiving device up to six feet away (Device. 2023 Nov 17. doi: 10.1016/j.device.2023.100125), and a group in Poland reported than an AI-aided home stethoscope provided reliable information on asthma exacerbations in 149 patients (Ann Fam Med. 2023;21:517-25).

Targeting Challenges With Polysomnography

All of these technologies aim to overcome challenges with traditional devices, such as polysomnography (PSG) for evaluating sleep. Jaques Reifman, PhD, a senior research scientist at the U.S. Army Medical Research and Development Command in Fort Detrick, Maryland, led the study of 18 wearable sleep trackers. “Both polysomnography and sleep tracking devices in a sense are attempting to reach the same goal: they’re trying to estimate certain sleep parameters,” Dr. Reifman said in an interview.

U.S. Army Medical Research and Development Command

“But they use very different signals,” he added, noting that PSG uses electroencephalography (EEG) to measure electrical signals in the skull whereas most sleep trackers used an accelerometer to measure body movement. “As your wrist moves around, it determines if you are moving or not,” Dr. Reifman said.

“Each of them have their plusses and minuses,” he added. PSG, while it’s considered the gold standard for measuring sleep, isn’t a consumer product. “It generally requires a very sophisticated data acquisition system; they are laden with motion artifacts and you have to have software to remove them before you analyze the data,” Dr. Reifman said. “They generally require an expert to interpret the results, although lately there are a few AI-based algorithms that you can provide the EEG signals to and it does score those stages for you”

Sleep trackers, on the other hand, are consumer products. “They can be used outside the lab, and you can use them to record for long periods of time, which is not really possible with PSG,” Dr. Reifman said. “They are low cost, they are easy to use, small size, and folks have developed algorithms that can directly tell the consumer you slept seven hours last night.

“In that sense, they’re comfortable to use as opposed to using an almost-like shower cap with the EEG and face sensors as part of the PSG montage.”

However, what sleep trackers offer in convenience, they lack in accuracy. “There are things they just cannot do based on the limitations of the signals that they use,” Dr. Reifman said.

The study was actually a meta-analysis of 14 different studies that evaluated 18 different sleep-tracking devices in 364 patients. The meta-analysis found wide variability in accuracy between devices; for example, a 75-minute overestimation of sleep with one device and a one-minute overestimation with another.

And different studies reported variations with the same tracker or different models of a tracker. The Fitbit Charge 2, for example, was found to underestimate sleep by 12 minutes in one study and overestimate sleep by 9 minutes in another, while the Fitbit HR Charge was found to overestimate sleep by 52 minutes in a third study.

The meta-analysis found while sleep trackers have high sensitivity (>90%), they had a relatively low specificity (<50%), Dr. Reifman noted.

“Because they are mainly based on the acceleration of your wrist, if you are laying down in bed and motionless after a few minutes the device is going to think you’re asleep when in reality you’re just motionless, daydreaming or trying to go to sleep but not sleeping, so the specificity to sleep is not that high,” he said.

These types of devices still have obstacles to overcome before they’re more widely used, Dr. Louis said. “All of these technologies are proprietary,” she said. “As such, little is known about the algorithms used to come up with the diagnosis or other conclusions. In addition, the majority of the data cannot be analyzed independently by the providers, limiting some of the usage of these devices for now.”

 

Early Study of Ingestible Capsule

To overcome some of those challenges with collecting data from wearables, researchers from the Massachusetts Institute of Technology and West Virginia University have worked with Celero Systems to develop a pill-sized capsule the patient swallows and which then collects vitals data from inside the gastrointestinal tract. The first in-human study evaluated the device, called the vitals-monitoring (VM) pill, in 10 patients. The study reported the data captured by the pill aligned with that gathered with standard sleep metrics and that it could detect sleep apnea episodes.

The study described the pill as a wireless device that uses a custom configuration of four off-the shelf integrated circuits — a microcontroller, accelerometer, memory component and radio signal — and electronic sensors for ballistic measurements from within the GI tract. The accelerometer measures movement of the abdomen during breathing.

Ingestible devices have actually been around for a couple of decades. The most common, the PillCam, is mostly used by gastroenterologists to capture images of the small intestine.

In the VM pill study, 3 of the 10 human volunteers had a diagnosis of either central or obstructive sleep apnea and wore a continuous positive airway pressure device during the study. The patients also had PSG. The study found that the heart rate accuracy of the VM pill was within 2.5 beats per minute of the PSG measure. The study found no significant difference in the ability of the VM pill to accurately measure respiratory rate with or without CPAP.

Since study completion, the device has been evaluated in another 10 patients, Ben Pless, CEO of Celero Systems, the company developing the VM pill and a coauthor of the study, said in an interview. All patients passed the capsule without any adverse events, he said.

Celero Systems

The capsule carries the advantages of an implantable device without the surgery, Mr. Pless said. “In addition to the product being inside body, it is very good at measuring core temperature and, of course, there are diurnal variations in core temperature,” he said. “Even though this was not in the paper, we found the combination of  monitoring respiration and core temperature is a very powerful way to do sleep staging in a completely unobtrusive and discrete way.”

The first study evaluated the overnight use of the VM pill, but future studies will evaluate longer duration of the device, first up to a week and then extending out to a month, with the goal of collecting data through the entire duration, Mr. Pless said.

“If you want to do ongoing monitoring for events that may have a low incidence, for example COPD exacerbations or some asthma which does not occur every day and you want to do long-term monitoring, an ingestible format where you ultimately take one capsule and you’re monitored for a month in a completely unobtrusive way would be a great way to do patient monitoring,” he said.

This platform could also collect multinight data for sleep studies, he added.

“While this is an exciting technology, there is much more to diagnosing sleep apnea than just heart rate and breathing,” Dr. Louis said. “During a sleep study, we look at oxygen levels, snoring, and many other variables.”

 
 

AI-Aided Stethoscope

The AI-aided stethoscope demonstrated an ability to collect reliable information on asthma exacerbations, the study in Poland found. “The parameters provided are effective for children, especially those younger than 5 years of age,” the study authors wrote.

The study enrolled patients of various ages with asthma, using the AI-aided stethoscope to monitor asthma-related physiologic parameters at home for six months. The stethoscope recorded auscultatory sounds from standard chest point and sent them to a dedicated mobile phone application in which an AI module automatically analyzed the recordings and displayed the results. The researchers trained the AI module using more than 10,000 recordings of respiratory sounds.

The study showed that a host of parameters — wheezes, rhonchi, coarse and fine crackles, heart rate, respiratory rate and inspiration-to-expiration duration ration — measured with the AI-aided stethoscope can detect asthma exacerbations without the need for obtaining peak expiratory flow measurements. It also showed a potential to make asthma diagnosis more straightforward in younger children.

“As we learn more and refine these technologies, we will be able to offer more patient centered and precise medicine to our patients, tailored specifically to their needs,” Dr. Louis said. “AI will certainly play a part in the future.”

Dr. Louis and Dr. Reifman have no relevant relationships to disclose. Mr. Pless is CEO of Celero Systems, a privately held company in Lincoln, Mass.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Light therapy leads to significant improvement in several sleep measures and helps alleviate depression and agitation in patients with Alzheimer’s disease (AD), a meta-analysis of 15 high-quality trials shows.

METHODOLOGY:

• This meta-analysis included 15 randomized controlled trials involving 598 patients with mild to moderate AD.
• The included trials were written in English, published between 2005 and 2022, and performed in seven countries. A fixed-effects model was used for data analysis.

TAKEAWAY:

• Light therapy significantly improved sleep efficiency (mean difference [MD], −2.42; P < .00001), increased interdaily stability (MD, −0.04; P < .00001), and reduced intradaily variability (MD, −0.04; P < .00001), indicating better sleep quality.
• Light therapy reduced agitation (MD, −3.97; P < .00001), depression (MD, −2.55; P < .00001), and caregiver burden (MD, −3.57; P < .00001).
• Light therapy also had a significant advantage over usual care in reducing the severity of psychobehavioral symptoms as assessed by the Neuropsychiatric Inventory (MD, −3.07; P < .00001).
• Light therapy had no statistically significant effect on improving cognitive function as measured by the Mini-Mental State Examination.

IN PRACTICE:

“These findings, combined with its low side-effects, suggest the role of light therapy as a promising treatment for AD. Although light therapy has fewer side effects than pharmacological treatment, adverse behavioral outcomes in patients due to bright light exposure should be considered,” the authors wrote.

SOURCE:

The study by Lili Zang and colleagues from Weifang Medical University School of Nursing, Shandong Province, China, was published online on December 6, 2023, in PLOS One.

LIMITATIONS:

The types and degrees of dementia in the included studies were inconsistent, potentially affecting the outcome indicators. Some articles did not clearly describe their randomization and allocation concealment methods, indicating possible bias in these studies.

DISCLOSURES:

The study was supported by the Natural Science Foundation of Shandong Province, China. The authors declared no competing interests.

Megan Brooks has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Sleep disorders in people with epilepsy are linked to a significantly higher risk for sudden unexplained death in epilepsy (SUDEP) and all-cause mortality, new research shows.

SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.

“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.

She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.

The findings were presented at the annual meeting of the American Epilepsy Society (AES).

The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.

The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.

They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
 

SUDEP Inventory

Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.

Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).

Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).

The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.

From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
 

Powerful Study

Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.

“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.

Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.

Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.

Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.

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

ORLANDO — Sleep disorders in people with epilepsy are linked to a significantly higher risk for sudden unexplained death in epilepsy (SUDEP) and all-cause mortality, new research shows.

SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.

“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.

She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.

The findings were presented at the annual meeting of the American Epilepsy Society (AES).

The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.

The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.

They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
 

SUDEP Inventory

Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.

Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).

Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).

The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.

From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
 

Powerful Study

Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.

“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.

Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.

Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.

Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.

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

ORLANDO — Sleep disorders in people with epilepsy are linked to a significantly higher risk for sudden unexplained death in epilepsy (SUDEP) and all-cause mortality, new research shows.

SUDEP is a major concern for patients with epilepsy, said study investigator Marion Lazaj, MSc, Center for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada, but she believes that SUDEP risk assessment is overly focused on seizure control.

“We want to push the idea that this mortality risk assessment needs to be widened to include sleep factors, and not just sleep disorders but even sleep disturbances,” said Ms. Lazaj.

She also believes physicians should routinely discuss SUDEP with their patients with epilepsy. Given that the incidence of SUDEP is only about 1%, many clinicians don’t want to unduly frighten their patients, she added.

The findings were presented at the annual meeting of the American Epilepsy Society (AES).

The retrospective study included chart data from 1,506 consecutive patients diagnosed with epilepsy at a single center over 4 years. The mean age of participants was about 37 years but there was a large age range, said Ms. Lazaj.

The cohort was divided into two groups. Group 1 included 1130 patients without a comorbid sleep disorder, and Group 2 had 376 patients with a primary comorbid sleep disorder, mostly obstructive sleep apnea (OSA) but also restless leg syndrome or insomnia.

They gathered demographic information including age, sex, employment status, education, and epilepsy-related data such as epilepsy type, duration, the number of anti-seizure medications and relevant information from hospital and emergency room (ER) records.
 

SUDEP Inventory

Researchers assessed SUDEP risk using the revised SUDEP-7 risk inventory. The first four items on this inventory focus on generalized tonic clonic seizure activity and occurrence while others assess the number of antiseizure medicines, epilepsy duration, and the presence of other developmental delays.

Investigators then stratified patients into high risk (score on the SUDEP-7 of 5 or greater) and low mortality risk (score less than 5).

Results showed a significant association between a high mortality risk and having a comorbid sleep disorder (P = .033). Researchers also looked at all-cause mortality, including drownings and suicides, and found a similar significant association (P = .026). There was also an association between high risk and accidents and trauma (P = .042).

The researchers had access to overnight diagnostic polysomnography data for a smaller group of patients. Here, they found decreased sleep efficiency (P =.0098), increased spontaneous arousal index (P = .034), and prolonged sleep onset latency (P = .0000052) were all significantly associated with high SUDEP risk.

From the polysomnographic data, researchers found high SUDEP risk was significantly associated with a diagnosis of OSA (P = .034).
 

Powerful Study

Commenting on the findings, Gordon F. Buchanan, MD, PhD, Beth L. Tross epilepsy associate professor, Department of Neurology, University of Iowa Carver College of Medicine, Iowa City, said he was “very excited” by the research.

“That this study attempts to look through data in a retrospective way and see if there’s additional risk with having comorbid sleep disorders is really interesting and I think really powerful,” he said.

Sleep disorders “are potentially a really simple thing that we can screen for and test for,” he added. He also noted that additional research is needed to replicate the findings.

Dr. Buchanan acknowledged that the SUDEP-7 inventory is not a particularly good tool and said there is a need for a better means of assessment that includes sleep disorders and other factors like sleep states and circadian rhythm, which he said affect SUDEP risk.

Ms. Lazaj and Dr. Buchanan report no relevant financial relationships.

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