CHEST Physician

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.

Proper care of teeth and gums may offer benefits beyond oral health, including improving brain health, new research suggests.

In a large observational study of middle-aged adults without stroke or dementia, poor oral health was strongly associated with multiple neuroimaging markers of white matter injury.

“Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health,” wrote the authors, led by Cyprien A. Rivier, MD, MS, with the Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.

The study was published online on December 20, 2023, in Neurology.

Research data came from 40,175 adults (mean age, 55 years; 53% women) with no history of stroke or dementia who enrolled in the UK Biobank from 2006 to 2010 and had brain MRI between 2014 and 2016.

Altogether, 5470 (14%) participants had poor oral health, defined as the presence of dentures or loose teeth. Those with poor (vs optimal) oral health were older, more likely to be male, and had higher prevalence of hypertension, hypercholesterolemia, diabetes, overweight/obesity, and current or past smoking history.

In a multivariable model, poor oral health was associated with a 9% increase in white matter hyperintensity (WMH) volume (P < .001), a well-established marker of clinically silent cerebrovascular disease.

Poor oral health was also associated with a 10% change in aggregate fractional anisotropy (FA) score (P < .001) and a 5% change in aggregate mean diffusivity (MD) score (P < .001), two diffusion tensor imaging metrics that accurately represent white matter disintegrity.

Genetic analyses using Mendelian randomization confirmed these associations. Individuals who were genetically prone to poor oral health had a 30% increase in WMH volume (P < .001), 43% change in aggregate FA score (P < .001), and 10% change in aggregate MD score (P < .01), the researchers reported.

These findings, they noted, add to prior epidemiologic evidence for an association between poor oral health and a higher risk for clinical outcomes related to brain health, including cognitive decline.

‘Huge Dividends’

The authors of an accompanying editorial praised the authors for looking at the consequences of poor oral health in a “new and powerful way by using as their outcome MRI-defined white matter injury, which is associated with, but antedates by many years, cognitive decline and stroke.”

“The fact that these imaging changes are seen in asymptomatic persons offers the hope that if the association is causal, interventions to improve oral health could pay huge dividends in subsequent brain health,” wrote Steven J. Kittner, MD, MPH, and Breana L. Taylor, MD, with the Department of Neurology, University of Maryland School of Medicine in Baltimore.

“The mechanisms mediating the relationship between the oral health genetic risk score and white matter injury are likely to be complex, but the authors have taken an important step forward in addressing a hypothesis of immense public health importance,” they added.

Data from the World Health Organization suggested that oral diseases, which are largely preventable, affect nearly 3.5 billion people globally, with three out of four people affected in middle-income countries.

Funding for the study was provided in part by grants from the National Institutes of Health, the American Heart Association, and the Neurocritical Care Society Research Fellowship. The authors and editorialists disclosed no relevant conflicts of interest.

Megan Brooks has disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Proper care of teeth and gums may offer benefits beyond oral health, including improving brain health, new research suggests.

In a large observational study of middle-aged adults without stroke or dementia, poor oral health was strongly associated with multiple neuroimaging markers of white matter injury.

“Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health,” wrote the authors, led by Cyprien A. Rivier, MD, MS, with the Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.

The study was published online on December 20, 2023, in Neurology.

Research data came from 40,175 adults (mean age, 55 years; 53% women) with no history of stroke or dementia who enrolled in the UK Biobank from 2006 to 2010 and had brain MRI between 2014 and 2016.

Altogether, 5470 (14%) participants had poor oral health, defined as the presence of dentures or loose teeth. Those with poor (vs optimal) oral health were older, more likely to be male, and had higher prevalence of hypertension, hypercholesterolemia, diabetes, overweight/obesity, and current or past smoking history.

In a multivariable model, poor oral health was associated with a 9% increase in white matter hyperintensity (WMH) volume (P < .001), a well-established marker of clinically silent cerebrovascular disease.

Poor oral health was also associated with a 10% change in aggregate fractional anisotropy (FA) score (P < .001) and a 5% change in aggregate mean diffusivity (MD) score (P < .001), two diffusion tensor imaging metrics that accurately represent white matter disintegrity.

Genetic analyses using Mendelian randomization confirmed these associations. Individuals who were genetically prone to poor oral health had a 30% increase in WMH volume (P < .001), 43% change in aggregate FA score (P < .001), and 10% change in aggregate MD score (P < .01), the researchers reported.

These findings, they noted, add to prior epidemiologic evidence for an association between poor oral health and a higher risk for clinical outcomes related to brain health, including cognitive decline.

‘Huge Dividends’

The authors of an accompanying editorial praised the authors for looking at the consequences of poor oral health in a “new and powerful way by using as their outcome MRI-defined white matter injury, which is associated with, but antedates by many years, cognitive decline and stroke.”

“The fact that these imaging changes are seen in asymptomatic persons offers the hope that if the association is causal, interventions to improve oral health could pay huge dividends in subsequent brain health,” wrote Steven J. Kittner, MD, MPH, and Breana L. Taylor, MD, with the Department of Neurology, University of Maryland School of Medicine in Baltimore.

“The mechanisms mediating the relationship between the oral health genetic risk score and white matter injury are likely to be complex, but the authors have taken an important step forward in addressing a hypothesis of immense public health importance,” they added.

Data from the World Health Organization suggested that oral diseases, which are largely preventable, affect nearly 3.5 billion people globally, with three out of four people affected in middle-income countries.

Funding for the study was provided in part by grants from the National Institutes of Health, the American Heart Association, and the Neurocritical Care Society Research Fellowship. The authors and editorialists disclosed no relevant conflicts of interest.

Megan Brooks has disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Proper care of teeth and gums may offer benefits beyond oral health, including improving brain health, new research suggests.

In a large observational study of middle-aged adults without stroke or dementia, poor oral health was strongly associated with multiple neuroimaging markers of white matter injury.

“Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health,” wrote the authors, led by Cyprien A. Rivier, MD, MS, with the Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.

The study was published online on December 20, 2023, in Neurology.

Research data came from 40,175 adults (mean age, 55 years; 53% women) with no history of stroke or dementia who enrolled in the UK Biobank from 2006 to 2010 and had brain MRI between 2014 and 2016.

Altogether, 5470 (14%) participants had poor oral health, defined as the presence of dentures or loose teeth. Those with poor (vs optimal) oral health were older, more likely to be male, and had higher prevalence of hypertension, hypercholesterolemia, diabetes, overweight/obesity, and current or past smoking history.

In a multivariable model, poor oral health was associated with a 9% increase in white matter hyperintensity (WMH) volume (P < .001), a well-established marker of clinically silent cerebrovascular disease.

Poor oral health was also associated with a 10% change in aggregate fractional anisotropy (FA) score (P < .001) and a 5% change in aggregate mean diffusivity (MD) score (P < .001), two diffusion tensor imaging metrics that accurately represent white matter disintegrity.

Genetic analyses using Mendelian randomization confirmed these associations. Individuals who were genetically prone to poor oral health had a 30% increase in WMH volume (P < .001), 43% change in aggregate FA score (P < .001), and 10% change in aggregate MD score (P < .01), the researchers reported.

These findings, they noted, add to prior epidemiologic evidence for an association between poor oral health and a higher risk for clinical outcomes related to brain health, including cognitive decline.

‘Huge Dividends’

The authors of an accompanying editorial praised the authors for looking at the consequences of poor oral health in a “new and powerful way by using as their outcome MRI-defined white matter injury, which is associated with, but antedates by many years, cognitive decline and stroke.”

“The fact that these imaging changes are seen in asymptomatic persons offers the hope that if the association is causal, interventions to improve oral health could pay huge dividends in subsequent brain health,” wrote Steven J. Kittner, MD, MPH, and Breana L. Taylor, MD, with the Department of Neurology, University of Maryland School of Medicine in Baltimore.

“The mechanisms mediating the relationship between the oral health genetic risk score and white matter injury are likely to be complex, but the authors have taken an important step forward in addressing a hypothesis of immense public health importance,” they added.

Data from the World Health Organization suggested that oral diseases, which are largely preventable, affect nearly 3.5 billion people globally, with three out of four people affected in middle-income countries.

Funding for the study was provided in part by grants from the National Institutes of Health, the American Heart Association, and the Neurocritical Care Society Research Fellowship. The authors and editorialists disclosed no relevant conflicts of interest.

Megan Brooks has disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

The first time I saw a patient in the hospital was in 2004, twenty years ago, when I was a third-year med student. I mean, look at that guy. The things I could tell him.

Since that time, I have spent countless hours in the hospital as a resident, a renal fellow, and finally as an attending. And I’m sure many of you in the medical community feel the same thing I do, which is that patients are much more complicated now than they used to be. I’ll listen to an intern present a new case on rounds and she’ll have an assessment and plan that encompasses a dozen individual medical problems. Sometimes I have to literally be like, “Wait, why is this patient here again?”

But until now, I had no data to convince myself that this feeling was real — that hospitalized patients are getting more and more complicated, or that they only seem more complicated because I’m getting older. Maybe I was better able to keep track of things when I was an intern rather than now as an attending, spending just a couple months of the year in the hospital. I mean, after all, if patients were getting more complicated, surely hospitals would know this and allocate more resources to patient care, right?

Right?

It’s not an illusion. At least not according to this paper, Population-Based Trends in Complexity of Hospital Inpatients, appearing in JAMA Internal Medicine, which examines about 15 years of inpatient hospital admissions in British Columbia.

I like Canada for this study for two reasons: First, their electronic health record system is province-wide, so they don’t have issues of getting data from hospital A vs hospital B. All the data are there — in this case, more than 3 million nonelective hospital admissions from British Columbia. Second, there is universal healthcare. We don’t have to worry about insurance companies changing, or the start of a new program like the Affordable Care Act. It’s just a cleaner set-up.

Of course, complexity is hard to define, and the authors here decide to look at a variety of metrics I think we can agree are tied into complexity. These include things like patient age, comorbidities, medications, frequency of hospitalization, and so on. They also looked at outcomes associated with hospitalization: Did the patient require the ICU? Did they survive? Were they readmitted?

And the tale of the tape is as clear as that British Columbian air: Over the past 15 years, your average hospitalized patient is about 3 years older, is twice as likely to have kidney disease, 70% more likely to have diabetes, is on more medications (particularly anticoagulants), and is much more likely to be admitted through the emergency room. They’ve also spent more time in the hospital in the past year.

Given the increased complexity, you might expect that the outcomes for these patients are worse than years ago, but the data do not bear that out. In fact, inpatient mortality is lower now than it was 15 years ago, although 30-day postdischarge mortality is higher. Put those together and it turns out that death rates are pretty stable: 9% of people admitted for nonelective reasons to the hospital will die within 30 days. It’s just that nowadays, we tend to discharge them before that happens.

Why are our patients getting more complex? Some of it is demographics; the population is aging, after all. Some of it relates to the increasing burden of comorbidities like diabetes and kidney disease, which are associated with the obesity epidemic. But in some ways, we’re a victim of our own success. We have the ability to keep people alive today who would not have survived 15 years ago. We have better treatments for metastatic cancer, less-invasive therapies for heart disease, better protocolized ICU care.

Given all that, does it make any sense that many of our hospitals are at skeleton-crew staffing levels? That hospitalists report taking care of more patients than they ever have before?

There’s been so much talk about burnout in the health professions lately. Maybe something people need to start acknowledging — particularly those who haven’t practiced on the front lines for a decade or two — is that the job is, quite simply, harder now. As patients become more complex, we need more resources, human and otherwise, to care for them.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A new study shows sudden cardiac deaths among collegiate athletes decreased over a recent 20-year period, but risks are still elevated among males, Black players, and basketball players, suggesting more intensive screening among these groups is needed.

METHODOLOGY:

• The study examined incidence and surrounding circumstances of sudden cardiac death (SCD) among student athletes who competed in at least one varsity sport at National Collegiate Athletic Association (NCAA) Division I, II, or III institutions in the 20 years from July 1, 2002, to June 30, 2022.
• Researchers determined causes of death and gathered demographic characteristics using multiple methods, including review of autopsy and other official documents, Internet searches, and contacts to next of kin, coaches, athletic trainers, coroners, medical examiners, scholarship foundations, and physicians involved in the case.
• SCD was defined as sudden unexpected death attributable to a cardiac cause, or a sudden death in a structurally normal heart with no other explanation for death and a history consistent with cardiac-related death that occurred within an hour of symptom onset, or an unwitnessed death occurring within 24 hours of the person being alive.
• Researchers calculated incidence rates over a typical 4-year collegiate career and reported these as athlete-years.

TAKEAWAY:

• The incidence of SCD, which accounted for 13% of the 1102 total deaths during the study period, decreased over time, with a 5-year incidence rate ratio (IRR) of 0.71 (95% CI, 0.61-0.82), while noncardiovascular deaths remained stable.
• IRR for males versus females was 3.79 (95% CI, 2.45-5.88) and for Black versus White athletes was 2.79 (95% CI, 1.98-3.94).
• Basketball and football players were at increased risk of SCD; for example, the incidence rate among Division I Black male basketball athletes was 1:1924 per 4-year athlete-years.
• The most common postmortem finding was autopsy-negative sudden unexplained death, at 19%, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (17%) and hypertrophic cardiomyopathy (13%), with no cases of death attributable to COVID-19 myocarditis.

IN PRACTICE:

Although the reason for the decrease in SCD is unknown, “our data suggest that strategies to reduce SCD among competing athletes may be having a positive effect,” wrote the authors. More intensive screening strategies among groups with high SCD incidence may be warranted, they added.

SOURCE:

The study was conducted by Bradley J. Petek, MD, Sports Cardiology Program, Knight Cardiovascular Institute, Oregon Health & Science University, Portland. It was published online November 13 in Circulation and presented at the American Heart Association scientific sessions (abstract 479).

LIMITATIONS:

Some cases of SCD may have been missed as there is no mandatory reporting system in the United States. Approaches to cardiac autopsy and reporting varied significantly. The cause of death was unknown in 16 cases, and postmortem genetic testing was available for only 3% of athletes. As the study didn’t have data on resuscitated sudden cardiac arrest or preparticipation cardiovascular screening practices and findings, definitive conclusions couldn’t be drawn regarding causal factors underlying the decreased incidence of SCD.

DISCLOSURES:

There was no outside funding source. Dr. Petek has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article appeared on Medscape.com.

TOPLINE:

A new study shows sudden cardiac deaths among collegiate athletes decreased over a recent 20-year period, but risks are still elevated among males, Black players, and basketball players, suggesting more intensive screening among these groups is needed.

METHODOLOGY:

• The study examined incidence and surrounding circumstances of sudden cardiac death (SCD) among student athletes who competed in at least one varsity sport at National Collegiate Athletic Association (NCAA) Division I, II, or III institutions in the 20 years from July 1, 2002, to June 30, 2022.
• Researchers determined causes of death and gathered demographic characteristics using multiple methods, including review of autopsy and other official documents, Internet searches, and contacts to next of kin, coaches, athletic trainers, coroners, medical examiners, scholarship foundations, and physicians involved in the case.
• SCD was defined as sudden unexpected death attributable to a cardiac cause, or a sudden death in a structurally normal heart with no other explanation for death and a history consistent with cardiac-related death that occurred within an hour of symptom onset, or an unwitnessed death occurring within 24 hours of the person being alive.
• Researchers calculated incidence rates over a typical 4-year collegiate career and reported these as athlete-years.

TAKEAWAY:

• The incidence of SCD, which accounted for 13% of the 1102 total deaths during the study period, decreased over time, with a 5-year incidence rate ratio (IRR) of 0.71 (95% CI, 0.61-0.82), while noncardiovascular deaths remained stable.
• IRR for males versus females was 3.79 (95% CI, 2.45-5.88) and for Black versus White athletes was 2.79 (95% CI, 1.98-3.94).
• Basketball and football players were at increased risk of SCD; for example, the incidence rate among Division I Black male basketball athletes was 1:1924 per 4-year athlete-years.
• The most common postmortem finding was autopsy-negative sudden unexplained death, at 19%, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (17%) and hypertrophic cardiomyopathy (13%), with no cases of death attributable to COVID-19 myocarditis.

IN PRACTICE:

Although the reason for the decrease in SCD is unknown, “our data suggest that strategies to reduce SCD among competing athletes may be having a positive effect,” wrote the authors. More intensive screening strategies among groups with high SCD incidence may be warranted, they added.

SOURCE:

The study was conducted by Bradley J. Petek, MD, Sports Cardiology Program, Knight Cardiovascular Institute, Oregon Health & Science University, Portland. It was published online November 13 in Circulation and presented at the American Heart Association scientific sessions (abstract 479).

LIMITATIONS:

Some cases of SCD may have been missed as there is no mandatory reporting system in the United States. Approaches to cardiac autopsy and reporting varied significantly. The cause of death was unknown in 16 cases, and postmortem genetic testing was available for only 3% of athletes. As the study didn’t have data on resuscitated sudden cardiac arrest or preparticipation cardiovascular screening practices and findings, definitive conclusions couldn’t be drawn regarding causal factors underlying the decreased incidence of SCD.

DISCLOSURES:

There was no outside funding source. Dr. Petek has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article appeared on Medscape.com.

TOPLINE:

A new study shows sudden cardiac deaths among collegiate athletes decreased over a recent 20-year period, but risks are still elevated among males, Black players, and basketball players, suggesting more intensive screening among these groups is needed.

METHODOLOGY:

• The study examined incidence and surrounding circumstances of sudden cardiac death (SCD) among student athletes who competed in at least one varsity sport at National Collegiate Athletic Association (NCAA) Division I, II, or III institutions in the 20 years from July 1, 2002, to June 30, 2022.
• Researchers determined causes of death and gathered demographic characteristics using multiple methods, including review of autopsy and other official documents, Internet searches, and contacts to next of kin, coaches, athletic trainers, coroners, medical examiners, scholarship foundations, and physicians involved in the case.
• SCD was defined as sudden unexpected death attributable to a cardiac cause, or a sudden death in a structurally normal heart with no other explanation for death and a history consistent with cardiac-related death that occurred within an hour of symptom onset, or an unwitnessed death occurring within 24 hours of the person being alive.
• Researchers calculated incidence rates over a typical 4-year collegiate career and reported these as athlete-years.

TAKEAWAY:

• The incidence of SCD, which accounted for 13% of the 1102 total deaths during the study period, decreased over time, with a 5-year incidence rate ratio (IRR) of 0.71 (95% CI, 0.61-0.82), while noncardiovascular deaths remained stable.
• IRR for males versus females was 3.79 (95% CI, 2.45-5.88) and for Black versus White athletes was 2.79 (95% CI, 1.98-3.94).
• Basketball and football players were at increased risk of SCD; for example, the incidence rate among Division I Black male basketball athletes was 1:1924 per 4-year athlete-years.
• The most common postmortem finding was autopsy-negative sudden unexplained death, at 19%, followed by idiopathic left ventricular hypertrophy/possible cardiomyopathy (17%) and hypertrophic cardiomyopathy (13%), with no cases of death attributable to COVID-19 myocarditis.

IN PRACTICE:

Although the reason for the decrease in SCD is unknown, “our data suggest that strategies to reduce SCD among competing athletes may be having a positive effect,” wrote the authors. More intensive screening strategies among groups with high SCD incidence may be warranted, they added.

SOURCE:

The study was conducted by Bradley J. Petek, MD, Sports Cardiology Program, Knight Cardiovascular Institute, Oregon Health & Science University, Portland. It was published online November 13 in Circulation and presented at the American Heart Association scientific sessions (abstract 479).

LIMITATIONS:

Some cases of SCD may have been missed as there is no mandatory reporting system in the United States. Approaches to cardiac autopsy and reporting varied significantly. The cause of death was unknown in 16 cases, and postmortem genetic testing was available for only 3% of athletes. As the study didn’t have data on resuscitated sudden cardiac arrest or preparticipation cardiovascular screening practices and findings, definitive conclusions couldn’t be drawn regarding causal factors underlying the decreased incidence of SCD.

DISCLOSURES:

There was no outside funding source. Dr. Petek has reported no relevant financial relationships. Disclosures for the other authors are listed with the article.

A version of this article appeared on Medscape.com.

In 2023, CHEST awarded $300,000 in clinical research and community impact grants to 15 individuals. Grant recipients are recognized for their scientifically meritorious achievements, with rigorous metrics to track their project’s progress, and have innovative, novel approaches to addressing their research topic.

CHEST grants have made a difference in patients’ lives by leading to breakthroughs in the treatment and/or management of chest diseases and patient care. This year’s grant-funded projects run the gamut of topics within chest medicine, ranging from lung cancer and COPD to tuberculosis and idiopathic pulmonary fibrosis.

Here’s a glimpse into two of this year’s grant winners and their projects.

For a full list of the 2023 grant winners, visit chestnet.org/grant-recipients.
 

Air pollution in sarcoidosis

This year, the John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis was awarded to Ali Mustafa, MD, of the Johns Hopkins Hospital in Baltimore, MD, for his project “Air Pollution in Sarcoidosis.”

Courtesy CHEST

The project’s aim is to investigate the feasibility of studying indoor and outdoor air pollution in patients with pulmonary sarcoidosis.

According to Dr. Mustafa’s application, pulmonary sarcoidosis is one of the most common interstitial lung diseases in the United States, and mortality due to sarcoidosis has risen by more than 3% in recent decades.

While the etiology of sarcoidosis remains elusive, evidence points toward a combination of genetic predisposition with external environmental triggers affecting disease onset. One small study of 16 individuals with fibrotic pulmonary sarcoidosis assessed the association between local levels of outdoor air pollutants to clinical outcomes. This study found that increased short-term exposure was associated with increased respiratory symptom severity and worse health-related quality of life.

Additionally, significant health disparities exist in sarcoidosis. Black individuals with sarcoidosis have worse pulmonary function, higher rates of multiorgan disease, and as much as a 12-fold increase in mortality compared with non-Hispanic White individuals with sarcoidosis. Socioeconomic status and Black race have also been associated with increased exposure to air pollution and closer proximity to high toxic emission facilities, suggesting higher exposure to outdoor air pollution.

Racial disparities are present and particularly important in sarcoidosis. Black individuals are more likely to have more advanced disease at diagnosis, have a six-fold increase in hospitalization, and a 12-fold increase in mortality compared with non-Hispanic White individuals with sarcoidosis. Little is known about the drivers of these disparities; however, environmental exposure has been implicated in sarcoidosis pathogenesis and incidence and may be an important contributor.

Dr. Mustafa’s preliminary work suggests disparities in exposure to air pollution among individuals with sarcoidosis may be contributing to inequities in clinical outcomes.
 

Determinants of medication non-adherence among adults with chronic obstructive pulmonary disease

The CHEST/ALA/ATS Respiratory Health Equity Research Award was given to Stephanie LaBedz, MD, of the University of Illinois Chicago. The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and CHEST.

Courtesy CHEST

Dr. LaBedz’s project, “Determinants of Medication Non-Adherence Among Adults With Chronic Obstructive Pulmonary Disease,” aims to use behavioral science theory to identify barriers and facilitators to COPD medication adherence.

Studies suggest racial minorities and individuals of low socioeconomic status (SES) are less likely to be adherent to COPD medications compared with White and high SES patients with COPD. Interventions designed to improve COPD medication adherence must address barriers to adherence experienced by these groups to avoid perpetuating disparities in adherence and downstream outcomes disparities.

For her project, Dr. LaBedz will focus on examining barriers and facilitators of COPD medication adherence, including social determinants of health and other structural barriers faced by these vulnerable populations. She will use the information gained from the qualitative study to design interventions that address the barriers to adherence faced by these groups.

Her long-term goal is to improve COPD medication adherence in vulnerable patients with COPD in order to improve the health status and reduce health disparities experienced by racial/ethnic minority and low SES patients with COPD.

In 2023, CHEST awarded $300,000 in clinical research and community impact grants to 15 individuals. Grant recipients are recognized for their scientifically meritorious achievements, with rigorous metrics to track their project’s progress, and have innovative, novel approaches to addressing their research topic.

CHEST grants have made a difference in patients’ lives by leading to breakthroughs in the treatment and/or management of chest diseases and patient care. This year’s grant-funded projects run the gamut of topics within chest medicine, ranging from lung cancer and COPD to tuberculosis and idiopathic pulmonary fibrosis.

Here’s a glimpse into two of this year’s grant winners and their projects.

For a full list of the 2023 grant winners, visit chestnet.org/grant-recipients.
 

Air pollution in sarcoidosis

This year, the John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis was awarded to Ali Mustafa, MD, of the Johns Hopkins Hospital in Baltimore, MD, for his project “Air Pollution in Sarcoidosis.”

Courtesy CHEST

The project’s aim is to investigate the feasibility of studying indoor and outdoor air pollution in patients with pulmonary sarcoidosis.

According to Dr. Mustafa’s application, pulmonary sarcoidosis is one of the most common interstitial lung diseases in the United States, and mortality due to sarcoidosis has risen by more than 3% in recent decades.

While the etiology of sarcoidosis remains elusive, evidence points toward a combination of genetic predisposition with external environmental triggers affecting disease onset. One small study of 16 individuals with fibrotic pulmonary sarcoidosis assessed the association between local levels of outdoor air pollutants to clinical outcomes. This study found that increased short-term exposure was associated with increased respiratory symptom severity and worse health-related quality of life.

Additionally, significant health disparities exist in sarcoidosis. Black individuals with sarcoidosis have worse pulmonary function, higher rates of multiorgan disease, and as much as a 12-fold increase in mortality compared with non-Hispanic White individuals with sarcoidosis. Socioeconomic status and Black race have also been associated with increased exposure to air pollution and closer proximity to high toxic emission facilities, suggesting higher exposure to outdoor air pollution.

Racial disparities are present and particularly important in sarcoidosis. Black individuals are more likely to have more advanced disease at diagnosis, have a six-fold increase in hospitalization, and a 12-fold increase in mortality compared with non-Hispanic White individuals with sarcoidosis. Little is known about the drivers of these disparities; however, environmental exposure has been implicated in sarcoidosis pathogenesis and incidence and may be an important contributor.

Dr. Mustafa’s preliminary work suggests disparities in exposure to air pollution among individuals with sarcoidosis may be contributing to inequities in clinical outcomes.
 

Determinants of medication non-adherence among adults with chronic obstructive pulmonary disease

The CHEST/ALA/ATS Respiratory Health Equity Research Award was given to Stephanie LaBedz, MD, of the University of Illinois Chicago. The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and CHEST.

Courtesy CHEST

Dr. LaBedz’s project, “Determinants of Medication Non-Adherence Among Adults With Chronic Obstructive Pulmonary Disease,” aims to use behavioral science theory to identify barriers and facilitators to COPD medication adherence.

Studies suggest racial minorities and individuals of low socioeconomic status (SES) are less likely to be adherent to COPD medications compared with White and high SES patients with COPD. Interventions designed to improve COPD medication adherence must address barriers to adherence experienced by these groups to avoid perpetuating disparities in adherence and downstream outcomes disparities.

For her project, Dr. LaBedz will focus on examining barriers and facilitators of COPD medication adherence, including social determinants of health and other structural barriers faced by these vulnerable populations. She will use the information gained from the qualitative study to design interventions that address the barriers to adherence faced by these groups.

Her long-term goal is to improve COPD medication adherence in vulnerable patients with COPD in order to improve the health status and reduce health disparities experienced by racial/ethnic minority and low SES patients with COPD.

In 2023, CHEST awarded $300,000 in clinical research and community impact grants to 15 individuals. Grant recipients are recognized for their scientifically meritorious achievements, with rigorous metrics to track their project’s progress, and have innovative, novel approaches to addressing their research topic.

CHEST grants have made a difference in patients’ lives by leading to breakthroughs in the treatment and/or management of chest diseases and patient care. This year’s grant-funded projects run the gamut of topics within chest medicine, ranging from lung cancer and COPD to tuberculosis and idiopathic pulmonary fibrosis.

Here’s a glimpse into two of this year’s grant winners and their projects.

For a full list of the 2023 grant winners, visit chestnet.org/grant-recipients.
 

Air pollution in sarcoidosis

This year, the John R. Addrizzo, MD, FCCP Research Grant in Sarcoidosis was awarded to Ali Mustafa, MD, of the Johns Hopkins Hospital in Baltimore, MD, for his project “Air Pollution in Sarcoidosis.”

Courtesy CHEST

The project’s aim is to investigate the feasibility of studying indoor and outdoor air pollution in patients with pulmonary sarcoidosis.

According to Dr. Mustafa’s application, pulmonary sarcoidosis is one of the most common interstitial lung diseases in the United States, and mortality due to sarcoidosis has risen by more than 3% in recent decades.

While the etiology of sarcoidosis remains elusive, evidence points toward a combination of genetic predisposition with external environmental triggers affecting disease onset. One small study of 16 individuals with fibrotic pulmonary sarcoidosis assessed the association between local levels of outdoor air pollutants to clinical outcomes. This study found that increased short-term exposure was associated with increased respiratory symptom severity and worse health-related quality of life.

Additionally, significant health disparities exist in sarcoidosis. Black individuals with sarcoidosis have worse pulmonary function, higher rates of multiorgan disease, and as much as a 12-fold increase in mortality compared with non-Hispanic White individuals with sarcoidosis. Socioeconomic status and Black race have also been associated with increased exposure to air pollution and closer proximity to high toxic emission facilities, suggesting higher exposure to outdoor air pollution.

Racial disparities are present and particularly important in sarcoidosis. Black individuals are more likely to have more advanced disease at diagnosis, have a six-fold increase in hospitalization, and a 12-fold increase in mortality compared with non-Hispanic White individuals with sarcoidosis. Little is known about the drivers of these disparities; however, environmental exposure has been implicated in sarcoidosis pathogenesis and incidence and may be an important contributor.

Dr. Mustafa’s preliminary work suggests disparities in exposure to air pollution among individuals with sarcoidosis may be contributing to inequities in clinical outcomes.
 

Determinants of medication non-adherence among adults with chronic obstructive pulmonary disease

The CHEST/ALA/ATS Respiratory Health Equity Research Award was given to Stephanie LaBedz, MD, of the University of Illinois Chicago. The Respiratory Health Equity Research Award is jointly supported by the American Lung Association, the American Thoracic Society, and CHEST.

Courtesy CHEST

Dr. LaBedz’s project, “Determinants of Medication Non-Adherence Among Adults With Chronic Obstructive Pulmonary Disease,” aims to use behavioral science theory to identify barriers and facilitators to COPD medication adherence.

Studies suggest racial minorities and individuals of low socioeconomic status (SES) are less likely to be adherent to COPD medications compared with White and high SES patients with COPD. Interventions designed to improve COPD medication adherence must address barriers to adherence experienced by these groups to avoid perpetuating disparities in adherence and downstream outcomes disparities.

For her project, Dr. LaBedz will focus on examining barriers and facilitators of COPD medication adherence, including social determinants of health and other structural barriers faced by these vulnerable populations. She will use the information gained from the qualitative study to design interventions that address the barriers to adherence faced by these groups.

Her long-term goal is to improve COPD medication adherence in vulnerable patients with COPD in order to improve the health status and reduce health disparities experienced by racial/ethnic minority and low SES patients with COPD.

The practice of initiating early and adequate nutrition in critically ill patients is a cornerstone of ICU management. Adequate nutrition combats the dangerous catabolic state that accompanies critical illness. A few of the benefits of this practice are a decrease in disease severity with resultant lessened hospital and ICU lengths of stay, reduced infection rates, and a decrease in hospital mortality. Enteral nutrition (EN) is the route of nutritional support most associated with safe and effective provision of enhanced immunologic function and the ability to preserve the patient’s lean body mass while avoiding metabolic and infectious complications.

The practice of initiating early and adequate nutrition in critically ill patients is a cornerstone of ICU management. Adequate nutrition combats the dangerous catabolic state that accompanies critical illness. A few of the benefits of this practice are a decrease in disease severity with resultant lessened hospital and ICU lengths of stay, reduced infection rates, and a decrease in hospital mortality. Enteral nutrition (EN) is the route of nutritional support most associated with safe and effective provision of enhanced immunologic function and the ability to preserve the patient’s lean body mass while avoiding metabolic and infectious complications.

The practice of initiating early and adequate nutrition in critically ill patients is a cornerstone of ICU management. Adequate nutrition combats the dangerous catabolic state that accompanies critical illness. A few of the benefits of this practice are a decrease in disease severity with resultant lessened hospital and ICU lengths of stay, reduced infection rates, and a decrease in hospital mortality. Enteral nutrition (EN) is the route of nutritional support most associated with safe and effective provision of enhanced immunologic function and the ability to preserve the patient’s lean body mass while avoiding metabolic and infectious complications.

Pulmonary physicians and particularly interventional bronchoscopists have been receiving denials when CPT^® codes 31628 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with transbronchial lung biopsy(s), single lobe and 31629 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with transbronchial needle aspiration biopsy(s), trachea, main stem and/or lobar bronchus(i) are billed during the same procedure.

While the difference between a transbronchial forceps biopsy and transbronchial needle biopsy are obvious to bronchoscopists, there has been confusion with payers. This could have been partly on the basis of a CPT Assistant article from March 2021 describing the use of both codes that stated, “Note that performing two types of lung biopsy (forceps and needle aspiration) on the same lesion would be considered unusual and documentation of medical necessity should clearly describe why both types of biopsy were clinically necessary.” This may have been interpreted by coders and/or payers to mean that the two codes should be billed together rarely or not at all. It is also possible that computer-based coding programs (eg, Optum/Encoder Pro, etc) are responsible for these inappropriate denials. There are, however, no NCCI edits that disallow this nor was this the intent of the CPT codes when they were developed.

The previous statement from the CPT Assistant article was clarified in the following sentences, “For example, if needle aspiration were performed and immediate screening of the sample were insufficient for diagnosis, a forceps biopsy would be appropriate and reported separately. On the other hand, if a physician performed a needle aspiration out of concern that the lesion was vascular and found that it was not and proceeded with a forceps biopsy, then the needle aspiration would be integral to the forceps biopsy and not separately reported.” Importantly, with the increasing use of navigational bronchoscopy and robotic bronchoscopy, these codes will be used together more frequently, appropriately, and correctly, especially on distal lesions.

Remember, these codes are used for procedures in a single lobe. If multiple lobes are sampled then CPT codes 31632 and 31633 would be added to 31628 and 31629, respectively. If one is receiving denials for these procedures, coders and payers should be notified of these errors, and denials should be appealed.

Q&A

Question: My practice is wondering if we can use the newer codes for online digital E/M services? We know they are time-based, but we are confused about when they cannot be used. Can you please help? For example, I had an established COPD patient send a message through the electronic health record’s patient portal reporting new symptoms of headache, cough, and sputum production. They asked me to review the chest x-ray that was done two days prior when they went to urgent care. The patient is asking for an assessment and management plan. We message back and forth over the next day for a total of 13 minutes. Three days later, the patient developed more symptoms and then scheduled an office visit. How would I bill for this? 99212-99215 (Established Office E/M) or 99422 (Online digital E/M 11-20 minutes?

Answer: Online Digital E/M services (99421, 99422, 99423) are to be used for established patients, only. They are time-based codes and cumulative up to seven days. They are to be reported for asynchronous communication via HIPAA-compliance secure platforms, such as through the electronic health record portal, portal email, etc. They may not be reported if an E/M occurs within seven days before or after, though the time may be incorporated into the subsequent E/M. These codes are not to be used for communication of test results, scheduling of appointments, or other communication that does not include E/M. In your example, you would report the appropriate Office/ Outpatient Established CPT code (99212-99215).


99421 – Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 5-10 minutes

99422 - Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 11-20 minutes

99423 - Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 21 or more minutes


Question: Is Cardiopulmonary Resuscitation in the Intensive Care Unit considered to be part of Critical Care services? (99291- 99292)? There appears to be confusion in our billing department on this issue.

Answer: 92959 Cardiopulmonary resuscitation is not bundled into 99291-99292. Consider it as a procedure. To code for this service in addition to Critical Care, the time for the CPR must be separate from the time for Critical Care (99291-99292). A separate procedure note must also be documented. There is no minimum time for this service, and a 25 modifier must be included, as well. 92950 reimburses at 4.00 wRVUs and may be reported two times per calendar day.

Originally published in the September 2023 issue of the American Thoracic Society’s ATS Coding & Billing Quarterly. Republished with permission from the American Thoracic Society.

Pulmonary physicians and particularly interventional bronchoscopists have been receiving denials when CPT^® codes 31628 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with transbronchial lung biopsy(s), single lobe and 31629 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with transbronchial needle aspiration biopsy(s), trachea, main stem and/or lobar bronchus(i) are billed during the same procedure.

While the difference between a transbronchial forceps biopsy and transbronchial needle biopsy are obvious to bronchoscopists, there has been confusion with payers. This could have been partly on the basis of a CPT Assistant article from March 2021 describing the use of both codes that stated, “Note that performing two types of lung biopsy (forceps and needle aspiration) on the same lesion would be considered unusual and documentation of medical necessity should clearly describe why both types of biopsy were clinically necessary.” This may have been interpreted by coders and/or payers to mean that the two codes should be billed together rarely or not at all. It is also possible that computer-based coding programs (eg, Optum/Encoder Pro, etc) are responsible for these inappropriate denials. There are, however, no NCCI edits that disallow this nor was this the intent of the CPT codes when they were developed.

The previous statement from the CPT Assistant article was clarified in the following sentences, “For example, if needle aspiration were performed and immediate screening of the sample were insufficient for diagnosis, a forceps biopsy would be appropriate and reported separately. On the other hand, if a physician performed a needle aspiration out of concern that the lesion was vascular and found that it was not and proceeded with a forceps biopsy, then the needle aspiration would be integral to the forceps biopsy and not separately reported.” Importantly, with the increasing use of navigational bronchoscopy and robotic bronchoscopy, these codes will be used together more frequently, appropriately, and correctly, especially on distal lesions.

Remember, these codes are used for procedures in a single lobe. If multiple lobes are sampled then CPT codes 31632 and 31633 would be added to 31628 and 31629, respectively. If one is receiving denials for these procedures, coders and payers should be notified of these errors, and denials should be appealed.

Q&A

Question: My practice is wondering if we can use the newer codes for online digital E/M services? We know they are time-based, but we are confused about when they cannot be used. Can you please help? For example, I had an established COPD patient send a message through the electronic health record’s patient portal reporting new symptoms of headache, cough, and sputum production. They asked me to review the chest x-ray that was done two days prior when they went to urgent care. The patient is asking for an assessment and management plan. We message back and forth over the next day for a total of 13 minutes. Three days later, the patient developed more symptoms and then scheduled an office visit. How would I bill for this? 99212-99215 (Established Office E/M) or 99422 (Online digital E/M 11-20 minutes?

Answer: Online Digital E/M services (99421, 99422, 99423) are to be used for established patients, only. They are time-based codes and cumulative up to seven days. They are to be reported for asynchronous communication via HIPAA-compliance secure platforms, such as through the electronic health record portal, portal email, etc. They may not be reported if an E/M occurs within seven days before or after, though the time may be incorporated into the subsequent E/M. These codes are not to be used for communication of test results, scheduling of appointments, or other communication that does not include E/M. In your example, you would report the appropriate Office/ Outpatient Established CPT code (99212-99215).


99421 – Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 5-10 minutes

99422 - Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 11-20 minutes

99423 - Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 21 or more minutes


Question: Is Cardiopulmonary Resuscitation in the Intensive Care Unit considered to be part of Critical Care services? (99291- 99292)? There appears to be confusion in our billing department on this issue.

Answer: 92959 Cardiopulmonary resuscitation is not bundled into 99291-99292. Consider it as a procedure. To code for this service in addition to Critical Care, the time for the CPR must be separate from the time for Critical Care (99291-99292). A separate procedure note must also be documented. There is no minimum time for this service, and a 25 modifier must be included, as well. 92950 reimburses at 4.00 wRVUs and may be reported two times per calendar day.

Originally published in the September 2023 issue of the American Thoracic Society’s ATS Coding & Billing Quarterly. Republished with permission from the American Thoracic Society.

Pulmonary physicians and particularly interventional bronchoscopists have been receiving denials when CPT^® codes 31628 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with transbronchial lung biopsy(s), single lobe and 31629 Bronchoscopy, rigid or flexible, including fluoroscopic guidance, when performed; with transbronchial needle aspiration biopsy(s), trachea, main stem and/or lobar bronchus(i) are billed during the same procedure.

While the difference between a transbronchial forceps biopsy and transbronchial needle biopsy are obvious to bronchoscopists, there has been confusion with payers. This could have been partly on the basis of a CPT Assistant article from March 2021 describing the use of both codes that stated, “Note that performing two types of lung biopsy (forceps and needle aspiration) on the same lesion would be considered unusual and documentation of medical necessity should clearly describe why both types of biopsy were clinically necessary.” This may have been interpreted by coders and/or payers to mean that the two codes should be billed together rarely or not at all. It is also possible that computer-based coding programs (eg, Optum/Encoder Pro, etc) are responsible for these inappropriate denials. There are, however, no NCCI edits that disallow this nor was this the intent of the CPT codes when they were developed.

The previous statement from the CPT Assistant article was clarified in the following sentences, “For example, if needle aspiration were performed and immediate screening of the sample were insufficient for diagnosis, a forceps biopsy would be appropriate and reported separately. On the other hand, if a physician performed a needle aspiration out of concern that the lesion was vascular and found that it was not and proceeded with a forceps biopsy, then the needle aspiration would be integral to the forceps biopsy and not separately reported.” Importantly, with the increasing use of navigational bronchoscopy and robotic bronchoscopy, these codes will be used together more frequently, appropriately, and correctly, especially on distal lesions.

Remember, these codes are used for procedures in a single lobe. If multiple lobes are sampled then CPT codes 31632 and 31633 would be added to 31628 and 31629, respectively. If one is receiving denials for these procedures, coders and payers should be notified of these errors, and denials should be appealed.

Q&A

Question: My practice is wondering if we can use the newer codes for online digital E/M services? We know they are time-based, but we are confused about when they cannot be used. Can you please help? For example, I had an established COPD patient send a message through the electronic health record’s patient portal reporting new symptoms of headache, cough, and sputum production. They asked me to review the chest x-ray that was done two days prior when they went to urgent care. The patient is asking for an assessment and management plan. We message back and forth over the next day for a total of 13 minutes. Three days later, the patient developed more symptoms and then scheduled an office visit. How would I bill for this? 99212-99215 (Established Office E/M) or 99422 (Online digital E/M 11-20 minutes?

Answer: Online Digital E/M services (99421, 99422, 99423) are to be used for established patients, only. They are time-based codes and cumulative up to seven days. They are to be reported for asynchronous communication via HIPAA-compliance secure platforms, such as through the electronic health record portal, portal email, etc. They may not be reported if an E/M occurs within seven days before or after, though the time may be incorporated into the subsequent E/M. These codes are not to be used for communication of test results, scheduling of appointments, or other communication that does not include E/M. In your example, you would report the appropriate Office/ Outpatient Established CPT code (99212-99215).


99421 – Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 5-10 minutes

99422 - Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 11-20 minutes

99423 - Online digital evaluation and management service, for an established patient, for up to 7 days, cumulative time during the 7 days; 21 or more minutes


Question: Is Cardiopulmonary Resuscitation in the Intensive Care Unit considered to be part of Critical Care services? (99291- 99292)? There appears to be confusion in our billing department on this issue.

Answer: 92959 Cardiopulmonary resuscitation is not bundled into 99291-99292. Consider it as a procedure. To code for this service in addition to Critical Care, the time for the CPR must be separate from the time for Critical Care (99291-99292). A separate procedure note must also be documented. There is no minimum time for this service, and a 25 modifier must be included, as well. 92950 reimburses at 4.00 wRVUs and may be reported two times per calendar day.

Originally published in the September 2023 issue of the American Thoracic Society’s ATS Coding & Billing Quarterly. Republished with permission from the American Thoracic Society.

Looking ahead to 2024, one notable accomplishment of the past 12 months that will guide our organization for years to come was to establish CHEST organizational values. The result of a collaborative process that was led by the Value-Setting Work Group and informed by CHEST leaders, members, and staff, the CHEST values are Community, Inclusivity, Innovation, Advocacy, and Integrity.

The process to arrive at these values was intentionally designed to ensure input from all corners of the organization. Over the course of 5 months, CHEST members had the opportunity to participate in focus groups or submit written feedback about the proposed values. The feedback shaped subsequent iterations of the values that the work group produced, finally arriving at these five.

“These values are meant to be reflective of the CHEST organization and all of its leaders, members, and staff,” said Co-Chair of the Value-Setting Work Group and CHEST Board of Regents Member Nneka Sederstrom, PhD, FCCP. “As a society, we’ve come to a point where we can’t pretend that real life issues don’t matter to our patients and to our members. It’s become a pivotal point in our world for our systems to be clear on who they are. All too often, the question of, ‘Is this our lane?’ comes up. These values are a succinct way to show not only what falls into our ‘lane,’ but that we celebrate where we stand. It was a big undertaking, but seeing the collaboration and passion was exceptional.”

The work group was co-chaired by Dr. Sederstrom and Elizabeth Stigler, PhD, and was supported by David Zielinski, MD, FCCP; Bravein Amalakuhan, MD; Alisha Young, MD; Steven Simpson, MD, FCCP; Nehan Sher, MD; and CHEST staff members, Teresa Rodriguez, Manager, CHEST Annual Meeting; Terri Horton-O’Connell, MSW, Director, Grant and Proposal Development; and Vanessa Rancine, Recruiting Specialist.

Beyond solidifying the five succinct values, the work group strategically defined each value to clarify its intent.
 

• Community: We invest in the support, growth, and development of everyone involved with CHEST, both individually and collectively, and are tireless champions for one another.
• Inclusivity: We cherish the diverse perspectives and experiences of our community members and amplify their unique voices.
• Innovation: We strive for excellence in all that we do with an adaptable and ever-evolving perspective. We pursue bold, future-oriented possibilities for constant improvement and continual growth.
• Advocacy: We courageously and intentionally create and foster positive changes for our patients and their families, our members and staff, and the next generation of CHEST clinicians.
• Integrity: We take pride in acting responsibly with respect, honesty, and accountability that engenders trust.

“With the new values in place, hopefully, our members will feel a shift in how we, as an organization, show up when anything occurs,” Dr. Sederstrom said. “The values will be reflected through community engagement and support and will be deeply integrated into the CHEST Annual Meeting. When someone asks CHEST, ‘Who are you?’ -we can now answer it with certitude.”

Looking ahead to 2024, one notable accomplishment of the past 12 months that will guide our organization for years to come was to establish CHEST organizational values. The result of a collaborative process that was led by the Value-Setting Work Group and informed by CHEST leaders, members, and staff, the CHEST values are Community, Inclusivity, Innovation, Advocacy, and Integrity.

The process to arrive at these values was intentionally designed to ensure input from all corners of the organization. Over the course of 5 months, CHEST members had the opportunity to participate in focus groups or submit written feedback about the proposed values. The feedback shaped subsequent iterations of the values that the work group produced, finally arriving at these five.

“These values are meant to be reflective of the CHEST organization and all of its leaders, members, and staff,” said Co-Chair of the Value-Setting Work Group and CHEST Board of Regents Member Nneka Sederstrom, PhD, FCCP. “As a society, we’ve come to a point where we can’t pretend that real life issues don’t matter to our patients and to our members. It’s become a pivotal point in our world for our systems to be clear on who they are. All too often, the question of, ‘Is this our lane?’ comes up. These values are a succinct way to show not only what falls into our ‘lane,’ but that we celebrate where we stand. It was a big undertaking, but seeing the collaboration and passion was exceptional.”

The work group was co-chaired by Dr. Sederstrom and Elizabeth Stigler, PhD, and was supported by David Zielinski, MD, FCCP; Bravein Amalakuhan, MD; Alisha Young, MD; Steven Simpson, MD, FCCP; Nehan Sher, MD; and CHEST staff members, Teresa Rodriguez, Manager, CHEST Annual Meeting; Terri Horton-O’Connell, MSW, Director, Grant and Proposal Development; and Vanessa Rancine, Recruiting Specialist.

Beyond solidifying the five succinct values, the work group strategically defined each value to clarify its intent.
 

• Community: We invest in the support, growth, and development of everyone involved with CHEST, both individually and collectively, and are tireless champions for one another.
• Inclusivity: We cherish the diverse perspectives and experiences of our community members and amplify their unique voices.
• Innovation: We strive for excellence in all that we do with an adaptable and ever-evolving perspective. We pursue bold, future-oriented possibilities for constant improvement and continual growth.
• Advocacy: We courageously and intentionally create and foster positive changes for our patients and their families, our members and staff, and the next generation of CHEST clinicians.
• Integrity: We take pride in acting responsibly with respect, honesty, and accountability that engenders trust.

“With the new values in place, hopefully, our members will feel a shift in how we, as an organization, show up when anything occurs,” Dr. Sederstrom said. “The values will be reflected through community engagement and support and will be deeply integrated into the CHEST Annual Meeting. When someone asks CHEST, ‘Who are you?’ -we can now answer it with certitude.”

Looking ahead to 2024, one notable accomplishment of the past 12 months that will guide our organization for years to come was to establish CHEST organizational values. The result of a collaborative process that was led by the Value-Setting Work Group and informed by CHEST leaders, members, and staff, the CHEST values are Community, Inclusivity, Innovation, Advocacy, and Integrity.

The process to arrive at these values was intentionally designed to ensure input from all corners of the organization. Over the course of 5 months, CHEST members had the opportunity to participate in focus groups or submit written feedback about the proposed values. The feedback shaped subsequent iterations of the values that the work group produced, finally arriving at these five.

“These values are meant to be reflective of the CHEST organization and all of its leaders, members, and staff,” said Co-Chair of the Value-Setting Work Group and CHEST Board of Regents Member Nneka Sederstrom, PhD, FCCP. “As a society, we’ve come to a point where we can’t pretend that real life issues don’t matter to our patients and to our members. It’s become a pivotal point in our world for our systems to be clear on who they are. All too often, the question of, ‘Is this our lane?’ comes up. These values are a succinct way to show not only what falls into our ‘lane,’ but that we celebrate where we stand. It was a big undertaking, but seeing the collaboration and passion was exceptional.”

The work group was co-chaired by Dr. Sederstrom and Elizabeth Stigler, PhD, and was supported by David Zielinski, MD, FCCP; Bravein Amalakuhan, MD; Alisha Young, MD; Steven Simpson, MD, FCCP; Nehan Sher, MD; and CHEST staff members, Teresa Rodriguez, Manager, CHEST Annual Meeting; Terri Horton-O’Connell, MSW, Director, Grant and Proposal Development; and Vanessa Rancine, Recruiting Specialist.

Beyond solidifying the five succinct values, the work group strategically defined each value to clarify its intent.
 

• Community: We invest in the support, growth, and development of everyone involved with CHEST, both individually and collectively, and are tireless champions for one another.
• Inclusivity: We cherish the diverse perspectives and experiences of our community members and amplify their unique voices.
• Innovation: We strive for excellence in all that we do with an adaptable and ever-evolving perspective. We pursue bold, future-oriented possibilities for constant improvement and continual growth.
• Advocacy: We courageously and intentionally create and foster positive changes for our patients and their families, our members and staff, and the next generation of CHEST clinicians.
• Integrity: We take pride in acting responsibly with respect, honesty, and accountability that engenders trust.

“With the new values in place, hopefully, our members will feel a shift in how we, as an organization, show up when anything occurs,” Dr. Sederstrom said. “The values will be reflected through community engagement and support and will be deeply integrated into the CHEST Annual Meeting. When someone asks CHEST, ‘Who are you?’ -we can now answer it with certitude.”

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.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.