Neurology Reviews

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Regular moderate to vigorous physical activity predicts larger brain size in key regions, including gray and white matter and the hippocampus, new data suggest. 

METHODOLOGY: 

• The potential neuroprotective effects of regular physical activity on brain structure are unclear despite reported links between physical activity and reduced dementia risk. 
• To investigate, researchers analyzed MRI brain scans from 10,125 healthy adults (mean age, 53 years; 52% male) who self-reported their level of physical activity.
• Moderate to vigorous physical activities, defined as those increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes, adjusting for covariates.
• The threshold for defining physically active (vs nonactive) adults was intentionally set at 2.5 days per week, a level far lower than current guidelines.

TAKEAWAY:

• Three quarters of the cohort reported engaging in moderate to vigorous physical activity approximately 4 days per week. 
• Physically active adults tended to be younger, with a higher proportion of White individuals, and with lower rates of hypertension and type 2 diabetes. 
• After adjusting for multiple factors, increased days of moderate to vigorous activity correlated with larger normalized brain volume in multiple regions including total gray matter; white matter; hippocampus; and frontal, parietal, and occipital lobes. 

IN PRACTICE: 

“We found that even moderate levels of physical activity, such as taking fewer than 4,000 steps a day, can have a positive effect on brain health. This is much less than the often-suggested 10,000 steps, making it a more achievable goal for many people,” co-author David Merrill, MD, with Pacific Brain Health Center, Santa Monica, California, said in a statement. 

SOURCE: 

The study, with first author Cyrus A. Raji, MD, PhD, Washington University School of Medicine, St. Louis, was published online in the Journal of Alzheimer’s Disease.

LIMITATIONS: 

Participants self-reported physical activity in the past 2 weeks, which does not reflect a lifetime of activity levels. The correlation identified between physical activity and brain volumes may not be solely attributable to physical activity alone. 

DISCLOSURES: 

The study received funding from several health centers and foundations. Dr. Raji consults for Brainreader ApS, Neurevolution LLC, Apollo Health, Voxelwise Imaging Technology, and Pacific Neuroscience Foundation and is an editorial board member of the Journal of Alzheimer’s Disease but was not involved in the peer-review process.

A version of this article appeared on Medscape.com.

TOPLINE:

Regular moderate to vigorous physical activity predicts larger brain size in key regions, including gray and white matter and the hippocampus, new data suggest. 

METHODOLOGY: 

• The potential neuroprotective effects of regular physical activity on brain structure are unclear despite reported links between physical activity and reduced dementia risk. 
• To investigate, researchers analyzed MRI brain scans from 10,125 healthy adults (mean age, 53 years; 52% male) who self-reported their level of physical activity.
• Moderate to vigorous physical activities, defined as those increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes, adjusting for covariates.
• The threshold for defining physically active (vs nonactive) adults was intentionally set at 2.5 days per week, a level far lower than current guidelines.

TAKEAWAY:

• Three quarters of the cohort reported engaging in moderate to vigorous physical activity approximately 4 days per week. 
• Physically active adults tended to be younger, with a higher proportion of White individuals, and with lower rates of hypertension and type 2 diabetes. 
• After adjusting for multiple factors, increased days of moderate to vigorous activity correlated with larger normalized brain volume in multiple regions including total gray matter; white matter; hippocampus; and frontal, parietal, and occipital lobes. 

IN PRACTICE: 

“We found that even moderate levels of physical activity, such as taking fewer than 4,000 steps a day, can have a positive effect on brain health. This is much less than the often-suggested 10,000 steps, making it a more achievable goal for many people,” co-author David Merrill, MD, with Pacific Brain Health Center, Santa Monica, California, said in a statement. 

SOURCE: 

The study, with first author Cyrus A. Raji, MD, PhD, Washington University School of Medicine, St. Louis, was published online in the Journal of Alzheimer’s Disease.

LIMITATIONS: 

Participants self-reported physical activity in the past 2 weeks, which does not reflect a lifetime of activity levels. The correlation identified between physical activity and brain volumes may not be solely attributable to physical activity alone. 

DISCLOSURES: 

The study received funding from several health centers and foundations. Dr. Raji consults for Brainreader ApS, Neurevolution LLC, Apollo Health, Voxelwise Imaging Technology, and Pacific Neuroscience Foundation and is an editorial board member of the Journal of Alzheimer’s Disease but was not involved in the peer-review process.

A version of this article appeared on Medscape.com.

TOPLINE:

Regular moderate to vigorous physical activity predicts larger brain size in key regions, including gray and white matter and the hippocampus, new data suggest. 

METHODOLOGY: 

• The potential neuroprotective effects of regular physical activity on brain structure are unclear despite reported links between physical activity and reduced dementia risk. 
• To investigate, researchers analyzed MRI brain scans from 10,125 healthy adults (mean age, 53 years; 52% male) who self-reported their level of physical activity.
• Moderate to vigorous physical activities, defined as those increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes, adjusting for covariates.
• The threshold for defining physically active (vs nonactive) adults was intentionally set at 2.5 days per week, a level far lower than current guidelines.

TAKEAWAY:

• Three quarters of the cohort reported engaging in moderate to vigorous physical activity approximately 4 days per week. 
• Physically active adults tended to be younger, with a higher proportion of White individuals, and with lower rates of hypertension and type 2 diabetes. 
• After adjusting for multiple factors, increased days of moderate to vigorous activity correlated with larger normalized brain volume in multiple regions including total gray matter; white matter; hippocampus; and frontal, parietal, and occipital lobes. 

IN PRACTICE: 

“We found that even moderate levels of physical activity, such as taking fewer than 4,000 steps a day, can have a positive effect on brain health. This is much less than the often-suggested 10,000 steps, making it a more achievable goal for many people,” co-author David Merrill, MD, with Pacific Brain Health Center, Santa Monica, California, said in a statement. 

SOURCE: 

The study, with first author Cyrus A. Raji, MD, PhD, Washington University School of Medicine, St. Louis, was published online in the Journal of Alzheimer’s Disease.

LIMITATIONS: 

Participants self-reported physical activity in the past 2 weeks, which does not reflect a lifetime of activity levels. The correlation identified between physical activity and brain volumes may not be solely attributable to physical activity alone. 

DISCLOSURES: 

The study received funding from several health centers and foundations. Dr. Raji consults for Brainreader ApS, Neurevolution LLC, Apollo Health, Voxelwise Imaging Technology, and Pacific Neuroscience Foundation and is an editorial board member of the Journal of Alzheimer’s Disease but was not involved in the peer-review process.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients aged 50 years or older with clinically apparent Helicobacter pylori infection (CAHPI) have an 11% increased risk for Alzheimer’s disease (AD), results of a large and lengthy population-based study suggest.

METHODOLOGY: 

• Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
• The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
• Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.

TAKEAWAY: 

• Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
• The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
• Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
• The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).

IN PRACTICE:

“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.

SOURCE:

The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.

LIMITATIONS:

Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.

DISCLOSURES:

The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Selecting a treatment plan to deal with acute migraine attacks can be like putting together a toolkit of possible therapies, individualized for each patient, one expert said.

The toolkit should comprise reliable treatments that patients know are going to work and that act quickly, allowing them to get back to functioning normally in their daily lives, said Jessica Ailani, MD, during a talk at the 17th European Headache Congress held recently in Barcelona, Spain. 

“Everyone with migraine needs acute treatment,” Dr. Ailani, who is a clinical professor of neurology at MedStar Georgetown University Hospital and director of the Georgetown Headache Center, Washington, DC, noted. “Sometimes we can reduce acute treatment with preventative agents, but some disability will remain, so we have to focus on good acute treatment, and this becomes more complex if a person has a lot of comorbidities, which is common in older patients.” 

In selecting suitable treatments for migraine, consideration has to be given to the patient profile, any other conditions they have, speed of onset of the migraine attack, length of the attack, associated symptoms, and side effects of the medications, she said. 
 

A Complex Case

As an example, Dr. Ailani described the process she used to treat one of her patients who had frequent severe migraines and other issues causing difficult decisions when selecting medications — a woman in her late 60s with several other comorbidities.

“This is the kind of case I see on a daily basis and which keeps me up at night,” she said. “Many times in clinical practice, we see complex cases like this, and through the course of a year, we may try every treatment option we have in a patient like this.”

On the first presentation, the patient had a chronic migraine with severe headaches every day. She had a history of previous cervical discectomy with fusion surgery; uncontrolled hypertension, for which she was taking an angiotensin blocker; high cholesterol, for which she was taking a statin; and diabetes with an A1c of 8. She did not smoke or drink alcohol, exercised moderately, and her body mass index was in a good range. 

“Before a patient ever sees a doctor for their migraine, they will have already tried a lot of different things. Most people are already using NSAIDs and acetaminophen, the most commonly used treatments for acute migraine,” Dr. Ailani explains.

Her patient was taking a triptan and the barbiturate, butalbital. Dr. Ailani notes that the triptan is very effective, but in the United States, they are not available over the counter, and the patient is only allowed nine doses per month on her insurance, so she was supplementing with butalbital. 

Over the course of a year, Dr. Ailani got her off the butalbital and started her on onabotulinum toxin A for migraine prevention, which reduced her headache days to about 15 per month (8 severe). She then added the anti-calcitonin gene-related peptide (CGRP) monoclonal antibody, galcanezumab, as another preventative, which further reduced the headache days down to 8-10 days per month (all migraine). 

The attacks are rapid onset and can last multiple days. They come with photophobia and phonophobia and cause her to be bedridden, she noted. 

“I was still worried about this frequency of headache and the fact she was using a triptan for acute treatment when she had uncontrolled hypertension and other cardiovascular risk factors, Dr. Ailani commented. 

She explained that triptans are generally not used in individuals aged over 65 years because of a lack of data in this age group. They are also contraindicated in patients with cardiovascular (CV) disease, and caution is advised in patients with CV risk factors. Noting that migraine is an independent risk factor for stroke in healthy individuals, and this patient already had three other major risk factors for stroke, Dr. Ailani said she did not think a triptan was the best option. 

When triptans do not work, Dr. Ailani said she thinks about dihydroergotamine, which she describes as “a great drug for long-lasting migraine” as it tends to have a sustained response. But it also has vasoconstrictive effects and can increase blood pressure, so it was not suitable for this patient. 

CV risk is also an issue with nonsteroidal anti-inflammatory drugs (NSAIDs), one of the staple treatments for acute migraine.

“NSAIDs are available over the counter, inexpensive, quite effective, and have minimal immediate side effects,” Dr. Ailani said. But long-term adverse events include CV events, particularly in those who already have CV risk factors, and it is now thought that NSAIDs actually carry more CV risk than triptans.

She noted that out of all the NSAIDs, celecoxib carries the lowest CV risk, and in the United States, it is available as a liquid formulation. There is also a study of ketorolac nasal spray showing it to be as effective as sumatriptan nasal spray for acute migraine.

As her patient was still going to the emergency room (ER) quite frequently at this point, Dr. Ailani prescribed ketorolac nasal spray as an emergency rescue medication, which did help to reduce ER visits but did not solve the acute treatment problem.

The next option she tried was the CGRP antagonists or “gepants” because of their good tolerability.

Because her patient had long attacks, Dr. Ailani said her first choice gepant was rimegepant as it has a long half-life.

She noted that in patients who have frequent migraine attacks (> 6 migraine days per month), using rimegepant as needed has been shown to lead to migraine frequency declining over time. “This shows that if we treat acute attacks properly, we can minimize the risk of chronic migraine.”

She pointed out that if a patient has prodrome that is easy to identify or has short attacks, ubrogepant may be a good option, having shown effectiveness in preventing or reducing the onset of the headache in the recently reported PRODROME trial when given the day before migraine starts.

Then there is also zavegepant, which is available as a nasal spray, so it is a good option for patients with nausea and vomiting. Dr. Ailani suggested that zavegepant as a third-generation gepant may be worth trying in patients who have tried the other gepants, as it is a different type of molecule.

For this patient, neither rimegepant nor ubrogepant worked. “We tried treating in the prodrome, when the pain was starting, adding to other treatments, but she is not a ‘gepant’ responder. We have yet to try zavegepant,” she said.

The next consideration was lasmiditan. “This patient is a triptan responder and lasmiditan is a 5HT1 agonist, so it makes sense to try this. Also, it doesn’t have a vasoconstrictor effect as it doesn’t work on the blood vessels, so it is safe for patients with high blood pressure,” Dr. Ailani noted.

She pointed out, however, that lasmiditan has become a rescue medication in her practice because of side effect issues such as dizziness and sleepiness.

But Dr. Ailani said she has learned how to use the medication to minimize the side effects, by increasing the dose slowly and advising patients to take it later in the day.

“We start with 50 mg for a few doses then increase to 100 mg. This seems to build tolerability.”

Her patient has found good relief from lasmiditan 100 mg, but she can’t take it during the day as it makes her sleepy.

As a last resort, Dr. Ailani went back to metoclopramide, which she described as “a tried and tested old-time drug.”

While this does not make the patient sleepy, it has other adverse effects limiting the frequency of its use, she noted. “I ask her to try to limit it to twice a week, and this has been pretty effective. She can function when she uses it.” 

Dr. Ailani also points out that neuromodulation should be in everyone’s tool kit. “So, we added an external combined occipital and trigeminal (eCOT device) neurostimulation device.”

The patient’s tool kit now looks like this:

• Neuromodulation device and meditation at first sign of an attack.
• Add metoclopramide 10 mg and acetaminophen 1000 mg.
• If the attack lasts into the second day, add lasmiditan 100 mg in the evening of the second day (limit 8 days a month).
• If the patient has a sudden onset severe migraine with nausea and vomiting that might make her go to the ER, add in ketorolac nasal spray (not > 5 days per month).

Dr. Ailani noted that other patients will need different toolkits, and in most cases, it is recommended to think about “situational prevention” for times when migraine attacks are predictable, which may include air travel, high-stress times (holidays, etc.), occasions when alcohol will be consumed, and at times of certain weather triggers.

Dr. Ailani disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

A new federal rule opens the door for physicians in California and Texas to take advantage of student loan forgiveness, possibly bringing much-needed relief to those with cumbersome debt loads after repayments resumed last month. However, the timing is critical, as some doctors may need to consolidate their loans by December 31 to remain eligible.

Updated guidelines for the Public Service Loan Forgiveness Program (PSLF) took effect in July, expanding the number of potential borrowers who could have their federal student loan balances wiped clean after working full time in a government or nonprofit role and making 120 monthly loan payments.

But loan forgiveness also hinges on having the correct employment type and requires applicants to be a “direct hire” of the organization. State laws in California and Texas prohibit nonprofit hospitals and health care entities from directly hiring physicians — a loophole that has barred doctors in those locations from applying.

Both states’ medical and hospital associations worked with the US Department of Education (DOE) to offer an exception. California and Texas physicians can now satisfy the employment type condition by having a written contract or medical staff privileges with a nonprofit hospital or facility, even if the physician is part of a for-profit sole proprietorship, partnership, or medical group.

Eligible loans cannot be in default and must have been received through the Direct Loan Program, which includes Parent PLUS loans. Doctors with non-qualifying student loans, such as Federal Family Education Loans, can become PSLF-eligible and have past time worked counted toward the requirements if they consolidate into a direct loan by December 31.

The California Medical Association (CMA) has an online guide to help doctors and employers navigate the new rules.

The change comes just in time because California and Texas need to expand their physician workforces by tens of thousands over the next decade. “This program will allow us to retain and recruit new physicians to our states to address our growing physician shortages and access to care challenges for the patients who need us most,” Texas Medical Association president Rick W. Snyder II, MD, said in a statement.

Physicians should use the PSLF Help Tool to complete the forgiveness application, said Ashley Harrington, senior advisor at the DOE. During a free on-demand webinar hosted by CMA, she said the form has been streamlined and will ask applicants to list the nonprofit entity where they provide care, its employer identification number, the length of time worked there, and the average hours worked per week. The employer must sign to certify the physician’s reported hours.

Ideally, physicians should submit a PSLF form annually or each time they change jobs, but they can also wait until the end of the 10 years to submit the form, said Ms. Harrington.

With the average medical education loan debt exceeding $200,000, CMA president Donaldo Hernandez, MD, said the rule will ensure low-income and minority students can consider medical careers.

California family medicine physician Ashley Paydar, DO, said that she has already applied for PSLF and found the process relatively easy. While she awaits final approval, she’s planning for the future. “Loan forgiveness will allow me to do a fellowship and save for my children›s college so they can pursue higher education without the debt,” she said.

Still, employers have no legal obligation to certify physicians’ hours, and many may express hesitation as they try to understand the new guidelines, said Long Do, JD, partner at Athene Law in San Francisco and speaker during the webinar. He urged physicians to have patience when working through the application process.

A version of this article appeared on Medscape.com.

A new federal rule opens the door for physicians in California and Texas to take advantage of student loan forgiveness, possibly bringing much-needed relief to those with cumbersome debt loads after repayments resumed last month. However, the timing is critical, as some doctors may need to consolidate their loans by December 31 to remain eligible.

Updated guidelines for the Public Service Loan Forgiveness Program (PSLF) took effect in July, expanding the number of potential borrowers who could have their federal student loan balances wiped clean after working full time in a government or nonprofit role and making 120 monthly loan payments.

But loan forgiveness also hinges on having the correct employment type and requires applicants to be a “direct hire” of the organization. State laws in California and Texas prohibit nonprofit hospitals and health care entities from directly hiring physicians — a loophole that has barred doctors in those locations from applying.

Both states’ medical and hospital associations worked with the US Department of Education (DOE) to offer an exception. California and Texas physicians can now satisfy the employment type condition by having a written contract or medical staff privileges with a nonprofit hospital or facility, even if the physician is part of a for-profit sole proprietorship, partnership, or medical group.

Eligible loans cannot be in default and must have been received through the Direct Loan Program, which includes Parent PLUS loans. Doctors with non-qualifying student loans, such as Federal Family Education Loans, can become PSLF-eligible and have past time worked counted toward the requirements if they consolidate into a direct loan by December 31.

The California Medical Association (CMA) has an online guide to help doctors and employers navigate the new rules.

The change comes just in time because California and Texas need to expand their physician workforces by tens of thousands over the next decade. “This program will allow us to retain and recruit new physicians to our states to address our growing physician shortages and access to care challenges for the patients who need us most,” Texas Medical Association president Rick W. Snyder II, MD, said in a statement.

Physicians should use the PSLF Help Tool to complete the forgiveness application, said Ashley Harrington, senior advisor at the DOE. During a free on-demand webinar hosted by CMA, she said the form has been streamlined and will ask applicants to list the nonprofit entity where they provide care, its employer identification number, the length of time worked there, and the average hours worked per week. The employer must sign to certify the physician’s reported hours.

Ideally, physicians should submit a PSLF form annually or each time they change jobs, but they can also wait until the end of the 10 years to submit the form, said Ms. Harrington.

With the average medical education loan debt exceeding $200,000, CMA president Donaldo Hernandez, MD, said the rule will ensure low-income and minority students can consider medical careers.

California family medicine physician Ashley Paydar, DO, said that she has already applied for PSLF and found the process relatively easy. While she awaits final approval, she’s planning for the future. “Loan forgiveness will allow me to do a fellowship and save for my children›s college so they can pursue higher education without the debt,” she said.

Still, employers have no legal obligation to certify physicians’ hours, and many may express hesitation as they try to understand the new guidelines, said Long Do, JD, partner at Athene Law in San Francisco and speaker during the webinar. He urged physicians to have patience when working through the application process.

A version of this article appeared on Medscape.com.

A new federal rule opens the door for physicians in California and Texas to take advantage of student loan forgiveness, possibly bringing much-needed relief to those with cumbersome debt loads after repayments resumed last month. However, the timing is critical, as some doctors may need to consolidate their loans by December 31 to remain eligible.

Updated guidelines for the Public Service Loan Forgiveness Program (PSLF) took effect in July, expanding the number of potential borrowers who could have their federal student loan balances wiped clean after working full time in a government or nonprofit role and making 120 monthly loan payments.

But loan forgiveness also hinges on having the correct employment type and requires applicants to be a “direct hire” of the organization. State laws in California and Texas prohibit nonprofit hospitals and health care entities from directly hiring physicians — a loophole that has barred doctors in those locations from applying.

Both states’ medical and hospital associations worked with the US Department of Education (DOE) to offer an exception. California and Texas physicians can now satisfy the employment type condition by having a written contract or medical staff privileges with a nonprofit hospital or facility, even if the physician is part of a for-profit sole proprietorship, partnership, or medical group.

Eligible loans cannot be in default and must have been received through the Direct Loan Program, which includes Parent PLUS loans. Doctors with non-qualifying student loans, such as Federal Family Education Loans, can become PSLF-eligible and have past time worked counted toward the requirements if they consolidate into a direct loan by December 31.

The California Medical Association (CMA) has an online guide to help doctors and employers navigate the new rules.

The change comes just in time because California and Texas need to expand their physician workforces by tens of thousands over the next decade. “This program will allow us to retain and recruit new physicians to our states to address our growing physician shortages and access to care challenges for the patients who need us most,” Texas Medical Association president Rick W. Snyder II, MD, said in a statement.

Physicians should use the PSLF Help Tool to complete the forgiveness application, said Ashley Harrington, senior advisor at the DOE. During a free on-demand webinar hosted by CMA, she said the form has been streamlined and will ask applicants to list the nonprofit entity where they provide care, its employer identification number, the length of time worked there, and the average hours worked per week. The employer must sign to certify the physician’s reported hours.

Ideally, physicians should submit a PSLF form annually or each time they change jobs, but they can also wait until the end of the 10 years to submit the form, said Ms. Harrington.

With the average medical education loan debt exceeding $200,000, CMA president Donaldo Hernandez, MD, said the rule will ensure low-income and minority students can consider medical careers.

California family medicine physician Ashley Paydar, DO, said that she has already applied for PSLF and found the process relatively easy. While she awaits final approval, she’s planning for the future. “Loan forgiveness will allow me to do a fellowship and save for my children›s college so they can pursue higher education without the debt,” she said.

Still, employers have no legal obligation to certify physicians’ hours, and many may express hesitation as they try to understand the new guidelines, said Long Do, JD, partner at Athene Law in San Francisco and speaker during the webinar. He urged physicians to have patience when working through the application process.

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

This discussion was recorded on November 16, 2023. This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. Joining me today is Dr. Brian J. Miller, a hospitalist with Johns Hopkins University School of Medicine and a health policy expert, to discuss the current and renewed interest in physician-owned hospitals.

Welcome, Dr. Miller. It’s a pleasure to have you join me today.

Brian J. Miller, MD, MBA, MPH: Thank you for having me.

History and Controversies Surrounding Physician-Owned Hospitals

Dr. Glatter: I want to start off by having you describe the history associated with the moratorium on new physician-owned hospitals in 2010 that’s related ultimately to the Affordable Care Act, but also, the current and renewed media interest in physician-owned hospitals that’s linked to recent congressional hearings last month.

Dr. Miller: Thank you. I should note that my views are my own and don’t represent those of Hopkins or the American Enterprise Institute, where I’m a nonresident fellow nor the Medicare Payment Advisory Commission, of which I’m a Commissioner.

The story about physician-owned hospitals is an interesting one. Hospitals turned into health systems in the 1980s and 1990s, and physicians started to shift purely from an independent model into a more organized group practice or employed model. Physicians realized that they wanted an alternative operating arrangement. You want a choice of how you practice and what your employment is. And as community hospitals started to buy physicians and also establish their own physician groups de novo, physicians opened physician-owned hospitals.

Physician-owned hospitals fell into a couple of buckets. One is what we call community hospitals, or what the antitrust lawyers would call general acute care hospitals: those offering emergency room (ER) services, labor and delivery, primary care, general surgery — the whole regular gamut, except that some of the owners were physicians.

The other half of the marketplace ended up being specialty hospitals: those built around a specific medical specialty and series of procedures and chronic care. For example, cardiac hospitals often do CABG, TAVR, maybe abdominal aortic aneurysm (triple A) repairs, and they have cardiology clinics, cath labs, a cardiac intensive care unit (ICU), ER, etc. There were also orthopedic surgical specialty hospitals, which were sort of like an ambulatory surgery center (ASC) plus several beds. Then there were general surgical specialty hospitals. At one point, there were some women’s health–focused specialty hospitals.

The hospital industry, of course, as you can understand, didn’t exactly like this. They had a series of concerns about what we would historically call cherry-picking or lemon-dropping of patients. They were worried that physician-owned facilities didn’t want to serve public payer patients, and there was a whole series of reports and investigations.

Around the time the Affordable Care Act passed, the hospital industry had many concerns about physician-owned specialty hospitals, and there was a moratorium as part of the 2003 Medicare Modernization Act. As part of the bargaining over the hospital industry support for the Affordable Care Act, they traded their support for, among other things, their number one priority, which is a statutory prohibition on new or expanded physician-owned hospitals from participating in Medicare. That included both physician-owned community hospitals and physician-owned specialty hospitals.

Dr. Glatter: I guess the main interest is that, when physicians have an ownership or a stake in the hospital, this is what the Stark laws obviously were aimed at. That was part of the impetus to prevent physicians from referring patients where they had an ownership stake. Certainly, hospitals can be owned by attorneys and nonprofit organizations, and certainly, ASCs can be owned by physicians. There is an ongoing issue in terms of physicians not being able to have an ownership stake. In terms of equity ownership, we know that certain other models allow this, but basically, it sounds like this is an issue with Medicare. That seems to be the crux of it, correct?

Dr. Miller: Yes. I would also add that it’s interesting when we look at other professions. When we look at lawyers, nonlawyers are actually not allowed to own an equity stake in a law practice. In many other professions, you either have corporate ownership or professional ownership, or the alternative is you have only professional ownership. I would say the hospital industry is one of the few areas where professional ownership not only is not allowed, but also is statutorily prohibited functionally through the Medicare program.

Unveiling the Dynamics of Hospital Ownership

Dr. Glatter: A recent study done by two PhDs looked at 2019 data on 20 of the most expensive diagnosis-related groups (DRGs). It examined the cost savings, and we’re talking over $1 billion in expenditures when you look at the data from general acute care hospitals vs physician-owned hospitals. This is what appears to me to be a key driver of the push to loosen restrictions on physician-owned hospitals. Isn’t that correct?

Dr. Miller: I would say that’s one of many components. There’s more history to this issue. I remember sitting at a think tank talking to someone several years ago about hospital consolidation as an issue. We went through the usual levers that us policy wonks go through. We talked about antitrust enforcement, certificate of need, rising hospital costs from consolidation, lower quality (or at least no quality gains, as shown by a New England Journal of Medicine study), and decrements in patient experience that result from the diseconomies of scale. They sort of pooh-poohed many of the policy ideas. They basically said that there was no hope for hospital consolidation as an issue.

Well, what about physician ownership? I started with my research team to comb through the literature and found a variety of studies — some of which were sort of entertaining, because they’d do things like study physician-owned specialty hospitals, nonprofit-owned specialty hospitals, and for-profit specialty hospitals and compare them with nonprofit or for-profit community hospitals, and then say physician-owned hospitals that were specialty were bad.

They mixed ownership and service markets right there in so many ways, I’m not sure where to start. My team did a systematic review of around 30 years of research, looking at the evidence base in this space. We found a couple of things.

We found that physician-owned community hospitals did not have a cost or quality difference, meaning that there was no definitive evidence that the physician-owned community hospitals were cheaper based on historical evidence, which was very old. That means there’s not specific harm from them. When you permit market entry for community hospitals, that promotes competition, which results in lower prices and higher quality.

Then we also looked at the specialty hospital markets — surgical specialty hospitals, orthopedic surgical specialty hospitals, and cardiac hospitals. We noted for cardiac hospitals, there wasn’t clear evidence about cost savings, but there was definitive evidence of higher quality, from things like 30-day mortality for significant procedures like treatment of acute MI, triple A repair, stuff like that.

For orthopedic surgical specialty hospitals, we noted lower costs and higher quality, which again fits with operationally what we would know. If you have a facility that’s doing 20 total hips a day, you’re creating a focused factory. Just like if you think about it for interventional cardiology, your boards have a minimum number of procedures that you have to do to stay certified because we know about the volume-quality relationship.

Then we looked at general surgical specialty hospitals. There wasn’t enough evidence to make a conclusive thought about costs, and there was a clear trend toward higher quality. I would say this recent study is important, but there is a whole bunch of other literature out there, too.

Exploring the Scope of Emergency Care in Physician-Owned Hospitals

Dr. Glatter: Certainly, your colleague Wang from Johns Hopkins has done important research in this sector. The paper, “Reconsidering the Ban on Physician-Owned Hospitals to Combat Consolidation,” by you and several colleagues, mentions and highlights the issues that you just described. I understand that it’s going to be published in the NYU Journal of Legislation and Public Policy.

One thing I want to bring up — and this is an important issue — is that the risk for patients has been talked about by the American Hospital Association and the Federation of American Hospitals, in terms of limited or no emergency services at such physician-owned hospitals and having to call 911 when patients need emergent care or stabilization. That’s been the rebuttal, along with an Office of Inspector General (OIG) report from 2008. Almost, I guess, three quarters of the patients that needed emergent care got this at publicly funded hospitals.

Dr. Miller: I’m familiar with the argument about emergency care. If you actually go and look at it, it differs by specialty market. Physician-owned community hospitals have ERs because that’s how they get their business. If you are running a hospital medicine floor, a general surgical specialty floor, you have a labor delivery unit, a primary care clinic, and a cardiology clinic. You have all the things that all the other hospitals have. The physician-owned community hospitals almost uniformly have an ER.

When you look at the physician-owned specialty hospitals, it’s a little more granular. If you look at the cardiac hospitals, they have ERs. They also have cardiac ICUs, operating rooms, etc. The area where the hospital industry had concerns — which I think is valid to point out — is that physician-owned orthopedic surgical specialty hospitals don’t have ERs. But this makes sense because of what that hospital functionally is: a factory for whatever the scope of procedures is, be it joint replacements or shoulder arthroscopy. The orthopedic surgical specialty hospital is like an ASC plus several hospital beds. Many of those did not have ERs because clinically it didn’t make sense.

What’s interesting, though, is that the hospital industry also operates specialty hospitals. If you go into many of the large systems, they have cardiac specialty hospitals and cancer specialty hospitals. I would say that some of them have ERs, as they appropriately should, and some of those specialty hospitals do not. They might have a community hospital down the street that’s part of that health system that has an ER, but some of the specialty hospitals don’t necessarily have a dedicated ER.

I agree, that’s a valid concern. I would say, though, the question is, what are the scope of services in that hospital? Is an ER required? Community hospitals should have ERs. It makes sense also for a cardiac hospital to have one. If you’re running a total joint replacement factory, it might not make clinical sense.

Dr. Glatter: The patients who are treated at that hospital, if they do have emergent conditions, need to have board-certified emergency physicians treating them, in my view because I’m an ER physician. Having surgeons that are not emergency physicians staff a department at a specialty orthopedic hospital or, say, a cancer hospital is not acceptable from my standpoint. That›s my opinion and recommendation, coming from emergency medicine.

Dr. Miller: I would say that anesthesiologists are actually highly qualified in critical care. The question is about clinical decompensation; if you’re doing a procedure, you have an anesthesiologist right there who is capable of critical care. The function of the ER is to either serve as a window into the hospital for patient volume or to serve as a referral for emergent complaints.

Dr. Glatter: An anesthesiologist — I’ll take issue with that — does not have the training of an emergency physician in terms of scope of practice.

Dr. Miller: My anesthesiology colleagues would probably disagree for managing an emergency during an operating room case.

Dr. Glatter: Fair enough, but I think in the general sense. The other issue is that, in terms of emergent responses to patients that decompensate, when you have to transfer a patient, that violates Medicare requirements. How is that even a valid issue or argument if you’re going to have to transfer a patient from your specialty hospital? That happens. Again, I know that you’re saying these hospitals are completely independent and can function, stabilize patients, and treat emergencies, but that’s not the reality across the country, in my opinion.

Dr. Miller: I don’t think that’s the case for the physician-owned specialty cardiac hospitals, for starters. Many of those have ICUs in addition to operating rooms as a matter of routine in addition to ERs. I don’t think that’s the case for physician-owned community hospitals, which have ERs, ICUs, medicine floors, and surgical floors. Physician-owned community hospitals are around half the market. Of that remaining market, a significant percentage are cardiac hospitals. If you’re taking an issue with orthopedic surgical specialty hospitals, that’s a clinical operational question that can and should be answered.

I’d also posit that the nonprofit and for-profit hospital industries also operate specialty hospitals. Any of these questions, we shouldn’t just be asking about physician-owned facilities; we should be asking about them across ownership types, because we’re talking about scope of service and quality and safety. The ownership in that case doesn’t matter. The broader question is, are orthopedic surgical specialty hospitals owned by physicians, tax-exempt hospitals, or tax-paying hospitals? Is that a valid clinical business model? Is it safe? Does it meet Medicare conditions of participation? I would say that’s what that question is, because other ownership models do operate those facilities.

Dr. Glatter: You make some valid points, and I do agree on some of them. I think that, ultimately, these models of care, and certainly cost and quality, are issues. Again, it goes back to being able, in my opinion, to provide emergent care, which seems to me a very important issue.

Dr. Miller: I agree that providing emergent care is an issue. It›s an issue in any site of care. The hospital industry posits that all hospital outpatient departments (HOPDs) have emergent care. I can tell you, having worked in HOPDs (I›ve trained in them during residency), the response if something emergent happens is to either call 911 or wheel the patient down to the ER in a wheelchair or stretcher. I think that these hospital claims about emergency care coverage — these are important questions, but we should be asking them across all clinical settings and say what is the appropriate scope of care provided? What is the appropriate level of acuity and ability to provide emergent or critical care? That›s an important question regardless of ownership model across the entire industry.

Deeper Dive Into Data on Physician-Owned Hospitals

Dr. Glatter: We need to really focus on that. I’ll agree with you on that.

There was a March 2023 report from Dobson | DaVanzo. It showed that physician-owned hospitals had lower Medicaid, dual-eligible, and uncompensated care and charity care discharges than full-service acute care hospitals. Physician-owned hospitals had less than half the proportion of Medicaid discharges compared with non–physician-owned hospitals. They were also less likely to care for dual-eligible patients overall compared with non–physician-owned hospitals.

In addition, when COVID hit, the physician-owned hospitals overall — and again, there may be exceptions — were not equipped to handle these patient surges in the acute setting of a public health emergency. There was a hospital in Texas that did pivot that I’m aware of — Renaissance Hospital, which ramped up a long-term care facility to become a COVID hospital — but I think that’s the exception. I think this report raises some valid concerns; I’ll let you rebut that.

Dr. Miller: A couple of things. One, I am not aware that there’s any clear market evidence or a systematic study that shows that physician-owned hospitals had trouble responding to COVID. I don’t think that assertion has been proven. The study was funded by the hospital industry. First of all, it was not a peer-reviewed study; it was funded by an industry that paid a consulting firm. It doesn’t mean that we still shouldn’t read it, but that brings bias into question. The joke in Washington is, pick your favorite statistician or economist, and they can say what you want and have a battle of economists and statisticians.

For example, in that study, they didn’t include the entire ownership universe of physician-owned hospitals. If we go to the peer-reviewed literature, there’s a great 2015 BMJ paper showing that the Medicaid payer mix is actually the same between physician-owned hospitals vs not. The mix of patients by ethnicity — for example, think about African American patients — was the same. I would be more inclined to believe the peer-reviewed literature in BMJ as opposed to an industry-funded study that was not peer-reviewed and not independent and has methodological questions.

Dr. Glatter: Those data are 8 years old, so I’d like to see more recent data. It would be interesting, just as a follow-up to that, to see where the needle has moved — if it has, for that matter — in terms of Medicaid patients that you’re referring to.

Dr. Miller: I tend to be skeptical of all industry research, regardless of who published it, because they have an economic incentive. If they’re selecting certain age groups or excluding certain hospitals, that makes you wonder about the validity of the study. Your job as an industry-funded researcher is that, essentially, you’re being paid to look for an answer. It’s not necessarily an honest evaluation of the data.

Dr. Glatter: I want to bring up another point about the Hospital Readmissions Reduction Program (HRRP) and the data on how physician-owned hospitals compared with acute care hospitals that are non–physician-owned and have you comment on that. The Dobson | DaVanzo study called into question that physician-owned hospitals treat fewer patients who are dual-eligible, which we know.

Dr. Miller: I don’t think we do know that.

Dr. Glatter: There are data that point to that, again, looking at the studies.

Dr. Miller: I’m saying that’s a single study funded by industry as opposed to an independent, academic, peer-reviewed literature paper. That would be like saying, during the debate of the Inflation Reduction Act (IRA), that you should read the pharmaceutical industries research but take any of it at pure face value as factual. Yes, we should read it. Yes, we should evaluate it on its own merits. I think, again, appropriately, you need to be concerned when people have an economic incentive.

The question about the HRRP I’m going to take a little broader, because I think that program is unfair to the industry overall. There are many factors that drive hospital readmission. Whether Mrs Smith went home and ate potato chips and then took her Lasix, that’s very much outside of the hospital industry’s control, and there’s some evidence that the HRRP increases mortality in some patient populations.

In terms of a quality metric, it’s unfair to the industry. I think we took an operating process, internal metric for the hospital industry, turned it into a quality metric, and attached it to a financial bonus, which is an inappropriate policy decision.

Rethinking Ownership Models and Empowering Clinicians

Dr. Glatter: I agree with you on that. One thing I do want to bring up is that whether the physician-owned hospitals are subject to many of the quality measures that full-service, acute care hospitals are. That really is, I think, a broader context.

Dr. Miller: Fifty-five percent of physician-owned hospitals are full-service community hospitals, so I would say at least half the market is 100% subject to that.

Dr. Glatter: If only 50% are, that’s already an issue.

Dr. Miller: Cardiac specialty hospitals — which, as I said, nonprofit and for-profit hospital chains also operate — are also subject to the appropriate quality measures, readmissions, etc. Just because we don’t necessarily have the best quality measurement in the system in the country, it doesn’t mean that we shouldn’t allow care specialization. As I’d point out, if we’re concerned about specialty hospitals, the concern shouldn’t just be about physician-owned specialty hospitals; it should be about specialty hospitals by and large. Many health systems run cardiac specialty hospitals, cancer specialty hospitals, and orthopedic specialty hospitals. If we’re going to have a discussion about concerns there, it should be about the entire industry of specialty hospitals.

I think specialty hospitals serve an important role in society, allowing for specialization and exploiting in a positive way the volume-quality relationship. Whether those are owned by a for-profit publicly traded company, a tax-exempt facility, or physicians, I think that is an important way to have innovation and care delivery because frankly, we haven’t had much innovation in care delivery. Much of what we do in terms of how we practice clinically hasn’t really changed in the 50 years since my late father graduated from medical school. We still have rounds, we’re still taking notes, we’re still operating in the same way. Many processes are manual. We don’t have the mass production and mass customization of care that we need.

When you have a focused factory, it allows you to design care in a way that drives up quality, not just for the average patient but also the patients at the tail ends, because you have time to focus on that specific service line and that specific patient population.

Physician-owned community hospitals offer an important opportunity for a different employment model. I remember going to the dermatologist and the dermatologist was depressed, shuffling around the room, sad, and I asked him why. He said he didn’t really like his employer, and I said, “Why don’t you pick another one?” He’s like, “There are only two large health systems I can work for. They all have the same clinical practice environment and functionally the same value.”

Physicians are increasingly burned out. They face monopsony power in who purchases their labor. They have little control. They don’t want to go through five committees, seven administrators, and attend 25 meetings just to change a single small process in clinical operations. If you’re an owner operator, you have a much better ability to do it.

Frankly, when many facilities do well now, when they do well clinically and do well financially, who benefits? The hospital administration and the hospital executives. The doctors aren’t benefiting. The nurses aren’t benefiting. The CNA is not benefiting. The secretary is not benefiting. The custodian is not benefiting. Shouldn’t the workers have a right to own and operate the business and do well when the business does well serving the community? That puts me in the weird space of agreeing with both conservatives and progressives.

Dr. Glatter: I agree with you. I think an ownership stake is always attractive. It helps with retention of employed persons. There›s no question that, when they have a stake, when they have skin in the game, they feel more empowered. I will not argue with you about that.

Dr. Miller: We don’t have business models where workers have that option in healthcare. Like the National Academy of Medicine said, one of the key drivers of burnout is the externalization of the locus of control over clinical practice, and the current business operating models guarantee an externalization of the locus of control over clinical practice.

If you actually look at the recent American Medical Association (AMA) meeting, there was a resolution to ban the corporate practice of medicine. They wanted to go more toward the legal professions model where only physicians can own and operate care delivery.

Dr. Glatter: Well, I think the shift is certainly something that the AMA would like and physicians collectively would agree with. Having a better lifestyle and being able to have control are factors in burnout.

Dr. Miller: It’s not just doctors. I think nurses want a better lifestyle. The nurses are treated as interchangeable lines on a spreadsheet. The nurses are an integral part of our clinical team. Why don’t we work together as a clinical unit to build a better delivery system? What better way to do that than to have clinicians in charge of it, right?

My favorite bakery that’s about 30 minutes away is owned by a baker. It is not owned by a large tax-exempt corporation. It’s owned by an owner operator who takes pride in their work. I think that is something that the profession would do well to return to. When I was a resident, one of my colleagues was already planning their retirement. That’s how depressed they were.

I went into medicine to actually care for patients. I think that we can make the world a better place for our patients. What that means is not only treating them with drugs and devices, but also creating a delivery system where they don’t have to wander from lobby to lobby in a 200,000 square-foot facility, wait in line for hours on end, get bills 6 months later, and fill out endless paper forms over and over again.

All of these basic processes in healthcare delivery that are broken could have and should have been fixed — and have been fixed in almost every other industry. I had to replace one of my car tires because I had a flat tire. The local tire shop has an app, and it sends me SMS text messages telling me when my appointment is and when my car is ready. We have solved all of these problems in many other businesses.

We have not solved them in healthcare delivery because, one, we have massive monopolies that are raising prices, have lower quality, and deliver a crappy patient experience, and we have also subjugated the clinical worker into a corporate automaton. We are functionally drones. We don’t have the agency and the authority to improve clinical operations anymore. It’s really depressing, and we should have that option again.

I trust my doctor. I trust the nurses that I work with, and I would like them to help make clinical decisions in a financially responsible and a sensible operational manner. We need to empower our workforce in order to do that so we can recapture the value of what it means to be a clinician again.

The current model of corporate employment: massive scale, more administrators, more processes, more emails, more meetings, more PowerPoint decks, more federal subsidies. The hospital industry has choices. It can improve clinical operations. It can show up in Washington and lobby for increased subsidies. It can invest in the market and not pay taxes for the tax-exempt facilities. Obviously, it makes the logical choices as an economic actor to show up, lobby for increased subsidies, and then also invest in the stock market.

Improving clinical operations is hard. It hasn’t happened. The Bureau of Labor Statistics shows that the private community hospital industry has had flat labor productivity growth, on average, for the past 25 years, and for some years it even declined. This is totally atypical across the economy.

We have failed our clinicians, and most importantly, we have failed our patients. I’ve been sick. My relatives have been sick, waiting hours, not able to get appointments, and redoing forms. It’s a total disaster. It’s time and reasonable to try an alternative ownership and operating model. There are obviously problems. The problems can and should be addressed, but it doesn’t mean that we should have a statutory prohibition on professionals owning and operating their own business.

Dr. Glatter: There was a report that $500 million was saved by limiting or banning or putting a moratorium on physician-owned hospitals by the Congressional Budget Office.

Dr. Miller: Yes, I’m very aware of those data. I’d say that the CBO also is off by 50% on the estimation of the implementation of the Part D program. They overestimated the Affordable Care Act market enrollment by over 10 million people — again, around 50%. They also estimated that the CMS Innovation Center initially would be a savings. Now they’ve re-estimated it as a 10-year expenditure and it has actually cost the taxpayers money.

The CBO is not transparent about what its assumptions are or its analysis and methods. As a researcher, we have to publish our information. It has to go through peer review. I want to know what goes into that $500 million figure — what the assumptions are and what the model is. It’s hard to comment without knowing how they came up with it.

Dr. Glatter: The points you make are very valid. Physicians and nurses want a better lifestyle.

Dr. Miller: It’s not even a better lifestyle. It’s about having a say in how clinical operations work and helping make them better. We want the delivery system to work better. This is an opportunity for us to do so.

Dr. Glatter: That translates into technology: obviously, generative artificial intelligence (AI) coming into the forefront, as we know, and changing care delivery models as you’re referring to, which is going to happen. It’s going to be a slow process. I think that the evolution is happening and will happen, as you accurately described.

Dr. Miller: The other thing that’s different now vs 20 years ago is that managed care is here, there, and everywhere, as Dr Seuss would say. You have utilization review and prior authorization, which I’ve experienced as a patient and a physician, and boy, is it not a fun process. There’s a large amount of friction that needs to be improved. If we’re worried about induced demand or inappropriate utilization, we have managed care right there to help police bad behavior.

Reforming Healthcare Systems and Restoring Patient-Centric Focus

Dr. Glatter: If you were to come up with, say, three bullet points of how we can work our way out of this current morass of where our healthcare systems exist, where do you see the solutions or how can we make and effect change?

Dr. Miller: I’d say there are a couple of things. One is, let business models compete fairly on an equal playing field. Let the physician-owned hospital compete with the tax-exempt hospital and the nonprofit hospital. Put them on an equal playing field. We have things like 340B, which favors tax-exempt hospitals. For-profit or tax-paying hospitals are not able to participate in that. That doesn’t make any sense just from a public policy perspective. Tax-paying hospitals and physician-owned hospitals pay taxes on investments, but tax-exempt hospitals don’t. I think, in public policy, we need to equalize the playing field between business models. Let the best business model win.

The other thing we need to do is to encourage the adoption of technology. The physician will eventually be an arbiter of tech-driven or AI-driven tools. In fact, at some point, the standard of care might be to use those tools. Not using those tools would be seen as negligence. If you think about placing a jugular or central venous catheter, to not use ultrasound would be considered insane. Thirty years ago, to use ultrasound would be considered novel. I think technology and AI will get us to that point of helping make care more efficient and more customized.

Those are the two biggest interventions, I would say. Third, every time we have a conversation in public policy, we need to remember what it is to be a patient. The decision should be driven not around any one industry’s profitability, but what it is to be a patient and how we can make that experience less burdensome, less expensive, or in plain English, suck less.

Dr. Glatter: Safety net hospitals and critical access hospitals are part of this discussion that, yes, we want everything to, in an ideal world, function more efficiently and effectively, with less cost and less red tape. The safety net of our nation is struggling.

Dr. Miller: I 100% agree. The Cook County hospitals of the world are deserving of our support and, frankly, our gratitude. Facilities like that have huge burdens of patients with Medicaid. We also still have millions of uninsured patients. The neighborhoods that they serve are also poorer. I think facilities like that are deserving of public support.

I also think we need to clearly define what those hospitals are. One of the challenges I’ve realized as I waded into this space is that market definitions of what a service market is for a hospital, its specialty type or what a safety net hospital is need to be more clearly defined because those facilities 100% are deserving of our support. We just need to be clear about what they are.

Regarding critical access hospitals, when you practice in a rural area, you have to think differently about care delivery. I’d say many of the rural systems are highly creative in how they structure clinical operations. Before the public health emergency, during the COVID pandemic, when we had a massive change in telehealth, rural hospitals were using — within the very narrow confines — as much telehealth as they could and should.

Rural hospitals also make greater use of nurse practitioners (NPs) and physician assistants (PAs). For many of the specialty services, I remember, your first call was an NP or a PA because the physician was downstairs doing procedures. They’d come up and assess the patient before the procedure, but most of your consult questions were answered by the NP or PA. I’m not saying that’s the model we should use nationwide, but that rural systems are highly innovative and creative; they’re deserving of our time, attention, and support, and frankly, we can learn from them.

Dr. Glatter: I want to thank you for your time and your expertise in this area. We’ll see how the congressional hearings affect the industry as a whole, how the needle moves, and whether the ban or moratorium on physician-owned hospitals continues to exist going forward.

Dr. Miller: I appreciate you having me. The hospital industry is one of the most important industries for health care. This is a time of inflection, right? We need to go back to the value of what it means to be a clinician and serve patients. Hospitals need to reorient themselves around that core concern. How do we help support clinicians — doctors, nurses, pharmacists, whomever it is — in serving patients? Hospitals have become too corporate, so I think that this is an expected pushback.

Dr. Glatter: Again, I want to thank you for your time. This was a very important discussion. Thank you for your expertise.



Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. He disclosed no relevant financial relationships.Brian J. Miller, MD, MBA, MPH, is a hospitalist and an assistant professor of medicine at the Johns Hopkins University School of Medicine. He is also a nonresident fellow at the American Enterprise Institute. From 2014 to 2017, Dr. Miller worked at four federal regulatory agencies: Federal Trade Commission (FTC), Federal Communications Commission (FCC), Centers for Medicare & Medicaid Services (CMS), and the Food & Drug Administration (FDA). Dr. Miller disclosed ties with the Medicare Payment Advisory Commission.
 

A version of this article appeared on Medscape.com.

This discussion was recorded on November 16, 2023. This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. Joining me today is Dr. Brian J. Miller, a hospitalist with Johns Hopkins University School of Medicine and a health policy expert, to discuss the current and renewed interest in physician-owned hospitals.

Welcome, Dr. Miller. It’s a pleasure to have you join me today.

Brian J. Miller, MD, MBA, MPH: Thank you for having me.

History and Controversies Surrounding Physician-Owned Hospitals

Dr. Glatter: I want to start off by having you describe the history associated with the moratorium on new physician-owned hospitals in 2010 that’s related ultimately to the Affordable Care Act, but also, the current and renewed media interest in physician-owned hospitals that’s linked to recent congressional hearings last month.

Dr. Miller: Thank you. I should note that my views are my own and don’t represent those of Hopkins or the American Enterprise Institute, where I’m a nonresident fellow nor the Medicare Payment Advisory Commission, of which I’m a Commissioner.

The story about physician-owned hospitals is an interesting one. Hospitals turned into health systems in the 1980s and 1990s, and physicians started to shift purely from an independent model into a more organized group practice or employed model. Physicians realized that they wanted an alternative operating arrangement. You want a choice of how you practice and what your employment is. And as community hospitals started to buy physicians and also establish their own physician groups de novo, physicians opened physician-owned hospitals.

Physician-owned hospitals fell into a couple of buckets. One is what we call community hospitals, or what the antitrust lawyers would call general acute care hospitals: those offering emergency room (ER) services, labor and delivery, primary care, general surgery — the whole regular gamut, except that some of the owners were physicians.

The other half of the marketplace ended up being specialty hospitals: those built around a specific medical specialty and series of procedures and chronic care. For example, cardiac hospitals often do CABG, TAVR, maybe abdominal aortic aneurysm (triple A) repairs, and they have cardiology clinics, cath labs, a cardiac intensive care unit (ICU), ER, etc. There were also orthopedic surgical specialty hospitals, which were sort of like an ambulatory surgery center (ASC) plus several beds. Then there were general surgical specialty hospitals. At one point, there were some women’s health–focused specialty hospitals.

The hospital industry, of course, as you can understand, didn’t exactly like this. They had a series of concerns about what we would historically call cherry-picking or lemon-dropping of patients. They were worried that physician-owned facilities didn’t want to serve public payer patients, and there was a whole series of reports and investigations.

Around the time the Affordable Care Act passed, the hospital industry had many concerns about physician-owned specialty hospitals, and there was a moratorium as part of the 2003 Medicare Modernization Act. As part of the bargaining over the hospital industry support for the Affordable Care Act, they traded their support for, among other things, their number one priority, which is a statutory prohibition on new or expanded physician-owned hospitals from participating in Medicare. That included both physician-owned community hospitals and physician-owned specialty hospitals.

Dr. Glatter: I guess the main interest is that, when physicians have an ownership or a stake in the hospital, this is what the Stark laws obviously were aimed at. That was part of the impetus to prevent physicians from referring patients where they had an ownership stake. Certainly, hospitals can be owned by attorneys and nonprofit organizations, and certainly, ASCs can be owned by physicians. There is an ongoing issue in terms of physicians not being able to have an ownership stake. In terms of equity ownership, we know that certain other models allow this, but basically, it sounds like this is an issue with Medicare. That seems to be the crux of it, correct?

Dr. Miller: Yes. I would also add that it’s interesting when we look at other professions. When we look at lawyers, nonlawyers are actually not allowed to own an equity stake in a law practice. In many other professions, you either have corporate ownership or professional ownership, or the alternative is you have only professional ownership. I would say the hospital industry is one of the few areas where professional ownership not only is not allowed, but also is statutorily prohibited functionally through the Medicare program.

Unveiling the Dynamics of Hospital Ownership

Dr. Glatter: A recent study done by two PhDs looked at 2019 data on 20 of the most expensive diagnosis-related groups (DRGs). It examined the cost savings, and we’re talking over $1 billion in expenditures when you look at the data from general acute care hospitals vs physician-owned hospitals. This is what appears to me to be a key driver of the push to loosen restrictions on physician-owned hospitals. Isn’t that correct?

Dr. Miller: I would say that’s one of many components. There’s more history to this issue. I remember sitting at a think tank talking to someone several years ago about hospital consolidation as an issue. We went through the usual levers that us policy wonks go through. We talked about antitrust enforcement, certificate of need, rising hospital costs from consolidation, lower quality (or at least no quality gains, as shown by a New England Journal of Medicine study), and decrements in patient experience that result from the diseconomies of scale. They sort of pooh-poohed many of the policy ideas. They basically said that there was no hope for hospital consolidation as an issue.

Well, what about physician ownership? I started with my research team to comb through the literature and found a variety of studies — some of which were sort of entertaining, because they’d do things like study physician-owned specialty hospitals, nonprofit-owned specialty hospitals, and for-profit specialty hospitals and compare them with nonprofit or for-profit community hospitals, and then say physician-owned hospitals that were specialty were bad.

They mixed ownership and service markets right there in so many ways, I’m not sure where to start. My team did a systematic review of around 30 years of research, looking at the evidence base in this space. We found a couple of things.

We found that physician-owned community hospitals did not have a cost or quality difference, meaning that there was no definitive evidence that the physician-owned community hospitals were cheaper based on historical evidence, which was very old. That means there’s not specific harm from them. When you permit market entry for community hospitals, that promotes competition, which results in lower prices and higher quality.

Then we also looked at the specialty hospital markets — surgical specialty hospitals, orthopedic surgical specialty hospitals, and cardiac hospitals. We noted for cardiac hospitals, there wasn’t clear evidence about cost savings, but there was definitive evidence of higher quality, from things like 30-day mortality for significant procedures like treatment of acute MI, triple A repair, stuff like that.

For orthopedic surgical specialty hospitals, we noted lower costs and higher quality, which again fits with operationally what we would know. If you have a facility that’s doing 20 total hips a day, you’re creating a focused factory. Just like if you think about it for interventional cardiology, your boards have a minimum number of procedures that you have to do to stay certified because we know about the volume-quality relationship.

Then we looked at general surgical specialty hospitals. There wasn’t enough evidence to make a conclusive thought about costs, and there was a clear trend toward higher quality. I would say this recent study is important, but there is a whole bunch of other literature out there, too.

Exploring the Scope of Emergency Care in Physician-Owned Hospitals

Dr. Glatter: Certainly, your colleague Wang from Johns Hopkins has done important research in this sector. The paper, “Reconsidering the Ban on Physician-Owned Hospitals to Combat Consolidation,” by you and several colleagues, mentions and highlights the issues that you just described. I understand that it’s going to be published in the NYU Journal of Legislation and Public Policy.

One thing I want to bring up — and this is an important issue — is that the risk for patients has been talked about by the American Hospital Association and the Federation of American Hospitals, in terms of limited or no emergency services at such physician-owned hospitals and having to call 911 when patients need emergent care or stabilization. That’s been the rebuttal, along with an Office of Inspector General (OIG) report from 2008. Almost, I guess, three quarters of the patients that needed emergent care got this at publicly funded hospitals.

Dr. Miller: I’m familiar with the argument about emergency care. If you actually go and look at it, it differs by specialty market. Physician-owned community hospitals have ERs because that’s how they get their business. If you are running a hospital medicine floor, a general surgical specialty floor, you have a labor delivery unit, a primary care clinic, and a cardiology clinic. You have all the things that all the other hospitals have. The physician-owned community hospitals almost uniformly have an ER.

When you look at the physician-owned specialty hospitals, it’s a little more granular. If you look at the cardiac hospitals, they have ERs. They also have cardiac ICUs, operating rooms, etc. The area where the hospital industry had concerns — which I think is valid to point out — is that physician-owned orthopedic surgical specialty hospitals don’t have ERs. But this makes sense because of what that hospital functionally is: a factory for whatever the scope of procedures is, be it joint replacements or shoulder arthroscopy. The orthopedic surgical specialty hospital is like an ASC plus several hospital beds. Many of those did not have ERs because clinically it didn’t make sense.

What’s interesting, though, is that the hospital industry also operates specialty hospitals. If you go into many of the large systems, they have cardiac specialty hospitals and cancer specialty hospitals. I would say that some of them have ERs, as they appropriately should, and some of those specialty hospitals do not. They might have a community hospital down the street that’s part of that health system that has an ER, but some of the specialty hospitals don’t necessarily have a dedicated ER.

I agree, that’s a valid concern. I would say, though, the question is, what are the scope of services in that hospital? Is an ER required? Community hospitals should have ERs. It makes sense also for a cardiac hospital to have one. If you’re running a total joint replacement factory, it might not make clinical sense.

Dr. Glatter: The patients who are treated at that hospital, if they do have emergent conditions, need to have board-certified emergency physicians treating them, in my view because I’m an ER physician. Having surgeons that are not emergency physicians staff a department at a specialty orthopedic hospital or, say, a cancer hospital is not acceptable from my standpoint. That›s my opinion and recommendation, coming from emergency medicine.

Dr. Miller: I would say that anesthesiologists are actually highly qualified in critical care. The question is about clinical decompensation; if you’re doing a procedure, you have an anesthesiologist right there who is capable of critical care. The function of the ER is to either serve as a window into the hospital for patient volume or to serve as a referral for emergent complaints.

Dr. Glatter: An anesthesiologist — I’ll take issue with that — does not have the training of an emergency physician in terms of scope of practice.

Dr. Miller: My anesthesiology colleagues would probably disagree for managing an emergency during an operating room case.

Dr. Glatter: Fair enough, but I think in the general sense. The other issue is that, in terms of emergent responses to patients that decompensate, when you have to transfer a patient, that violates Medicare requirements. How is that even a valid issue or argument if you’re going to have to transfer a patient from your specialty hospital? That happens. Again, I know that you’re saying these hospitals are completely independent and can function, stabilize patients, and treat emergencies, but that’s not the reality across the country, in my opinion.

Dr. Miller: I don’t think that’s the case for the physician-owned specialty cardiac hospitals, for starters. Many of those have ICUs in addition to operating rooms as a matter of routine in addition to ERs. I don’t think that’s the case for physician-owned community hospitals, which have ERs, ICUs, medicine floors, and surgical floors. Physician-owned community hospitals are around half the market. Of that remaining market, a significant percentage are cardiac hospitals. If you’re taking an issue with orthopedic surgical specialty hospitals, that’s a clinical operational question that can and should be answered.

I’d also posit that the nonprofit and for-profit hospital industries also operate specialty hospitals. Any of these questions, we shouldn’t just be asking about physician-owned facilities; we should be asking about them across ownership types, because we’re talking about scope of service and quality and safety. The ownership in that case doesn’t matter. The broader question is, are orthopedic surgical specialty hospitals owned by physicians, tax-exempt hospitals, or tax-paying hospitals? Is that a valid clinical business model? Is it safe? Does it meet Medicare conditions of participation? I would say that’s what that question is, because other ownership models do operate those facilities.

Dr. Glatter: You make some valid points, and I do agree on some of them. I think that, ultimately, these models of care, and certainly cost and quality, are issues. Again, it goes back to being able, in my opinion, to provide emergent care, which seems to me a very important issue.

Dr. Miller: I agree that providing emergent care is an issue. It›s an issue in any site of care. The hospital industry posits that all hospital outpatient departments (HOPDs) have emergent care. I can tell you, having worked in HOPDs (I›ve trained in them during residency), the response if something emergent happens is to either call 911 or wheel the patient down to the ER in a wheelchair or stretcher. I think that these hospital claims about emergency care coverage — these are important questions, but we should be asking them across all clinical settings and say what is the appropriate scope of care provided? What is the appropriate level of acuity and ability to provide emergent or critical care? That›s an important question regardless of ownership model across the entire industry.

Deeper Dive Into Data on Physician-Owned Hospitals

Dr. Glatter: We need to really focus on that. I’ll agree with you on that.

There was a March 2023 report from Dobson | DaVanzo. It showed that physician-owned hospitals had lower Medicaid, dual-eligible, and uncompensated care and charity care discharges than full-service acute care hospitals. Physician-owned hospitals had less than half the proportion of Medicaid discharges compared with non–physician-owned hospitals. They were also less likely to care for dual-eligible patients overall compared with non–physician-owned hospitals.

In addition, when COVID hit, the physician-owned hospitals overall — and again, there may be exceptions — were not equipped to handle these patient surges in the acute setting of a public health emergency. There was a hospital in Texas that did pivot that I’m aware of — Renaissance Hospital, which ramped up a long-term care facility to become a COVID hospital — but I think that’s the exception. I think this report raises some valid concerns; I’ll let you rebut that.

Dr. Miller: A couple of things. One, I am not aware that there’s any clear market evidence or a systematic study that shows that physician-owned hospitals had trouble responding to COVID. I don’t think that assertion has been proven. The study was funded by the hospital industry. First of all, it was not a peer-reviewed study; it was funded by an industry that paid a consulting firm. It doesn’t mean that we still shouldn’t read it, but that brings bias into question. The joke in Washington is, pick your favorite statistician or economist, and they can say what you want and have a battle of economists and statisticians.

For example, in that study, they didn’t include the entire ownership universe of physician-owned hospitals. If we go to the peer-reviewed literature, there’s a great 2015 BMJ paper showing that the Medicaid payer mix is actually the same between physician-owned hospitals vs not. The mix of patients by ethnicity — for example, think about African American patients — was the same. I would be more inclined to believe the peer-reviewed literature in BMJ as opposed to an industry-funded study that was not peer-reviewed and not independent and has methodological questions.

Dr. Glatter: Those data are 8 years old, so I’d like to see more recent data. It would be interesting, just as a follow-up to that, to see where the needle has moved — if it has, for that matter — in terms of Medicaid patients that you’re referring to.

Dr. Miller: I tend to be skeptical of all industry research, regardless of who published it, because they have an economic incentive. If they’re selecting certain age groups or excluding certain hospitals, that makes you wonder about the validity of the study. Your job as an industry-funded researcher is that, essentially, you’re being paid to look for an answer. It’s not necessarily an honest evaluation of the data.

Dr. Glatter: I want to bring up another point about the Hospital Readmissions Reduction Program (HRRP) and the data on how physician-owned hospitals compared with acute care hospitals that are non–physician-owned and have you comment on that. The Dobson | DaVanzo study called into question that physician-owned hospitals treat fewer patients who are dual-eligible, which we know.

Dr. Miller: I don’t think we do know that.

Dr. Glatter: There are data that point to that, again, looking at the studies.

Dr. Miller: I’m saying that’s a single study funded by industry as opposed to an independent, academic, peer-reviewed literature paper. That would be like saying, during the debate of the Inflation Reduction Act (IRA), that you should read the pharmaceutical industries research but take any of it at pure face value as factual. Yes, we should read it. Yes, we should evaluate it on its own merits. I think, again, appropriately, you need to be concerned when people have an economic incentive.

The question about the HRRP I’m going to take a little broader, because I think that program is unfair to the industry overall. There are many factors that drive hospital readmission. Whether Mrs Smith went home and ate potato chips and then took her Lasix, that’s very much outside of the hospital industry’s control, and there’s some evidence that the HRRP increases mortality in some patient populations.

In terms of a quality metric, it’s unfair to the industry. I think we took an operating process, internal metric for the hospital industry, turned it into a quality metric, and attached it to a financial bonus, which is an inappropriate policy decision.

Rethinking Ownership Models and Empowering Clinicians

Dr. Glatter: I agree with you on that. One thing I do want to bring up is that whether the physician-owned hospitals are subject to many of the quality measures that full-service, acute care hospitals are. That really is, I think, a broader context.

Dr. Miller: Fifty-five percent of physician-owned hospitals are full-service community hospitals, so I would say at least half the market is 100% subject to that.

Dr. Glatter: If only 50% are, that’s already an issue.

Dr. Miller: Cardiac specialty hospitals — which, as I said, nonprofit and for-profit hospital chains also operate — are also subject to the appropriate quality measures, readmissions, etc. Just because we don’t necessarily have the best quality measurement in the system in the country, it doesn’t mean that we shouldn’t allow care specialization. As I’d point out, if we’re concerned about specialty hospitals, the concern shouldn’t just be about physician-owned specialty hospitals; it should be about specialty hospitals by and large. Many health systems run cardiac specialty hospitals, cancer specialty hospitals, and orthopedic specialty hospitals. If we’re going to have a discussion about concerns there, it should be about the entire industry of specialty hospitals.

I think specialty hospitals serve an important role in society, allowing for specialization and exploiting in a positive way the volume-quality relationship. Whether those are owned by a for-profit publicly traded company, a tax-exempt facility, or physicians, I think that is an important way to have innovation and care delivery because frankly, we haven’t had much innovation in care delivery. Much of what we do in terms of how we practice clinically hasn’t really changed in the 50 years since my late father graduated from medical school. We still have rounds, we’re still taking notes, we’re still operating in the same way. Many processes are manual. We don’t have the mass production and mass customization of care that we need.

When you have a focused factory, it allows you to design care in a way that drives up quality, not just for the average patient but also the patients at the tail ends, because you have time to focus on that specific service line and that specific patient population.

Physician-owned community hospitals offer an important opportunity for a different employment model. I remember going to the dermatologist and the dermatologist was depressed, shuffling around the room, sad, and I asked him why. He said he didn’t really like his employer, and I said, “Why don’t you pick another one?” He’s like, “There are only two large health systems I can work for. They all have the same clinical practice environment and functionally the same value.”

Physicians are increasingly burned out. They face monopsony power in who purchases their labor. They have little control. They don’t want to go through five committees, seven administrators, and attend 25 meetings just to change a single small process in clinical operations. If you’re an owner operator, you have a much better ability to do it.

Frankly, when many facilities do well now, when they do well clinically and do well financially, who benefits? The hospital administration and the hospital executives. The doctors aren’t benefiting. The nurses aren’t benefiting. The CNA is not benefiting. The secretary is not benefiting. The custodian is not benefiting. Shouldn’t the workers have a right to own and operate the business and do well when the business does well serving the community? That puts me in the weird space of agreeing with both conservatives and progressives.

Dr. Glatter: I agree with you. I think an ownership stake is always attractive. It helps with retention of employed persons. There›s no question that, when they have a stake, when they have skin in the game, they feel more empowered. I will not argue with you about that.

Dr. Miller: We don’t have business models where workers have that option in healthcare. Like the National Academy of Medicine said, one of the key drivers of burnout is the externalization of the locus of control over clinical practice, and the current business operating models guarantee an externalization of the locus of control over clinical practice.

If you actually look at the recent American Medical Association (AMA) meeting, there was a resolution to ban the corporate practice of medicine. They wanted to go more toward the legal professions model where only physicians can own and operate care delivery.

Dr. Glatter: Well, I think the shift is certainly something that the AMA would like and physicians collectively would agree with. Having a better lifestyle and being able to have control are factors in burnout.

Dr. Miller: It’s not just doctors. I think nurses want a better lifestyle. The nurses are treated as interchangeable lines on a spreadsheet. The nurses are an integral part of our clinical team. Why don’t we work together as a clinical unit to build a better delivery system? What better way to do that than to have clinicians in charge of it, right?

My favorite bakery that’s about 30 minutes away is owned by a baker. It is not owned by a large tax-exempt corporation. It’s owned by an owner operator who takes pride in their work. I think that is something that the profession would do well to return to. When I was a resident, one of my colleagues was already planning their retirement. That’s how depressed they were.

I went into medicine to actually care for patients. I think that we can make the world a better place for our patients. What that means is not only treating them with drugs and devices, but also creating a delivery system where they don’t have to wander from lobby to lobby in a 200,000 square-foot facility, wait in line for hours on end, get bills 6 months later, and fill out endless paper forms over and over again.

All of these basic processes in healthcare delivery that are broken could have and should have been fixed — and have been fixed in almost every other industry. I had to replace one of my car tires because I had a flat tire. The local tire shop has an app, and it sends me SMS text messages telling me when my appointment is and when my car is ready. We have solved all of these problems in many other businesses.

We have not solved them in healthcare delivery because, one, we have massive monopolies that are raising prices, have lower quality, and deliver a crappy patient experience, and we have also subjugated the clinical worker into a corporate automaton. We are functionally drones. We don’t have the agency and the authority to improve clinical operations anymore. It’s really depressing, and we should have that option again.

I trust my doctor. I trust the nurses that I work with, and I would like them to help make clinical decisions in a financially responsible and a sensible operational manner. We need to empower our workforce in order to do that so we can recapture the value of what it means to be a clinician again.

The current model of corporate employment: massive scale, more administrators, more processes, more emails, more meetings, more PowerPoint decks, more federal subsidies. The hospital industry has choices. It can improve clinical operations. It can show up in Washington and lobby for increased subsidies. It can invest in the market and not pay taxes for the tax-exempt facilities. Obviously, it makes the logical choices as an economic actor to show up, lobby for increased subsidies, and then also invest in the stock market.

Improving clinical operations is hard. It hasn’t happened. The Bureau of Labor Statistics shows that the private community hospital industry has had flat labor productivity growth, on average, for the past 25 years, and for some years it even declined. This is totally atypical across the economy.

We have failed our clinicians, and most importantly, we have failed our patients. I’ve been sick. My relatives have been sick, waiting hours, not able to get appointments, and redoing forms. It’s a total disaster. It’s time and reasonable to try an alternative ownership and operating model. There are obviously problems. The problems can and should be addressed, but it doesn’t mean that we should have a statutory prohibition on professionals owning and operating their own business.

Dr. Glatter: There was a report that $500 million was saved by limiting or banning or putting a moratorium on physician-owned hospitals by the Congressional Budget Office.

Dr. Miller: Yes, I’m very aware of those data. I’d say that the CBO also is off by 50% on the estimation of the implementation of the Part D program. They overestimated the Affordable Care Act market enrollment by over 10 million people — again, around 50%. They also estimated that the CMS Innovation Center initially would be a savings. Now they’ve re-estimated it as a 10-year expenditure and it has actually cost the taxpayers money.

The CBO is not transparent about what its assumptions are or its analysis and methods. As a researcher, we have to publish our information. It has to go through peer review. I want to know what goes into that $500 million figure — what the assumptions are and what the model is. It’s hard to comment without knowing how they came up with it.

Dr. Glatter: The points you make are very valid. Physicians and nurses want a better lifestyle.

Dr. Miller: It’s not even a better lifestyle. It’s about having a say in how clinical operations work and helping make them better. We want the delivery system to work better. This is an opportunity for us to do so.

Dr. Glatter: That translates into technology: obviously, generative artificial intelligence (AI) coming into the forefront, as we know, and changing care delivery models as you’re referring to, which is going to happen. It’s going to be a slow process. I think that the evolution is happening and will happen, as you accurately described.

Dr. Miller: The other thing that’s different now vs 20 years ago is that managed care is here, there, and everywhere, as Dr Seuss would say. You have utilization review and prior authorization, which I’ve experienced as a patient and a physician, and boy, is it not a fun process. There’s a large amount of friction that needs to be improved. If we’re worried about induced demand or inappropriate utilization, we have managed care right there to help police bad behavior.

Reforming Healthcare Systems and Restoring Patient-Centric Focus

Dr. Glatter: If you were to come up with, say, three bullet points of how we can work our way out of this current morass of where our healthcare systems exist, where do you see the solutions or how can we make and effect change?

Dr. Miller: I’d say there are a couple of things. One is, let business models compete fairly on an equal playing field. Let the physician-owned hospital compete with the tax-exempt hospital and the nonprofit hospital. Put them on an equal playing field. We have things like 340B, which favors tax-exempt hospitals. For-profit or tax-paying hospitals are not able to participate in that. That doesn’t make any sense just from a public policy perspective. Tax-paying hospitals and physician-owned hospitals pay taxes on investments, but tax-exempt hospitals don’t. I think, in public policy, we need to equalize the playing field between business models. Let the best business model win.

The other thing we need to do is to encourage the adoption of technology. The physician will eventually be an arbiter of tech-driven or AI-driven tools. In fact, at some point, the standard of care might be to use those tools. Not using those tools would be seen as negligence. If you think about placing a jugular or central venous catheter, to not use ultrasound would be considered insane. Thirty years ago, to use ultrasound would be considered novel. I think technology and AI will get us to that point of helping make care more efficient and more customized.

Those are the two biggest interventions, I would say. Third, every time we have a conversation in public policy, we need to remember what it is to be a patient. The decision should be driven not around any one industry’s profitability, but what it is to be a patient and how we can make that experience less burdensome, less expensive, or in plain English, suck less.

Dr. Glatter: Safety net hospitals and critical access hospitals are part of this discussion that, yes, we want everything to, in an ideal world, function more efficiently and effectively, with less cost and less red tape. The safety net of our nation is struggling.

Dr. Miller: I 100% agree. The Cook County hospitals of the world are deserving of our support and, frankly, our gratitude. Facilities like that have huge burdens of patients with Medicaid. We also still have millions of uninsured patients. The neighborhoods that they serve are also poorer. I think facilities like that are deserving of public support.

I also think we need to clearly define what those hospitals are. One of the challenges I’ve realized as I waded into this space is that market definitions of what a service market is for a hospital, its specialty type or what a safety net hospital is need to be more clearly defined because those facilities 100% are deserving of our support. We just need to be clear about what they are.

Regarding critical access hospitals, when you practice in a rural area, you have to think differently about care delivery. I’d say many of the rural systems are highly creative in how they structure clinical operations. Before the public health emergency, during the COVID pandemic, when we had a massive change in telehealth, rural hospitals were using — within the very narrow confines — as much telehealth as they could and should.

Rural hospitals also make greater use of nurse practitioners (NPs) and physician assistants (PAs). For many of the specialty services, I remember, your first call was an NP or a PA because the physician was downstairs doing procedures. They’d come up and assess the patient before the procedure, but most of your consult questions were answered by the NP or PA. I’m not saying that’s the model we should use nationwide, but that rural systems are highly innovative and creative; they’re deserving of our time, attention, and support, and frankly, we can learn from them.

Dr. Glatter: I want to thank you for your time and your expertise in this area. We’ll see how the congressional hearings affect the industry as a whole, how the needle moves, and whether the ban or moratorium on physician-owned hospitals continues to exist going forward.

Dr. Miller: I appreciate you having me. The hospital industry is one of the most important industries for health care. This is a time of inflection, right? We need to go back to the value of what it means to be a clinician and serve patients. Hospitals need to reorient themselves around that core concern. How do we help support clinicians — doctors, nurses, pharmacists, whomever it is — in serving patients? Hospitals have become too corporate, so I think that this is an expected pushback.

Dr. Glatter: Again, I want to thank you for your time. This was a very important discussion. Thank you for your expertise.



Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. He disclosed no relevant financial relationships.Brian J. Miller, MD, MBA, MPH, is a hospitalist and an assistant professor of medicine at the Johns Hopkins University School of Medicine. He is also a nonresident fellow at the American Enterprise Institute. From 2014 to 2017, Dr. Miller worked at four federal regulatory agencies: Federal Trade Commission (FTC), Federal Communications Commission (FCC), Centers for Medicare & Medicaid Services (CMS), and the Food & Drug Administration (FDA). Dr. Miller disclosed ties with the Medicare Payment Advisory Commission.
 

A version of this article appeared on Medscape.com.

This discussion was recorded on November 16, 2023. This transcript has been edited for clarity.

Robert D. Glatter, MD: Welcome. I’m Dr. Robert Glatter, medical advisor for Medscape Emergency Medicine. Joining me today is Dr. Brian J. Miller, a hospitalist with Johns Hopkins University School of Medicine and a health policy expert, to discuss the current and renewed interest in physician-owned hospitals.

Welcome, Dr. Miller. It’s a pleasure to have you join me today.

Brian J. Miller, MD, MBA, MPH: Thank you for having me.

History and Controversies Surrounding Physician-Owned Hospitals

Dr. Glatter: I want to start off by having you describe the history associated with the moratorium on new physician-owned hospitals in 2010 that’s related ultimately to the Affordable Care Act, but also, the current and renewed media interest in physician-owned hospitals that’s linked to recent congressional hearings last month.

Dr. Miller: Thank you. I should note that my views are my own and don’t represent those of Hopkins or the American Enterprise Institute, where I’m a nonresident fellow nor the Medicare Payment Advisory Commission, of which I’m a Commissioner.

The story about physician-owned hospitals is an interesting one. Hospitals turned into health systems in the 1980s and 1990s, and physicians started to shift purely from an independent model into a more organized group practice or employed model. Physicians realized that they wanted an alternative operating arrangement. You want a choice of how you practice and what your employment is. And as community hospitals started to buy physicians and also establish their own physician groups de novo, physicians opened physician-owned hospitals.

Physician-owned hospitals fell into a couple of buckets. One is what we call community hospitals, or what the antitrust lawyers would call general acute care hospitals: those offering emergency room (ER) services, labor and delivery, primary care, general surgery — the whole regular gamut, except that some of the owners were physicians.

The other half of the marketplace ended up being specialty hospitals: those built around a specific medical specialty and series of procedures and chronic care. For example, cardiac hospitals often do CABG, TAVR, maybe abdominal aortic aneurysm (triple A) repairs, and they have cardiology clinics, cath labs, a cardiac intensive care unit (ICU), ER, etc. There were also orthopedic surgical specialty hospitals, which were sort of like an ambulatory surgery center (ASC) plus several beds. Then there were general surgical specialty hospitals. At one point, there were some women’s health–focused specialty hospitals.

The hospital industry, of course, as you can understand, didn’t exactly like this. They had a series of concerns about what we would historically call cherry-picking or lemon-dropping of patients. They were worried that physician-owned facilities didn’t want to serve public payer patients, and there was a whole series of reports and investigations.

Around the time the Affordable Care Act passed, the hospital industry had many concerns about physician-owned specialty hospitals, and there was a moratorium as part of the 2003 Medicare Modernization Act. As part of the bargaining over the hospital industry support for the Affordable Care Act, they traded their support for, among other things, their number one priority, which is a statutory prohibition on new or expanded physician-owned hospitals from participating in Medicare. That included both physician-owned community hospitals and physician-owned specialty hospitals.

Dr. Glatter: I guess the main interest is that, when physicians have an ownership or a stake in the hospital, this is what the Stark laws obviously were aimed at. That was part of the impetus to prevent physicians from referring patients where they had an ownership stake. Certainly, hospitals can be owned by attorneys and nonprofit organizations, and certainly, ASCs can be owned by physicians. There is an ongoing issue in terms of physicians not being able to have an ownership stake. In terms of equity ownership, we know that certain other models allow this, but basically, it sounds like this is an issue with Medicare. That seems to be the crux of it, correct?

Dr. Miller: Yes. I would also add that it’s interesting when we look at other professions. When we look at lawyers, nonlawyers are actually not allowed to own an equity stake in a law practice. In many other professions, you either have corporate ownership or professional ownership, or the alternative is you have only professional ownership. I would say the hospital industry is one of the few areas where professional ownership not only is not allowed, but also is statutorily prohibited functionally through the Medicare program.

Unveiling the Dynamics of Hospital Ownership

Dr. Glatter: A recent study done by two PhDs looked at 2019 data on 20 of the most expensive diagnosis-related groups (DRGs). It examined the cost savings, and we’re talking over $1 billion in expenditures when you look at the data from general acute care hospitals vs physician-owned hospitals. This is what appears to me to be a key driver of the push to loosen restrictions on physician-owned hospitals. Isn’t that correct?

Dr. Miller: I would say that’s one of many components. There’s more history to this issue. I remember sitting at a think tank talking to someone several years ago about hospital consolidation as an issue. We went through the usual levers that us policy wonks go through. We talked about antitrust enforcement, certificate of need, rising hospital costs from consolidation, lower quality (or at least no quality gains, as shown by a New England Journal of Medicine study), and decrements in patient experience that result from the diseconomies of scale. They sort of pooh-poohed many of the policy ideas. They basically said that there was no hope for hospital consolidation as an issue.

Well, what about physician ownership? I started with my research team to comb through the literature and found a variety of studies — some of which were sort of entertaining, because they’d do things like study physician-owned specialty hospitals, nonprofit-owned specialty hospitals, and for-profit specialty hospitals and compare them with nonprofit or for-profit community hospitals, and then say physician-owned hospitals that were specialty were bad.

They mixed ownership and service markets right there in so many ways, I’m not sure where to start. My team did a systematic review of around 30 years of research, looking at the evidence base in this space. We found a couple of things.

We found that physician-owned community hospitals did not have a cost or quality difference, meaning that there was no definitive evidence that the physician-owned community hospitals were cheaper based on historical evidence, which was very old. That means there’s not specific harm from them. When you permit market entry for community hospitals, that promotes competition, which results in lower prices and higher quality.

Then we also looked at the specialty hospital markets — surgical specialty hospitals, orthopedic surgical specialty hospitals, and cardiac hospitals. We noted for cardiac hospitals, there wasn’t clear evidence about cost savings, but there was definitive evidence of higher quality, from things like 30-day mortality for significant procedures like treatment of acute MI, triple A repair, stuff like that.

For orthopedic surgical specialty hospitals, we noted lower costs and higher quality, which again fits with operationally what we would know. If you have a facility that’s doing 20 total hips a day, you’re creating a focused factory. Just like if you think about it for interventional cardiology, your boards have a minimum number of procedures that you have to do to stay certified because we know about the volume-quality relationship.

Then we looked at general surgical specialty hospitals. There wasn’t enough evidence to make a conclusive thought about costs, and there was a clear trend toward higher quality. I would say this recent study is important, but there is a whole bunch of other literature out there, too.

Exploring the Scope of Emergency Care in Physician-Owned Hospitals

Dr. Glatter: Certainly, your colleague Wang from Johns Hopkins has done important research in this sector. The paper, “Reconsidering the Ban on Physician-Owned Hospitals to Combat Consolidation,” by you and several colleagues, mentions and highlights the issues that you just described. I understand that it’s going to be published in the NYU Journal of Legislation and Public Policy.

One thing I want to bring up — and this is an important issue — is that the risk for patients has been talked about by the American Hospital Association and the Federation of American Hospitals, in terms of limited or no emergency services at such physician-owned hospitals and having to call 911 when patients need emergent care or stabilization. That’s been the rebuttal, along with an Office of Inspector General (OIG) report from 2008. Almost, I guess, three quarters of the patients that needed emergent care got this at publicly funded hospitals.

Dr. Miller: I’m familiar with the argument about emergency care. If you actually go and look at it, it differs by specialty market. Physician-owned community hospitals have ERs because that’s how they get their business. If you are running a hospital medicine floor, a general surgical specialty floor, you have a labor delivery unit, a primary care clinic, and a cardiology clinic. You have all the things that all the other hospitals have. The physician-owned community hospitals almost uniformly have an ER.

When you look at the physician-owned specialty hospitals, it’s a little more granular. If you look at the cardiac hospitals, they have ERs. They also have cardiac ICUs, operating rooms, etc. The area where the hospital industry had concerns — which I think is valid to point out — is that physician-owned orthopedic surgical specialty hospitals don’t have ERs. But this makes sense because of what that hospital functionally is: a factory for whatever the scope of procedures is, be it joint replacements or shoulder arthroscopy. The orthopedic surgical specialty hospital is like an ASC plus several hospital beds. Many of those did not have ERs because clinically it didn’t make sense.

What’s interesting, though, is that the hospital industry also operates specialty hospitals. If you go into many of the large systems, they have cardiac specialty hospitals and cancer specialty hospitals. I would say that some of them have ERs, as they appropriately should, and some of those specialty hospitals do not. They might have a community hospital down the street that’s part of that health system that has an ER, but some of the specialty hospitals don’t necessarily have a dedicated ER.

I agree, that’s a valid concern. I would say, though, the question is, what are the scope of services in that hospital? Is an ER required? Community hospitals should have ERs. It makes sense also for a cardiac hospital to have one. If you’re running a total joint replacement factory, it might not make clinical sense.

Dr. Glatter: The patients who are treated at that hospital, if they do have emergent conditions, need to have board-certified emergency physicians treating them, in my view because I’m an ER physician. Having surgeons that are not emergency physicians staff a department at a specialty orthopedic hospital or, say, a cancer hospital is not acceptable from my standpoint. That›s my opinion and recommendation, coming from emergency medicine.

Dr. Miller: I would say that anesthesiologists are actually highly qualified in critical care. The question is about clinical decompensation; if you’re doing a procedure, you have an anesthesiologist right there who is capable of critical care. The function of the ER is to either serve as a window into the hospital for patient volume or to serve as a referral for emergent complaints.

Dr. Glatter: An anesthesiologist — I’ll take issue with that — does not have the training of an emergency physician in terms of scope of practice.

Dr. Miller: My anesthesiology colleagues would probably disagree for managing an emergency during an operating room case.

Dr. Glatter: Fair enough, but I think in the general sense. The other issue is that, in terms of emergent responses to patients that decompensate, when you have to transfer a patient, that violates Medicare requirements. How is that even a valid issue or argument if you’re going to have to transfer a patient from your specialty hospital? That happens. Again, I know that you’re saying these hospitals are completely independent and can function, stabilize patients, and treat emergencies, but that’s not the reality across the country, in my opinion.

Dr. Miller: I don’t think that’s the case for the physician-owned specialty cardiac hospitals, for starters. Many of those have ICUs in addition to operating rooms as a matter of routine in addition to ERs. I don’t think that’s the case for physician-owned community hospitals, which have ERs, ICUs, medicine floors, and surgical floors. Physician-owned community hospitals are around half the market. Of that remaining market, a significant percentage are cardiac hospitals. If you’re taking an issue with orthopedic surgical specialty hospitals, that’s a clinical operational question that can and should be answered.

I’d also posit that the nonprofit and for-profit hospital industries also operate specialty hospitals. Any of these questions, we shouldn’t just be asking about physician-owned facilities; we should be asking about them across ownership types, because we’re talking about scope of service and quality and safety. The ownership in that case doesn’t matter. The broader question is, are orthopedic surgical specialty hospitals owned by physicians, tax-exempt hospitals, or tax-paying hospitals? Is that a valid clinical business model? Is it safe? Does it meet Medicare conditions of participation? I would say that’s what that question is, because other ownership models do operate those facilities.

Dr. Glatter: You make some valid points, and I do agree on some of them. I think that, ultimately, these models of care, and certainly cost and quality, are issues. Again, it goes back to being able, in my opinion, to provide emergent care, which seems to me a very important issue.

Dr. Miller: I agree that providing emergent care is an issue. It›s an issue in any site of care. The hospital industry posits that all hospital outpatient departments (HOPDs) have emergent care. I can tell you, having worked in HOPDs (I›ve trained in them during residency), the response if something emergent happens is to either call 911 or wheel the patient down to the ER in a wheelchair or stretcher. I think that these hospital claims about emergency care coverage — these are important questions, but we should be asking them across all clinical settings and say what is the appropriate scope of care provided? What is the appropriate level of acuity and ability to provide emergent or critical care? That›s an important question regardless of ownership model across the entire industry.

Deeper Dive Into Data on Physician-Owned Hospitals

Dr. Glatter: We need to really focus on that. I’ll agree with you on that.

There was a March 2023 report from Dobson | DaVanzo. It showed that physician-owned hospitals had lower Medicaid, dual-eligible, and uncompensated care and charity care discharges than full-service acute care hospitals. Physician-owned hospitals had less than half the proportion of Medicaid discharges compared with non–physician-owned hospitals. They were also less likely to care for dual-eligible patients overall compared with non–physician-owned hospitals.

In addition, when COVID hit, the physician-owned hospitals overall — and again, there may be exceptions — were not equipped to handle these patient surges in the acute setting of a public health emergency. There was a hospital in Texas that did pivot that I’m aware of — Renaissance Hospital, which ramped up a long-term care facility to become a COVID hospital — but I think that’s the exception. I think this report raises some valid concerns; I’ll let you rebut that.

Dr. Miller: A couple of things. One, I am not aware that there’s any clear market evidence or a systematic study that shows that physician-owned hospitals had trouble responding to COVID. I don’t think that assertion has been proven. The study was funded by the hospital industry. First of all, it was not a peer-reviewed study; it was funded by an industry that paid a consulting firm. It doesn’t mean that we still shouldn’t read it, but that brings bias into question. The joke in Washington is, pick your favorite statistician or economist, and they can say what you want and have a battle of economists and statisticians.

For example, in that study, they didn’t include the entire ownership universe of physician-owned hospitals. If we go to the peer-reviewed literature, there’s a great 2015 BMJ paper showing that the Medicaid payer mix is actually the same between physician-owned hospitals vs not. The mix of patients by ethnicity — for example, think about African American patients — was the same. I would be more inclined to believe the peer-reviewed literature in BMJ as opposed to an industry-funded study that was not peer-reviewed and not independent and has methodological questions.

Dr. Glatter: Those data are 8 years old, so I’d like to see more recent data. It would be interesting, just as a follow-up to that, to see where the needle has moved — if it has, for that matter — in terms of Medicaid patients that you’re referring to.

Dr. Miller: I tend to be skeptical of all industry research, regardless of who published it, because they have an economic incentive. If they’re selecting certain age groups or excluding certain hospitals, that makes you wonder about the validity of the study. Your job as an industry-funded researcher is that, essentially, you’re being paid to look for an answer. It’s not necessarily an honest evaluation of the data.

Dr. Glatter: I want to bring up another point about the Hospital Readmissions Reduction Program (HRRP) and the data on how physician-owned hospitals compared with acute care hospitals that are non–physician-owned and have you comment on that. The Dobson | DaVanzo study called into question that physician-owned hospitals treat fewer patients who are dual-eligible, which we know.

Dr. Miller: I don’t think we do know that.

Dr. Glatter: There are data that point to that, again, looking at the studies.

Dr. Miller: I’m saying that’s a single study funded by industry as opposed to an independent, academic, peer-reviewed literature paper. That would be like saying, during the debate of the Inflation Reduction Act (IRA), that you should read the pharmaceutical industries research but take any of it at pure face value as factual. Yes, we should read it. Yes, we should evaluate it on its own merits. I think, again, appropriately, you need to be concerned when people have an economic incentive.

The question about the HRRP I’m going to take a little broader, because I think that program is unfair to the industry overall. There are many factors that drive hospital readmission. Whether Mrs Smith went home and ate potato chips and then took her Lasix, that’s very much outside of the hospital industry’s control, and there’s some evidence that the HRRP increases mortality in some patient populations.

In terms of a quality metric, it’s unfair to the industry. I think we took an operating process, internal metric for the hospital industry, turned it into a quality metric, and attached it to a financial bonus, which is an inappropriate policy decision.

Rethinking Ownership Models and Empowering Clinicians

Dr. Glatter: I agree with you on that. One thing I do want to bring up is that whether the physician-owned hospitals are subject to many of the quality measures that full-service, acute care hospitals are. That really is, I think, a broader context.

Dr. Miller: Fifty-five percent of physician-owned hospitals are full-service community hospitals, so I would say at least half the market is 100% subject to that.

Dr. Glatter: If only 50% are, that’s already an issue.

Dr. Miller: Cardiac specialty hospitals — which, as I said, nonprofit and for-profit hospital chains also operate — are also subject to the appropriate quality measures, readmissions, etc. Just because we don’t necessarily have the best quality measurement in the system in the country, it doesn’t mean that we shouldn’t allow care specialization. As I’d point out, if we’re concerned about specialty hospitals, the concern shouldn’t just be about physician-owned specialty hospitals; it should be about specialty hospitals by and large. Many health systems run cardiac specialty hospitals, cancer specialty hospitals, and orthopedic specialty hospitals. If we’re going to have a discussion about concerns there, it should be about the entire industry of specialty hospitals.

I think specialty hospitals serve an important role in society, allowing for specialization and exploiting in a positive way the volume-quality relationship. Whether those are owned by a for-profit publicly traded company, a tax-exempt facility, or physicians, I think that is an important way to have innovation and care delivery because frankly, we haven’t had much innovation in care delivery. Much of what we do in terms of how we practice clinically hasn’t really changed in the 50 years since my late father graduated from medical school. We still have rounds, we’re still taking notes, we’re still operating in the same way. Many processes are manual. We don’t have the mass production and mass customization of care that we need.

When you have a focused factory, it allows you to design care in a way that drives up quality, not just for the average patient but also the patients at the tail ends, because you have time to focus on that specific service line and that specific patient population.

Physician-owned community hospitals offer an important opportunity for a different employment model. I remember going to the dermatologist and the dermatologist was depressed, shuffling around the room, sad, and I asked him why. He said he didn’t really like his employer, and I said, “Why don’t you pick another one?” He’s like, “There are only two large health systems I can work for. They all have the same clinical practice environment and functionally the same value.”

Physicians are increasingly burned out. They face monopsony power in who purchases their labor. They have little control. They don’t want to go through five committees, seven administrators, and attend 25 meetings just to change a single small process in clinical operations. If you’re an owner operator, you have a much better ability to do it.

Frankly, when many facilities do well now, when they do well clinically and do well financially, who benefits? The hospital administration and the hospital executives. The doctors aren’t benefiting. The nurses aren’t benefiting. The CNA is not benefiting. The secretary is not benefiting. The custodian is not benefiting. Shouldn’t the workers have a right to own and operate the business and do well when the business does well serving the community? That puts me in the weird space of agreeing with both conservatives and progressives.

Dr. Glatter: I agree with you. I think an ownership stake is always attractive. It helps with retention of employed persons. There›s no question that, when they have a stake, when they have skin in the game, they feel more empowered. I will not argue with you about that.

Dr. Miller: We don’t have business models where workers have that option in healthcare. Like the National Academy of Medicine said, one of the key drivers of burnout is the externalization of the locus of control over clinical practice, and the current business operating models guarantee an externalization of the locus of control over clinical practice.

If you actually look at the recent American Medical Association (AMA) meeting, there was a resolution to ban the corporate practice of medicine. They wanted to go more toward the legal professions model where only physicians can own and operate care delivery.

Dr. Glatter: Well, I think the shift is certainly something that the AMA would like and physicians collectively would agree with. Having a better lifestyle and being able to have control are factors in burnout.

Dr. Miller: It’s not just doctors. I think nurses want a better lifestyle. The nurses are treated as interchangeable lines on a spreadsheet. The nurses are an integral part of our clinical team. Why don’t we work together as a clinical unit to build a better delivery system? What better way to do that than to have clinicians in charge of it, right?

My favorite bakery that’s about 30 minutes away is owned by a baker. It is not owned by a large tax-exempt corporation. It’s owned by an owner operator who takes pride in their work. I think that is something that the profession would do well to return to. When I was a resident, one of my colleagues was already planning their retirement. That’s how depressed they were.

I went into medicine to actually care for patients. I think that we can make the world a better place for our patients. What that means is not only treating them with drugs and devices, but also creating a delivery system where they don’t have to wander from lobby to lobby in a 200,000 square-foot facility, wait in line for hours on end, get bills 6 months later, and fill out endless paper forms over and over again.

All of these basic processes in healthcare delivery that are broken could have and should have been fixed — and have been fixed in almost every other industry. I had to replace one of my car tires because I had a flat tire. The local tire shop has an app, and it sends me SMS text messages telling me when my appointment is and when my car is ready. We have solved all of these problems in many other businesses.

We have not solved them in healthcare delivery because, one, we have massive monopolies that are raising prices, have lower quality, and deliver a crappy patient experience, and we have also subjugated the clinical worker into a corporate automaton. We are functionally drones. We don’t have the agency and the authority to improve clinical operations anymore. It’s really depressing, and we should have that option again.

I trust my doctor. I trust the nurses that I work with, and I would like them to help make clinical decisions in a financially responsible and a sensible operational manner. We need to empower our workforce in order to do that so we can recapture the value of what it means to be a clinician again.

The current model of corporate employment: massive scale, more administrators, more processes, more emails, more meetings, more PowerPoint decks, more federal subsidies. The hospital industry has choices. It can improve clinical operations. It can show up in Washington and lobby for increased subsidies. It can invest in the market and not pay taxes for the tax-exempt facilities. Obviously, it makes the logical choices as an economic actor to show up, lobby for increased subsidies, and then also invest in the stock market.

Improving clinical operations is hard. It hasn’t happened. The Bureau of Labor Statistics shows that the private community hospital industry has had flat labor productivity growth, on average, for the past 25 years, and for some years it even declined. This is totally atypical across the economy.

We have failed our clinicians, and most importantly, we have failed our patients. I’ve been sick. My relatives have been sick, waiting hours, not able to get appointments, and redoing forms. It’s a total disaster. It’s time and reasonable to try an alternative ownership and operating model. There are obviously problems. The problems can and should be addressed, but it doesn’t mean that we should have a statutory prohibition on professionals owning and operating their own business.

Dr. Glatter: There was a report that $500 million was saved by limiting or banning or putting a moratorium on physician-owned hospitals by the Congressional Budget Office.

Dr. Miller: Yes, I’m very aware of those data. I’d say that the CBO also is off by 50% on the estimation of the implementation of the Part D program. They overestimated the Affordable Care Act market enrollment by over 10 million people — again, around 50%. They also estimated that the CMS Innovation Center initially would be a savings. Now they’ve re-estimated it as a 10-year expenditure and it has actually cost the taxpayers money.

The CBO is not transparent about what its assumptions are or its analysis and methods. As a researcher, we have to publish our information. It has to go through peer review. I want to know what goes into that $500 million figure — what the assumptions are and what the model is. It’s hard to comment without knowing how they came up with it.

Dr. Glatter: The points you make are very valid. Physicians and nurses want a better lifestyle.

Dr. Miller: It’s not even a better lifestyle. It’s about having a say in how clinical operations work and helping make them better. We want the delivery system to work better. This is an opportunity for us to do so.

Dr. Glatter: That translates into technology: obviously, generative artificial intelligence (AI) coming into the forefront, as we know, and changing care delivery models as you’re referring to, which is going to happen. It’s going to be a slow process. I think that the evolution is happening and will happen, as you accurately described.

Dr. Miller: The other thing that’s different now vs 20 years ago is that managed care is here, there, and everywhere, as Dr Seuss would say. You have utilization review and prior authorization, which I’ve experienced as a patient and a physician, and boy, is it not a fun process. There’s a large amount of friction that needs to be improved. If we’re worried about induced demand or inappropriate utilization, we have managed care right there to help police bad behavior.

Reforming Healthcare Systems and Restoring Patient-Centric Focus

Dr. Glatter: If you were to come up with, say, three bullet points of how we can work our way out of this current morass of where our healthcare systems exist, where do you see the solutions or how can we make and effect change?

Dr. Miller: I’d say there are a couple of things. One is, let business models compete fairly on an equal playing field. Let the physician-owned hospital compete with the tax-exempt hospital and the nonprofit hospital. Put them on an equal playing field. We have things like 340B, which favors tax-exempt hospitals. For-profit or tax-paying hospitals are not able to participate in that. That doesn’t make any sense just from a public policy perspective. Tax-paying hospitals and physician-owned hospitals pay taxes on investments, but tax-exempt hospitals don’t. I think, in public policy, we need to equalize the playing field between business models. Let the best business model win.

The other thing we need to do is to encourage the adoption of technology. The physician will eventually be an arbiter of tech-driven or AI-driven tools. In fact, at some point, the standard of care might be to use those tools. Not using those tools would be seen as negligence. If you think about placing a jugular or central venous catheter, to not use ultrasound would be considered insane. Thirty years ago, to use ultrasound would be considered novel. I think technology and AI will get us to that point of helping make care more efficient and more customized.

Those are the two biggest interventions, I would say. Third, every time we have a conversation in public policy, we need to remember what it is to be a patient. The decision should be driven not around any one industry’s profitability, but what it is to be a patient and how we can make that experience less burdensome, less expensive, or in plain English, suck less.

Dr. Glatter: Safety net hospitals and critical access hospitals are part of this discussion that, yes, we want everything to, in an ideal world, function more efficiently and effectively, with less cost and less red tape. The safety net of our nation is struggling.

Dr. Miller: I 100% agree. The Cook County hospitals of the world are deserving of our support and, frankly, our gratitude. Facilities like that have huge burdens of patients with Medicaid. We also still have millions of uninsured patients. The neighborhoods that they serve are also poorer. I think facilities like that are deserving of public support.

I also think we need to clearly define what those hospitals are. One of the challenges I’ve realized as I waded into this space is that market definitions of what a service market is for a hospital, its specialty type or what a safety net hospital is need to be more clearly defined because those facilities 100% are deserving of our support. We just need to be clear about what they are.

Regarding critical access hospitals, when you practice in a rural area, you have to think differently about care delivery. I’d say many of the rural systems are highly creative in how they structure clinical operations. Before the public health emergency, during the COVID pandemic, when we had a massive change in telehealth, rural hospitals were using — within the very narrow confines — as much telehealth as they could and should.

Rural hospitals also make greater use of nurse practitioners (NPs) and physician assistants (PAs). For many of the specialty services, I remember, your first call was an NP or a PA because the physician was downstairs doing procedures. They’d come up and assess the patient before the procedure, but most of your consult questions were answered by the NP or PA. I’m not saying that’s the model we should use nationwide, but that rural systems are highly innovative and creative; they’re deserving of our time, attention, and support, and frankly, we can learn from them.

Dr. Glatter: I want to thank you for your time and your expertise in this area. We’ll see how the congressional hearings affect the industry as a whole, how the needle moves, and whether the ban or moratorium on physician-owned hospitals continues to exist going forward.

Dr. Miller: I appreciate you having me. The hospital industry is one of the most important industries for health care. This is a time of inflection, right? We need to go back to the value of what it means to be a clinician and serve patients. Hospitals need to reorient themselves around that core concern. How do we help support clinicians — doctors, nurses, pharmacists, whomever it is — in serving patients? Hospitals have become too corporate, so I think that this is an expected pushback.

Dr. Glatter: Again, I want to thank you for your time. This was a very important discussion. Thank you for your expertise.



Robert D. Glatter, MD, is an assistant professor of emergency medicine at Zucker School of Medicine at Hofstra/Northwell in Hempstead, New York. He is a medical advisor for Medscape and hosts the Hot Topics in EM series. He disclosed no relevant financial relationships.Brian J. Miller, MD, MBA, MPH, is a hospitalist and an assistant professor of medicine at the Johns Hopkins University School of Medicine. He is also a nonresident fellow at the American Enterprise Institute. From 2014 to 2017, Dr. Miller worked at four federal regulatory agencies: Federal Trade Commission (FTC), Federal Communications Commission (FCC), Centers for Medicare & Medicaid Services (CMS), and the Food & Drug Administration (FDA). Dr. Miller disclosed ties with the Medicare Payment Advisory Commission.
 

A version of this article appeared on Medscape.com.

A study published last spring suggesting that hearing aids may help reduce dementia risk has been retracted due to a coding error identified by the authors. 

The study was published April 13 in The Lancet Public Health and reported at that time. It was retracted by the journal on December 12.

According to the retraction notice, the journal editors in late November were informed by the authors of the paper that an error was introduced in the output format setting of their SAS codes, which led to data for people with hearing loss using hearing aids and those with hearing loss without using hearing aids being switched. 

This led to errors in their analysis, “which render their findings and conclusions false and misleading,” the retraction notice states. 

These errors were identified by the researchers following an exchange with scientists seeking to reproduce the authors’ findings.In a statement, The Lancet Group said it “takes issues relating to research integrity extremely seriously” and follows best-practice guidance from the Committee on Publication Ethics (COPE) and the International Committee of Medical Journal Editors (ICMJE). 

“Retractions are a rare but important part of the publishing process, and we are grateful to the scientists who prompted the re-examination of the data,” the statement reads. 

Despite the retraction, other studies have suggested a link between hearing and dementia. 

One study of US Medicare beneficiaries found a 61% higher dementia prevalence in those with moderate to severe hearing loss compared to those with normal hearing.

In this research, even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and use of hearing aids was tied to a 32% decrease in dementia prevalence. 

In addition, a large meta-analysis showed that hearing aids significantly reduce the risk for cognitive decline and dementia and even improve short-term cognitive function in individuals with hearing loss.

A version of this article appeared on Medscape.com.

A study published last spring suggesting that hearing aids may help reduce dementia risk has been retracted due to a coding error identified by the authors. 

The study was published April 13 in The Lancet Public Health and reported at that time. It was retracted by the journal on December 12.

According to the retraction notice, the journal editors in late November were informed by the authors of the paper that an error was introduced in the output format setting of their SAS codes, which led to data for people with hearing loss using hearing aids and those with hearing loss without using hearing aids being switched. 

This led to errors in their analysis, “which render their findings and conclusions false and misleading,” the retraction notice states. 

These errors were identified by the researchers following an exchange with scientists seeking to reproduce the authors’ findings.In a statement, The Lancet Group said it “takes issues relating to research integrity extremely seriously” and follows best-practice guidance from the Committee on Publication Ethics (COPE) and the International Committee of Medical Journal Editors (ICMJE). 

“Retractions are a rare but important part of the publishing process, and we are grateful to the scientists who prompted the re-examination of the data,” the statement reads. 

Despite the retraction, other studies have suggested a link between hearing and dementia. 

One study of US Medicare beneficiaries found a 61% higher dementia prevalence in those with moderate to severe hearing loss compared to those with normal hearing.

In this research, even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and use of hearing aids was tied to a 32% decrease in dementia prevalence. 

In addition, a large meta-analysis showed that hearing aids significantly reduce the risk for cognitive decline and dementia and even improve short-term cognitive function in individuals with hearing loss.

A version of this article appeared on Medscape.com.

A study published last spring suggesting that hearing aids may help reduce dementia risk has been retracted due to a coding error identified by the authors. 

The study was published April 13 in The Lancet Public Health and reported at that time. It was retracted by the journal on December 12.

According to the retraction notice, the journal editors in late November were informed by the authors of the paper that an error was introduced in the output format setting of their SAS codes, which led to data for people with hearing loss using hearing aids and those with hearing loss without using hearing aids being switched. 

This led to errors in their analysis, “which render their findings and conclusions false and misleading,” the retraction notice states. 

These errors were identified by the researchers following an exchange with scientists seeking to reproduce the authors’ findings.In a statement, The Lancet Group said it “takes issues relating to research integrity extremely seriously” and follows best-practice guidance from the Committee on Publication Ethics (COPE) and the International Committee of Medical Journal Editors (ICMJE). 

“Retractions are a rare but important part of the publishing process, and we are grateful to the scientists who prompted the re-examination of the data,” the statement reads. 

Despite the retraction, other studies have suggested a link between hearing and dementia. 

One study of US Medicare beneficiaries found a 61% higher dementia prevalence in those with moderate to severe hearing loss compared to those with normal hearing.

In this research, even mild hearing loss was associated with increased dementia risk, although it was not statistically significant, and use of hearing aids was tied to a 32% decrease in dementia prevalence. 

In addition, a large meta-analysis showed that hearing aids significantly reduce the risk for cognitive decline and dementia and even improve short-term cognitive function in individuals with hearing loss.

A version of this article appeared on Medscape.com.

Human microbiome research has progressed in leaps and bounds over the past decades, from pivotal studies begun in the 1970s to the launch of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for more recent clinical applications, such as fecal microbiota transplantation (FMT), and advanced techniques to explore new therapeutic pathways. Yet the “microbiome revolution” is just getting started, according to professor Martin J. Blaser, MD, one of the field’s pioneers.

The ongoing research and clinical trials into the microbiome’s link to the major causes of death in the United States hold the promise of interventions that manipulate the microbiome to prevent, slow, or perhaps even cure these conditions, says Dr. Blaser, who holds the Henry Rutgers Chair of the Human Microbiome and is director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey.

Dr. Blaser is the author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, serves as chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria and is a member of the scientific advisory board of the biotech startup Micronoma.

In this interview, which has been condensed and edited for clarity, Dr. Blaser discusses where we’re at now and where he sees the microbiome field evolving in the coming years.

Highlighting the Most Promising Applications

Which recent studies on the link between the human microbiome and disease have you found particularly promising?

There have been a number of studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces, or detoxifies, metabolites that are toxic to the kidney: for example, those involved in the formation of kidney stones and in the worsening of uremia. 

Altering the microbiome to reduce the uremic toxins and the nidus for stone formation is a very promising field of research. 

What other disease states may be amenable to microbiome-based interventions?

There are diseases that are caused by known genetic mutations. Yet, for nearly all of them, there is great variation in clinical outcomes, which might be classed as genes multiplied by environment interactions. 

It seems likely to me that microbiome variation could account for some proportion of those differences for some genetic diseases. 

It’s now well established that altering the microbiome with FMT is a successful intervention for recurrent  Clostridioides difficile  infections. What do you see as the next disease states where FMT could prove successful?

If you go to ClinicalTrials.gov, you will find that that there are 471 trials registered using FMT. This is across a broad range of illnesses, including metabolic, immunological, autoimmune, inflammatory, degenerative, and neoplastic diseases. 

Which will be the next condition showing marked efficacy is anyone’s guess. That is why we must do clinical trials to assess what works and what does not, regardless of specific illness. 

The donor’s microbiome appears to be vital to engraftment success, with “superdonors” even being identified. What factors do you think primarily influence microbiome engraftment?

There is an emerging science about this question, driven in part by classical ecological theory. 

Right now, we are using FMT as if one size fits all. But this probably would not provide optimal treatment for all. Just as we type blood donors and recipients before the blood transfusion, one could easily imagine a parallel kind of procedure. 

Are there any diseases where it’s just too far-fetched to think altering the microbiome could make a difference?

The link between the microbiome and human health is so pervasive that there are few conditions that are out of the realm of possibility. It really is a frontier. 

Not that the microbiome causes everything, but by understanding and manipulating the microbiome, we could at least palliate, or slow down, particular pathologic processes. 

For all the major causes of death in the United States — cardiovascular disease, cancer, dementia and neurogenerative diseases, diabetes, and lung, liver, and kidney diseases — there is ongoing investigation of the microbiome. A greater promise would be to prevent or cure these illnesses. 

Predicting the Next Stages of the ‘Microbiome Revolution’

Do you believe we are at a turning point with the microbiome in terms of being able to manipulate or engineer it?

The microbiome is a scientific frontier that has an impact across the biosphere. It is a broad frontier involving human and veterinary medicine, agriculture, and the environment. Knowledge is increasing incrementally, as expected. 

Are we at the point yet where doctors should be incorporating microbiome-related lifestyle changes for people with or at risk for cancer, heart disease, Alzheimer’s disease, or other chronic conditions?

Although we are still in the early stages of the “microbiome revolution,” which I first wrote about in EMBO Reports  in 2006 and then again in the Journal of Clinical Investigation in 2014, I think important advances for all of these conditions are coming our way in the next 5-10 years. 

How are prebiotics, probiotics, and postbiotics being used to shape the microbiome?

This is a very important and active area in clinical investigation, which needs to be ramped up. 

Tens of millions of people are using probiotics and prebiotics every day for vague indications, and which have only infrequently been tested in robust clinical trials. So, there is a disconnect between what’s being claimed with the bulk of the probiotics at present and what we’ll actually know in the future. 

How do you think the microbiome will stack up to other factors influencing health, such as genetics, exercise, and nutrition?

All are important, but unlike genetics, the microbiome is tractable, like diet and exercise. 

It is essentially impossible to change one’s genome, but that might become more likely before too long. However, we can easily change someone’s microbiome through dietary means, for example. Once we know the ground rules, there will be many options. Right now, it is mostly one-offs, but as the scientific basis broadens, much more will be possible. 

In the future, do you think we’ll be able to look at a person’s microbiome and tell what his or her risk of developing disease is, similar to the way we use gene panels now?

Yes, but we will need scientific advances to teach us what are the important biomarkers in general and in particular people. This will be one area of precision medicine. 

Lessons From Decades at the Forefront

You’ve been involved in this research for over 30 years, and the majority has focused on the human microbiome and its role in disease. When did it become apparent to you that this research had unique therapeutic promise?

From the very start, there was always the potential to harness the microbiome to improve human health. In fact, I wrote a perspective in PNAS on that theme in 2010. 

The key is to understand the biology of the microbiome, and from the scientific study comes new preventives and new treatments. Right now, there are many “probiotic” products on the market. Probiotics have a great future, but most of what is out there has not been rigorously tested for effectiveness. 

Was there a particular series of studies that occurred before the launch of the Human Microbiome Project and brought us to the current era?

The studies in the 1970s-1980s by Carl Woese using 16S rRNA genes to understand phylogeny and evolution opened up the field of DNA sequencing to consider bacterial evolution and issues of ancestry. 

A key subject of your research and the focus of your book is antibiotic-resistant bacteria. What did this work teach you about describing the science of antibiotic resistance to the general public?

People don’t care very much about antibiotic resistance. They think that affects other people, mostly. In contrast, they care about their own health and their children’s health. 

The more that the data show that using antibiotics can be harmful to health in some circumstances, the more that use will diminish. We need more transparency about benefits and costs. 

Are there any common misconceptions about the microbiome that you hear from the general public, or even clinicians, that you would like to see greater efforts to dispel?

The public and the medical profession are in love with probiotics, buying them by the tens of millions. But as stated before, they are very diverse and mostly untested for efficacy. 

The next step is to test specific formulations to see which ones work, and for whom, and which ones don’t. That would be a big advance. 

A version of this article appeared on Medscape.com.

Human microbiome research has progressed in leaps and bounds over the past decades, from pivotal studies begun in the 1970s to the launch of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for more recent clinical applications, such as fecal microbiota transplantation (FMT), and advanced techniques to explore new therapeutic pathways. Yet the “microbiome revolution” is just getting started, according to professor Martin J. Blaser, MD, one of the field’s pioneers.

The ongoing research and clinical trials into the microbiome’s link to the major causes of death in the United States hold the promise of interventions that manipulate the microbiome to prevent, slow, or perhaps even cure these conditions, says Dr. Blaser, who holds the Henry Rutgers Chair of the Human Microbiome and is director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey.

Dr. Blaser is the author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, serves as chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria and is a member of the scientific advisory board of the biotech startup Micronoma.

In this interview, which has been condensed and edited for clarity, Dr. Blaser discusses where we’re at now and where he sees the microbiome field evolving in the coming years.

Highlighting the Most Promising Applications

Which recent studies on the link between the human microbiome and disease have you found particularly promising?

There have been a number of studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces, or detoxifies, metabolites that are toxic to the kidney: for example, those involved in the formation of kidney stones and in the worsening of uremia. 

Altering the microbiome to reduce the uremic toxins and the nidus for stone formation is a very promising field of research. 

What other disease states may be amenable to microbiome-based interventions?

There are diseases that are caused by known genetic mutations. Yet, for nearly all of them, there is great variation in clinical outcomes, which might be classed as genes multiplied by environment interactions. 

It seems likely to me that microbiome variation could account for some proportion of those differences for some genetic diseases. 

It’s now well established that altering the microbiome with FMT is a successful intervention for recurrent  Clostridioides difficile  infections. What do you see as the next disease states where FMT could prove successful?

If you go to ClinicalTrials.gov, you will find that that there are 471 trials registered using FMT. This is across a broad range of illnesses, including metabolic, immunological, autoimmune, inflammatory, degenerative, and neoplastic diseases. 

Which will be the next condition showing marked efficacy is anyone’s guess. That is why we must do clinical trials to assess what works and what does not, regardless of specific illness. 

The donor’s microbiome appears to be vital to engraftment success, with “superdonors” even being identified. What factors do you think primarily influence microbiome engraftment?

There is an emerging science about this question, driven in part by classical ecological theory. 

Right now, we are using FMT as if one size fits all. But this probably would not provide optimal treatment for all. Just as we type blood donors and recipients before the blood transfusion, one could easily imagine a parallel kind of procedure. 

Are there any diseases where it’s just too far-fetched to think altering the microbiome could make a difference?

The link between the microbiome and human health is so pervasive that there are few conditions that are out of the realm of possibility. It really is a frontier. 

Not that the microbiome causes everything, but by understanding and manipulating the microbiome, we could at least palliate, or slow down, particular pathologic processes. 

For all the major causes of death in the United States — cardiovascular disease, cancer, dementia and neurogenerative diseases, diabetes, and lung, liver, and kidney diseases — there is ongoing investigation of the microbiome. A greater promise would be to prevent or cure these illnesses. 

Predicting the Next Stages of the ‘Microbiome Revolution’

Do you believe we are at a turning point with the microbiome in terms of being able to manipulate or engineer it?

The microbiome is a scientific frontier that has an impact across the biosphere. It is a broad frontier involving human and veterinary medicine, agriculture, and the environment. Knowledge is increasing incrementally, as expected. 

Are we at the point yet where doctors should be incorporating microbiome-related lifestyle changes for people with or at risk for cancer, heart disease, Alzheimer’s disease, or other chronic conditions?

Although we are still in the early stages of the “microbiome revolution,” which I first wrote about in EMBO Reports  in 2006 and then again in the Journal of Clinical Investigation in 2014, I think important advances for all of these conditions are coming our way in the next 5-10 years. 

How are prebiotics, probiotics, and postbiotics being used to shape the microbiome?

This is a very important and active area in clinical investigation, which needs to be ramped up. 

Tens of millions of people are using probiotics and prebiotics every day for vague indications, and which have only infrequently been tested in robust clinical trials. So, there is a disconnect between what’s being claimed with the bulk of the probiotics at present and what we’ll actually know in the future. 

How do you think the microbiome will stack up to other factors influencing health, such as genetics, exercise, and nutrition?

All are important, but unlike genetics, the microbiome is tractable, like diet and exercise. 

It is essentially impossible to change one’s genome, but that might become more likely before too long. However, we can easily change someone’s microbiome through dietary means, for example. Once we know the ground rules, there will be many options. Right now, it is mostly one-offs, but as the scientific basis broadens, much more will be possible. 

In the future, do you think we’ll be able to look at a person’s microbiome and tell what his or her risk of developing disease is, similar to the way we use gene panels now?

Yes, but we will need scientific advances to teach us what are the important biomarkers in general and in particular people. This will be one area of precision medicine. 

Lessons From Decades at the Forefront

You’ve been involved in this research for over 30 years, and the majority has focused on the human microbiome and its role in disease. When did it become apparent to you that this research had unique therapeutic promise?

From the very start, there was always the potential to harness the microbiome to improve human health. In fact, I wrote a perspective in PNAS on that theme in 2010. 

The key is to understand the biology of the microbiome, and from the scientific study comes new preventives and new treatments. Right now, there are many “probiotic” products on the market. Probiotics have a great future, but most of what is out there has not been rigorously tested for effectiveness. 

Was there a particular series of studies that occurred before the launch of the Human Microbiome Project and brought us to the current era?

The studies in the 1970s-1980s by Carl Woese using 16S rRNA genes to understand phylogeny and evolution opened up the field of DNA sequencing to consider bacterial evolution and issues of ancestry. 

A key subject of your research and the focus of your book is antibiotic-resistant bacteria. What did this work teach you about describing the science of antibiotic resistance to the general public?

People don’t care very much about antibiotic resistance. They think that affects other people, mostly. In contrast, they care about their own health and their children’s health. 

The more that the data show that using antibiotics can be harmful to health in some circumstances, the more that use will diminish. We need more transparency about benefits and costs. 

Are there any common misconceptions about the microbiome that you hear from the general public, or even clinicians, that you would like to see greater efforts to dispel?

The public and the medical profession are in love with probiotics, buying them by the tens of millions. But as stated before, they are very diverse and mostly untested for efficacy. 

The next step is to test specific formulations to see which ones work, and for whom, and which ones don’t. That would be a big advance. 

A version of this article appeared on Medscape.com.

Human microbiome research has progressed in leaps and bounds over the past decades, from pivotal studies begun in the 1970s to the launch of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for more recent clinical applications, such as fecal microbiota transplantation (FMT), and advanced techniques to explore new therapeutic pathways. Yet the “microbiome revolution” is just getting started, according to professor Martin J. Blaser, MD, one of the field’s pioneers.

The ongoing research and clinical trials into the microbiome’s link to the major causes of death in the United States hold the promise of interventions that manipulate the microbiome to prevent, slow, or perhaps even cure these conditions, says Dr. Blaser, who holds the Henry Rutgers Chair of the Human Microbiome and is director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey.

Dr. Blaser is the author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, serves as chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria and is a member of the scientific advisory board of the biotech startup Micronoma.

In this interview, which has been condensed and edited for clarity, Dr. Blaser discusses where we’re at now and where he sees the microbiome field evolving in the coming years.

Highlighting the Most Promising Applications

Which recent studies on the link between the human microbiome and disease have you found particularly promising?

There have been a number of studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces, or detoxifies, metabolites that are toxic to the kidney: for example, those involved in the formation of kidney stones and in the worsening of uremia. 

Altering the microbiome to reduce the uremic toxins and the nidus for stone formation is a very promising field of research. 

What other disease states may be amenable to microbiome-based interventions?

There are diseases that are caused by known genetic mutations. Yet, for nearly all of them, there is great variation in clinical outcomes, which might be classed as genes multiplied by environment interactions. 

It seems likely to me that microbiome variation could account for some proportion of those differences for some genetic diseases. 

It’s now well established that altering the microbiome with FMT is a successful intervention for recurrent  Clostridioides difficile  infections. What do you see as the next disease states where FMT could prove successful?

If you go to ClinicalTrials.gov, you will find that that there are 471 trials registered using FMT. This is across a broad range of illnesses, including metabolic, immunological, autoimmune, inflammatory, degenerative, and neoplastic diseases. 

Which will be the next condition showing marked efficacy is anyone’s guess. That is why we must do clinical trials to assess what works and what does not, regardless of specific illness. 

The donor’s microbiome appears to be vital to engraftment success, with “superdonors” even being identified. What factors do you think primarily influence microbiome engraftment?

There is an emerging science about this question, driven in part by classical ecological theory. 

Right now, we are using FMT as if one size fits all. But this probably would not provide optimal treatment for all. Just as we type blood donors and recipients before the blood transfusion, one could easily imagine a parallel kind of procedure. 

Are there any diseases where it’s just too far-fetched to think altering the microbiome could make a difference?

The link between the microbiome and human health is so pervasive that there are few conditions that are out of the realm of possibility. It really is a frontier. 

Not that the microbiome causes everything, but by understanding and manipulating the microbiome, we could at least palliate, or slow down, particular pathologic processes. 

For all the major causes of death in the United States — cardiovascular disease, cancer, dementia and neurogenerative diseases, diabetes, and lung, liver, and kidney diseases — there is ongoing investigation of the microbiome. A greater promise would be to prevent or cure these illnesses. 

Predicting the Next Stages of the ‘Microbiome Revolution’

Do you believe we are at a turning point with the microbiome in terms of being able to manipulate or engineer it?

The microbiome is a scientific frontier that has an impact across the biosphere. It is a broad frontier involving human and veterinary medicine, agriculture, and the environment. Knowledge is increasing incrementally, as expected. 

Are we at the point yet where doctors should be incorporating microbiome-related lifestyle changes for people with or at risk for cancer, heart disease, Alzheimer’s disease, or other chronic conditions?

Although we are still in the early stages of the “microbiome revolution,” which I first wrote about in EMBO Reports  in 2006 and then again in the Journal of Clinical Investigation in 2014, I think important advances for all of these conditions are coming our way in the next 5-10 years. 

How are prebiotics, probiotics, and postbiotics being used to shape the microbiome?

This is a very important and active area in clinical investigation, which needs to be ramped up. 

Tens of millions of people are using probiotics and prebiotics every day for vague indications, and which have only infrequently been tested in robust clinical trials. So, there is a disconnect between what’s being claimed with the bulk of the probiotics at present and what we’ll actually know in the future. 

How do you think the microbiome will stack up to other factors influencing health, such as genetics, exercise, and nutrition?

All are important, but unlike genetics, the microbiome is tractable, like diet and exercise. 

It is essentially impossible to change one’s genome, but that might become more likely before too long. However, we can easily change someone’s microbiome through dietary means, for example. Once we know the ground rules, there will be many options. Right now, it is mostly one-offs, but as the scientific basis broadens, much more will be possible. 

In the future, do you think we’ll be able to look at a person’s microbiome and tell what his or her risk of developing disease is, similar to the way we use gene panels now?

Yes, but we will need scientific advances to teach us what are the important biomarkers in general and in particular people. This will be one area of precision medicine. 

Lessons From Decades at the Forefront

You’ve been involved in this research for over 30 years, and the majority has focused on the human microbiome and its role in disease. When did it become apparent to you that this research had unique therapeutic promise?

From the very start, there was always the potential to harness the microbiome to improve human health. In fact, I wrote a perspective in PNAS on that theme in 2010. 

The key is to understand the biology of the microbiome, and from the scientific study comes new preventives and new treatments. Right now, there are many “probiotic” products on the market. Probiotics have a great future, but most of what is out there has not been rigorously tested for effectiveness. 

Was there a particular series of studies that occurred before the launch of the Human Microbiome Project and brought us to the current era?

The studies in the 1970s-1980s by Carl Woese using 16S rRNA genes to understand phylogeny and evolution opened up the field of DNA sequencing to consider bacterial evolution and issues of ancestry. 

A key subject of your research and the focus of your book is antibiotic-resistant bacteria. What did this work teach you about describing the science of antibiotic resistance to the general public?

People don’t care very much about antibiotic resistance. They think that affects other people, mostly. In contrast, they care about their own health and their children’s health. 

The more that the data show that using antibiotics can be harmful to health in some circumstances, the more that use will diminish. We need more transparency about benefits and costs. 

Are there any common misconceptions about the microbiome that you hear from the general public, or even clinicians, that you would like to see greater efforts to dispel?

The public and the medical profession are in love with probiotics, buying them by the tens of millions. But as stated before, they are very diverse and mostly untested for efficacy. 

The next step is to test specific formulations to see which ones work, and for whom, and which ones don’t. That would be a big advance. 

A version of this article appeared on Medscape.com.