MDedge Infectious Disease

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

courtesy Tulane University-Paula Burch-Celentano

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

courtesy Tulane University-Paula Burch-Celentano

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

Several recent developments in Lyme disease treatment and diagnosis may pave the way forward for combating disease that persists following missed or delayed diagnoses or remains following standard treatment. These include combination therapy to address “persister” bacteria and diagnostic tests that test directly for the pathogen and/or indirectly test for host response, according to experts who presented at a 2-day National Academies of Science, Engineering and Medicine workshop on infection-associated chronic illnesses.

Research has shown that 60% of people who are infected and not treated during the early or early disseminated stages of Lyme disease go on to develop late Lyme arthritis, said John Aucott, MD, director of the Johns Hopkins Lyme Disease Clinical Research Center in Baltimore. And in the real world, there’s an additional category of patients: Those who are misdiagnosed and develop infection-related persistent symptoms – such as fatigue, brain fog/cognitive dysfunction, and musculoskeletal problems – that don’t match the “textbook schematic” involving late Lyme arthritis and late neurologic disease.

Moreover, of patients who are treated with protocols recommended by the Infectious Diseases Society of America (IDSA), about 15% go on to develop persistent symptoms at 6 months – again, symptoms that don’t match textbook manifestations and do match symptoms of other infection-associated chronic illnesses. As a “research construct,” this has been coined posttreatment Lyme disease (PTLD), he said at the workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

(On a practical level, it is hard to know clinically who has early disseminated disease unless they have multiple erythema migrans rashes or neurologic or cardiac involvement, he said after the meeting.)

All this points to the need for tests that are sensitive and specific for diagnosis at all stages of infection and disease, he said in a talk on diagnostics. Currently available tests – those that fit into the widely used two-tiered enzyme-linked immunosorbent assay, Western Blot serology testing – have significant limitations in sensitivity and specificity, including for acute infection when the body has not generated enough antibodies, yet treatment is most likely to succeed.
 

Move toward combination therapy research

Lyme disease is most commonly treated with doxycycline, and that’s problematic because the antibiotic is a microstatic whose efficacy relies on immune clearance of static bacteria, said Monica E. Embers, PhD, director of vector-borne disease at the Tulane National Primate Research Center and associate professor of immunology at Tulane University, New Orleans.

courtesy Tulane University-Paula Burch-Celentano

“But we know that Borrelia burgdorferi has the capability to evade the host immune response in almost every way possible. Persistence is the norm in an immunocompetent host ... [and] dormant bacteria/persisters are more tolerant of microstatic antibiotics,” she said.

Other considerations for antibiotic efficacy include the fact that B. burgdorferi survives for many months inside ticks without nutrient replenishment or replication, “so dormancy is part of their life cycle,” she said. Moreover, the bacteria can be found deep in connective tissues and joints.

The efficacy of accepted regimens of antibiotic treatment has been “a very contentious issue,” she said, noting that guidelines from the International Lyme and Associated Diseases Society “leave open the possibility for antibiotic retreatment when a chronic infection is judged to be a possible cause [of ongoing symptoms].”

The development of persister B. burgdorferi in the presence of antibiotics has been well studied in vitro, which has limitations, Dr. Embers said. But her group specializes in animal models and has shown persistence of antimicrobial-tolerant B. burgdorferi in tick-inoculated rhesus macaques 8-9 months after treatment with oral doxycycline.

“We [also] saw persistence of mild-moderate inflammation in the brain, peripheral nerves, spinal cord, joints and skeletal muscle, and in the heart,” Dr. Embers said, who coauthored a 2022 review of B. burgdorferi antimicrobial-tolerant persistence in Lyme disease and PTLD.

Her work has also shown that ceftriaxone, which is recommended by IDSA for patients with clinically evident neurological and/or cardiac involvement, does not clear infection in mice. “In general, single drugs have not been capable of clearing the infection, yet combinations show promise,” she said.

Dr. Embers has combed large drug libraries looking for combinations of antibiotics that employ different mechanisms of action in hopes of eliminating persister spirochetes. Certain combinations have shown promise in mice and have been tested in her rhesus macaque model; data analyses are underway.

Other research teams, such as that of Ying Zhang, MD, PhD, at Johns Hopkins, have similarly been screening combinations of antibiotics and other compounds, identifying candidates for further testing.

During a question and answer period, Dr. Embers said her team is also investigating the pathophysiology and long-term effects of tick-borne coinfections, including Bartonella, and is pursuing a hypothesis that infection with Borrelia allows Bartonella to cause more extensive disease and persist longer. “I think Lyme is at the core because of its ability to evade and suppress the immune response so effectively.”
 

Diagnostic possibilities, biomarkers for PTLD

Direct diagnostic tests for microbial nucleic acid and proteins “are promising alternatives for indirect serologic tests,” Dr. Aucott said. For instance, in addition to polymerase chain reaction tests, which “are making advances,” it may be possible to target the B. burgdorferi peptidoglycan for antigen detection.

Researchers have shown that peptidoglycan, a component of the B. burgdorferi cell envelope, is a persistent antigen in the synovial fluid of patients with Lyme arthritis who have been treated with oral and intravenous antibiotics, and that it likely contributes to inflammation.

“Maybe the infection is gone but parts of the bacteria are still there that are driving inflammation,” said Dr. Aucott, also associate professor of medicine at John Hopkins.

Researchers have also been looking at the host response to B. burgdorferi – including cytokines, chemokines, and autoantibiodies – to identify biomarkers for PTLD and to identify patients during posttreatment follow-up who are at increased risk of developing PTLD, with the hope of someday intervening. Persistently high levels of interleukin-23, CCL19, and interferon-alpha have each been associated in different studies with persistent symptoms after treatment, Dr. Aucott said.

In addition, metabolomics research is showing that patients with PTLD have metabolic fingerprints that are different from those who return to good health after treatment, and it may be possible to identify an epigenetic signature for Lyme disease. A project sponsored by the Defense Advanced Research Projects Agency called ECHO (Epigenetic Characterization and Observation) aims to identify epigenetic signatures of exposures to various threats, including B. burgdorferi.

“At the very proximal end of [indirectly testing for host response], there are modifications of the DNA that can occur in response to infectious insults ... and that changed DNA changes RNA expression and protein synthesis,” Dr. Aucott explained. DARPA’s project is “exciting because their goal [at DARPA] is to have a diagnostic test quickly as a result of this epigenetics work.”

Imaging research is also fast offering diagnostic opportunities, Dr. Aucott said. Levels of microglial activation on brain PET imaging have been found to correlate with PTLD, and a study at Johns Hopkins of multimodal neuroimaging with functional MRI and diffusion tensor imaging has shown distinct changes to white matter activation within the frontal lobe of patients with PTLD, compared with controls.

The NASEM workshop did not collect or require disclosures of its participants.

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

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

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

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

Like hundreds of other medical experts, Leana Wen, MD, an emergency physician and former Baltimore health commissioner, was an early and avid supporter of COVID vaccines and their ability to prevent severe disease, hospitalization, and death from SARS-CoV-2 infections.

When 51-year-old Scott Eli Harris, of Aubrey, Tex., heard of Dr. Wen’s stance in July 2021, the self-described “fifth-generation U.S. Army veteran and a sniper” sent Dr. Wen an electronic invective laden with racist language and very specific threats to shoot her.

Mr. Harris pled guilty to transmitting threats via interstate commerce last February and began serving 6 months in federal prison in the fall of 2022, but his threats wouldn’t be the last for Dr. Wen. Just 2 days after Mr. Harris was sentenced, charges were unsealed against another man in Massachusetts, who threatened that Dr. Wen would “end up in pieces” if she continued “pushing” her thoughts publicly.’

Dr. Wen has plenty of company. In an August 2022 survey of emergency doctors conducted by the American College of Emergency Physicians, 85% of respondents said violence against them is increasing. One in four doctors said they’re being assaulted by patients and their family and friends multiple times a week, compared with just 8% of doctors who said as much in 2018. About 64% of emergency physicians reported receiving verbal assaults and threats of violence; 40% reported being hit or slapped, and 26% were kicked.

This uptick of violence and threats against physicians didn’t come out of nowhere; violence against health care workers has been gradually increasing over the past decade. Health care providers can attest to the hostility that particular topics have sparked for years: vaccines in pediatrics, abortion in ob.gyn., and gender-affirming care in endocrinology.

But the pandemic fueled the fire. While there have always been hot-button issues in medicine, the ire they arouse today is more intense than ever before. The proliferation of misinformation (often via social media) and the politicization of public health and medicine are at the center of the problem.
 

‘The people attacking are themselves victims’

The misinformation problem first came to a head in one area of public health: vaccines. The pandemic accelerated antagonism in medicine – thanks, in part, to decades of antivaccine activism.

The antivaccine movement, which has ebbed and flowed in the United States and across the globe since the first vaccine, experienced a new wave in the early 2000s with the combination of concerns about thimerosal in vaccines and a now disproven link between autism and the MMR vaccine. But that movement grew. It picked up steam when activists gained political clout after a 2014 measles outbreak at Disneyland led California schools to tighten up policies regarding vaccinations for kids who enrolled. These stronger public school vaccination laws ran up against religious freedom arguments from antivaccine advocates.

Use of social media continues to grow, and with it, the spread of misinformation. A recent study found that Facebook “users’ social media habits doubled, and in some cases, tripled the amount of fake news they shared.”

In the face of growing confusion, health care providers and public health experts have often struggled to treat their patients – and communicate to the public – without appearing political.

“The people that are doing the attacking are in some ways themselves victims,” said Peter Hotez, MD, PhD, dean of the National School of Tropical Medicine at Baylor College of Medicine, Houston. “They’re victims of the antiscience, antihealth ecosystem coming out of Fox News, the House Freedom Caucus, the CPAC conference, coming out of contrarian intellectuals.”

Many of Dr. Hotez’s colleagues don’t want to talk about the political right as an enabler of scientific disinformation, he said, but that doesn’t change what the evidence shows. The vast majority of state and national bills opposing vaccination, gender-affirming care, comprehensive reproductive care, and other evidence-based medical care often come from Republican legislators.
 

When politics and health care collide

“We’re in an incredible status quo,” said William Schaffner, MD, the previous director of the Infectious Diseases Society of America and a professor of infectious diseases and preventive medicine at Vanderbilt University, Nashville, Tenn. “You can’t get away from the politics, because you have [political] candidates espousing certain concepts that are antithetical to good public health.”

In March 2023, Florida Gov. Ron DeSantis’s surgeon general, Joseph Ladapo, MD, PhD, warned that COVID vaccines are harmful to young men, prompting rebukes from federal health authorities. It later came out that Dr. Ladapo had changed some of the results of the study before issuing his warning. But long before 2023, there emerged an increasing gap in COVID deaths between red states and blue states, mirroring the vaccination rates in those states. The redder the state, the higher the death toll.

It’s not just Republican Party culture warriors; medical misinformation is also finding increasing purchase on the far left. Robert F. Kennedy Jr. and Marianne Williamson, both of whom have launched long-shot challenges to President Biden for the 2024 Democratic nomination, had promoted antivaccine ideas long before the COVID pandemic. Mr. Kennedy continues to spread misinformation.

In June 2023, Joe Rogan hosted Mr. Kennedy, on his podcast. During the episode, Mr. Rogan listened uncritically as Mr. Kennedy told his millions of listeners that vaccines cause autism and that 5G causes cancer, among other fringe, often-debunked theories.

Dr. Hotez, a prominent misinformation debunker who was also part of a team that designed a low-cost COVID-19 vaccine, wrote on Twitter that the episode was “just awful.”

The backlash began almost immediately. Mr. Rogan, who has over 11 million followers on Twitter, responded with a public challenge for Dr. Hotez to debate Mr. Kennedy on Mr. Rogan’s show, with a reward of $100,000 to the charity of Dr. Hotez’s choice. More offers streamed in, including from Elon Musk, who tweeted that Dr. Hotez was “afraid of a public debate, because he knows he’s wrong.” More supporters of Mr. Kennedy and Mr. Rogan piled on.

Vaccine skeptics even showed up at Dr. Hotez’s house, filming him as he was returning from buying a Father’s Day cake and taunting him to debate Mr. Kennedy.
 

A turn in the pandemic

For a precious few weeks at the start of the pandemic, it felt as though the country was all in this together. There were arguments against closing schools and shutting down businesses, but for the most part, the nation had about 4 solid weeks of solidarity.

As masking mandates changed and the public health establishment lost the confidence of Americans, the veneer of solidarity began to chip away.

“Things were changing so rapidly during the pandemic that it was very hard for staff and patients to understand the changing guidelines, whether it was visitor constraints or masking,” said Carrie Nelson, the chief medical officer at the telehealth company AmWell, who worked as a supervisor at a large health care system in the Midwest until 2021.

In the midst of the public health crisis, former President Trump was downplaying the severity of the disease and was silencing officials from the Centers for Disease Control and Prevention, such as Nancy Messonier, who warned from the very beginning of the pandemic’s potential.

When the vaccines came out, the latent antivaccine movement flared up once again. And this time – unlike in decades past – the debate over vaccines had become partisan.

“Before the pandemic,” said Christopher Thomas, an emergency physician on the West Coast who requested that a pseudonym be used because of personal threats he has received, “patients wouldn’t really challenge me or throw out weird questions.” It’s not that he never encountered pushback, but the stakes felt lower, and people largely deferred to his medical expertise. “If we got a parent who had not vaccinated their child, I would totally engage back then,” Dr. Thomas said.

But the pandemic – and America’s response to it – changed the conversation. “The rhetoric ... switched from downplaying the virus to demonizing the vaccines,” Dr. Thomas said.
 

The toll on health care professionals

By the time vaccines were available, the public had begun to conflate doctors with public health experts, since both were “pushing” the vaccine.

“Most people probably don’t really know the difference between clinical medicine and public health,” said Richard Pan, MD, MPH, a pediatrician and California legislator who sponsored two bills – now laws – that strengthened state childhood vaccination requirements.

At first, it was clearly public health officials, such as Anthony Fauci, MD, who were the face of measures to mitigate the virus. But as doctors became the enforcers of those measures, the line between physicians and public health officials blurred.

A lot of the anger then shifted toward doctors, nurses, and other health care professionals, Dr. Pan said, “because we were, of course, the ones who would be administering the vaccines. They don’t really think of their doctor as a government person until your doctor is carrying a [government] message.”

Given the pressures and struggles of the past few years, it’s no surprise that burnout among health care professionals is high. According to an April 2023 study by the National Council of State Boards of Nursing and the National Forum of State Nursing Workforce Centers, an estimated 800,000 nurses expect to leave the profession by 2027, driven first and foremost by “stress and burnout.”

All of these departures in medicine’s “great resignation” have left hospitals and health care organizations even more short staffed, thereby increasing even more the pressure and burnout on those left.

The pandemic had already badly exacerbated the already widespread problem of burnout in the medical field, which Ms. Nelson said has contributed to the tension.

“The burnout problem that we have in health care is not a good basis for the development of a good therapeutic relationship,” Ms. Nelson said. “Burnout is fraught with apathy and desensitization to human emotions. It takes away the empathy that we once had for people that we see.”
 

What comes next?

Almost exactly 3 years after the world learned about SARS-CoV-2, Biden declared an end to the coronavirus public health emergency in April 2023. Yet, Americans continue to die from COVID, and the anger that bloomed and spread has not abated.

“I think we’re in a new steady state of violence in health care settings,” Ms. Nelson said. “It’s not gone down, because people are still very distressed.” That’s evident from the high prevalence of mental health conditions, the financial strain of first the pandemic and then inflation, and the overall traumatic impact the pandemic had on people, whether they recognize it or not.

The first step to solving any problem is, as the saying goes, to admit that there is a problem.

“I think people need to start stepping out of their comfort bubbles and start to look at things that make them uncomfortable,” Dr. Thomas said, but he doesn’t see that happening any time soon. “I’ve been very let down by physicians and embarrassed by the American physician organizations.”

The medical board in his state, he said, has stood by as some doctors continue misrepresenting medical evidence. “That’s been really, really hard on me. I didn’t think that the medical boards would go so far as to look the other way for something that was this tremendously bad.”

There are others who can take the lead – if they’re willing.

“There are some things the medical societies and academic health centers can do,” Dr. Hotez said, “starting with building up a culture of physicians and health care providers feeling comfortable in the public domain.” He said the messaging when he was getting his degrees was not to engage the public and not to talk to journalists because that was “self-promotion” or “grandstanding.” But the world is different now. Health care professionals need training in public engagement and communication, he said, and the culture needs to change so that health care providers feel comfortable speaking out without feeling “the sword of Damocles over their heads” every time they talk to a reporter, Dr. Hotez said.

There may be no silver bullet to solve the big-picture trust problem in medicine and public health. No TV appearance or quote in an article can solve it. But on an individual level — through careful relationship building with patients – doctors can strengthen that trust.

Telehealth may help with that, but there’s a fine balance there, Ms. Nelson cautioned. On the one hand, with the doctor and the patient each in their own private spaces, where they feel safe and comfortable, the overall experience can be more therapeutic and less stressful. At the same time, telehealth can pile on change-management tasks that can exacerbate burnout, “so it’s a delicate thing we have to approach.”

One very thin silver lining that could emerge from the way in which patients have begun to try to take charge of their care.

“They should fully understand the reasoning behind the recommendations that physicians are making,” Ms. Nelson said. “I’d like to see us get to a happy medium where it’s a partnership. We can’t go back to the old school where the doctor knows best and you don’t ever question him.

“What we need is the partnership, and I would love to see that as the silver lining, but the anger has got to settle down in order for that kind of productive thing to happen.”

As for the big picture? There’s a limit to what even society’s “miracle workers” can do. “The biggest priority right now for the health system is to protect their staff whatever way they can and do some training in deescalation,” Ms. Nelson said. “But I don’t think health care can solve the societal issues that seem to be creating this.”

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

A U.S. Food and Drug Administration investigation of injection-site necrosis in some people who received the 23-valent pneumococcal vaccine has concluded that the benefits of the vaccine outweigh the risks.

No similar safety signal has been detected for the more recently approved 15-valent and 20-valent pneumococcal conjugate vaccines, explain the investigators, led by Brendan Day, MD, MPH, from the FDA’s Center for Biologics Evaluation and Research, in their report published online in JAMA Internal Medicine.

Reports of injection-site necrosis emerged after the vaccine (Pneumovax 23, Merck) had been approved by the FDA and was administered to a large, diverse, real-world population.

Rare safety events can emerge after FDA approval, as clinical trials may not be able to detect them in a study-group population.

Therefore, “postmarketing safety surveillance is critical to further characterize the safety profile of licensed vaccines,” the investigators point out.

The FDA and the Centers for Disease Control and Prevention monitor the postmarketing safety of licensed vaccines using the Vaccine Adverse Event Reporting System (VAERS), which relies on people who get the vaccines to report adverse events.
 

Real-world finding

After reports indicated a safety signal in 2020, the researchers conducted a case-series review, calculated the reporting rate, and did a PubMed search for similar reports.

They found that the reporting rate for injection-site necrosis was less than 0.2 cases per 1 million vaccine doses administered. The PubMed search yielded two cases of injection-site necrosis after the vaccine.

The 23-valent vaccine helps protect people from pneumococcus bacterial infection. The manufacturer reports that it is for people at least 50 years of age and for children who are at least 2 years of age with medical conditions that put them at elevated risk for infection.

The U.S. package insert has been updated, in the Post-Marketing Experience section, to include injection-site necrosis.

Of the 104 VAERS reports identified by the researchers, 48 met the case definition. Of those cases, most were for skin necrosis (n = 43), five of which also included fat necrosis. The remaining five cases of necrosis affected fascia (n = 2); fat and fascia (n = 1); fat, fascia, and muscle (n = 1); and muscle (n = 1).

In 23 of the 48 cases (47.9%), the reactions were serious and included one death (unrelated to vaccination).

Seventeen patients (35.4%) were hospitalized and 26 (54.2%) required surgery, most commonly debridement. Eight patients (16.7%) underwent multiple surgical procedures and three (6.3%) required a skin graft.

For patients with skin necrosis (n = 43), the median age was 67 years, and most patients were female (n = 36). Twelve patients were immunocompromised.

Concomitant vaccinations were reported in 10 patients, five of whom got the shot in the same arm as the 23-valent pneumococcal vaccine. A concurrent diagnosis of cellulitis was reported in 16 patients and an abscess was reported in three patients. There were too few cases of fat, fascia, or muscle necrosis to draw conclusions, the researchers report.

Often, skin necrosis was seen after a progression of symptoms, such as redness, pain, or swelling.

“These reports are consistent with published descriptions of injection-site necrosis, which has been reported as a rare complication for many vaccines and injectable drugs,” the investigators report.

Although the researchers couldn’t conclude from the VAERS reports alone that the vaccine injection caused the necrosis, “the timing and the location of reactions at the injection site suggest a possible causal association with the vaccine,” they explain. However, they add, patient comorbidities and poor injection technique may also be contributors.

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

A U.S. Food and Drug Administration investigation of injection-site necrosis in some people who received the 23-valent pneumococcal vaccine has concluded that the benefits of the vaccine outweigh the risks.

No similar safety signal has been detected for the more recently approved 15-valent and 20-valent pneumococcal conjugate vaccines, explain the investigators, led by Brendan Day, MD, MPH, from the FDA’s Center for Biologics Evaluation and Research, in their report published online in JAMA Internal Medicine.

Reports of injection-site necrosis emerged after the vaccine (Pneumovax 23, Merck) had been approved by the FDA and was administered to a large, diverse, real-world population.

Rare safety events can emerge after FDA approval, as clinical trials may not be able to detect them in a study-group population.

Therefore, “postmarketing safety surveillance is critical to further characterize the safety profile of licensed vaccines,” the investigators point out.

The FDA and the Centers for Disease Control and Prevention monitor the postmarketing safety of licensed vaccines using the Vaccine Adverse Event Reporting System (VAERS), which relies on people who get the vaccines to report adverse events.
 

Real-world finding

After reports indicated a safety signal in 2020, the researchers conducted a case-series review, calculated the reporting rate, and did a PubMed search for similar reports.

They found that the reporting rate for injection-site necrosis was less than 0.2 cases per 1 million vaccine doses administered. The PubMed search yielded two cases of injection-site necrosis after the vaccine.

The 23-valent vaccine helps protect people from pneumococcus bacterial infection. The manufacturer reports that it is for people at least 50 years of age and for children who are at least 2 years of age with medical conditions that put them at elevated risk for infection.

The U.S. package insert has been updated, in the Post-Marketing Experience section, to include injection-site necrosis.

Of the 104 VAERS reports identified by the researchers, 48 met the case definition. Of those cases, most were for skin necrosis (n = 43), five of which also included fat necrosis. The remaining five cases of necrosis affected fascia (n = 2); fat and fascia (n = 1); fat, fascia, and muscle (n = 1); and muscle (n = 1).

In 23 of the 48 cases (47.9%), the reactions were serious and included one death (unrelated to vaccination).

Seventeen patients (35.4%) were hospitalized and 26 (54.2%) required surgery, most commonly debridement. Eight patients (16.7%) underwent multiple surgical procedures and three (6.3%) required a skin graft.

For patients with skin necrosis (n = 43), the median age was 67 years, and most patients were female (n = 36). Twelve patients were immunocompromised.

Concomitant vaccinations were reported in 10 patients, five of whom got the shot in the same arm as the 23-valent pneumococcal vaccine. A concurrent diagnosis of cellulitis was reported in 16 patients and an abscess was reported in three patients. There were too few cases of fat, fascia, or muscle necrosis to draw conclusions, the researchers report.

Often, skin necrosis was seen after a progression of symptoms, such as redness, pain, or swelling.

“These reports are consistent with published descriptions of injection-site necrosis, which has been reported as a rare complication for many vaccines and injectable drugs,” the investigators report.

Although the researchers couldn’t conclude from the VAERS reports alone that the vaccine injection caused the necrosis, “the timing and the location of reactions at the injection site suggest a possible causal association with the vaccine,” they explain. However, they add, patient comorbidities and poor injection technique may also be contributors.

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

A U.S. Food and Drug Administration investigation of injection-site necrosis in some people who received the 23-valent pneumococcal vaccine has concluded that the benefits of the vaccine outweigh the risks.

No similar safety signal has been detected for the more recently approved 15-valent and 20-valent pneumococcal conjugate vaccines, explain the investigators, led by Brendan Day, MD, MPH, from the FDA’s Center for Biologics Evaluation and Research, in their report published online in JAMA Internal Medicine.

Reports of injection-site necrosis emerged after the vaccine (Pneumovax 23, Merck) had been approved by the FDA and was administered to a large, diverse, real-world population.

Rare safety events can emerge after FDA approval, as clinical trials may not be able to detect them in a study-group population.

Therefore, “postmarketing safety surveillance is critical to further characterize the safety profile of licensed vaccines,” the investigators point out.

The FDA and the Centers for Disease Control and Prevention monitor the postmarketing safety of licensed vaccines using the Vaccine Adverse Event Reporting System (VAERS), which relies on people who get the vaccines to report adverse events.
 

Real-world finding

After reports indicated a safety signal in 2020, the researchers conducted a case-series review, calculated the reporting rate, and did a PubMed search for similar reports.

They found that the reporting rate for injection-site necrosis was less than 0.2 cases per 1 million vaccine doses administered. The PubMed search yielded two cases of injection-site necrosis after the vaccine.

The 23-valent vaccine helps protect people from pneumococcus bacterial infection. The manufacturer reports that it is for people at least 50 years of age and for children who are at least 2 years of age with medical conditions that put them at elevated risk for infection.

The U.S. package insert has been updated, in the Post-Marketing Experience section, to include injection-site necrosis.

Of the 104 VAERS reports identified by the researchers, 48 met the case definition. Of those cases, most were for skin necrosis (n = 43), five of which also included fat necrosis. The remaining five cases of necrosis affected fascia (n = 2); fat and fascia (n = 1); fat, fascia, and muscle (n = 1); and muscle (n = 1).

In 23 of the 48 cases (47.9%), the reactions were serious and included one death (unrelated to vaccination).

Seventeen patients (35.4%) were hospitalized and 26 (54.2%) required surgery, most commonly debridement. Eight patients (16.7%) underwent multiple surgical procedures and three (6.3%) required a skin graft.

For patients with skin necrosis (n = 43), the median age was 67 years, and most patients were female (n = 36). Twelve patients were immunocompromised.

Concomitant vaccinations were reported in 10 patients, five of whom got the shot in the same arm as the 23-valent pneumococcal vaccine. A concurrent diagnosis of cellulitis was reported in 16 patients and an abscess was reported in three patients. There were too few cases of fat, fascia, or muscle necrosis to draw conclusions, the researchers report.

Often, skin necrosis was seen after a progression of symptoms, such as redness, pain, or swelling.

“These reports are consistent with published descriptions of injection-site necrosis, which has been reported as a rare complication for many vaccines and injectable drugs,” the investigators report.

Although the researchers couldn’t conclude from the VAERS reports alone that the vaccine injection caused the necrosis, “the timing and the location of reactions at the injection site suggest a possible causal association with the vaccine,” they explain. However, they add, patient comorbidities and poor injection technique may also be contributors.

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

Choosing the right partner to add to your practice takes planning and strategic decision-making. When the match is right, the benefits can be significant: more hands to share the load of running a medical practice, and increased revenue and expanded patient population. A partner can bring in new, complementary strengths and skills. Adding a partner is also a way to prepare for the future by setting your practice up for a smooth transition if you or another partner is looking toward retirement.

But a mismatched partnership can cost you time and money, not to mention endless amount of conflict, dysfunction, and liability. Mutual trust and a long-term commitment on both sides are critical.

“Just like with marriage, it can be very difficult, traumatic, and expensive to break up with a partner,” said Clifton Straughn, MD, partner at Direct Access MD, a concierge-service model family practice in Anderson, S.C. “So, do your due diligence and take your time.” Picking the right partner is essential.
 

The basics

Before you begin the process of partnership with a physician, be sure you know what you need, the skill sets you’re looking for to complement your practice, and the personality characteristics and values that are important to you so the person you choose can check all the boxes and not just add a name to the letterhead.

“A lot of times, doctors go into this with just a general idea that they need more doctors or that they would like to be bigger or have more clout,” said Tim Boden, a certified medical practice executive with over 40 years of experience. “But you have to understand that to a certain degree, if you’re bringing somebody in who has basically an identical clinical profile to yours, you’re going to be sacrificing a bit of your lunch for a while until that person builds a name for himself or herself. A new partner’s skill set should match the need that you’re trying to fill.”

Figure out and discuss with your current partners how much it will cost to bring in a partner between their compensation and additional practice expenses. How much revenue will you expect the partner to generate? Will your practice break even the first year or the second? And how will you cover any shortfall?

It’s also essential to understand how the day-to-day operation of your practice will change after you add another partner.

• Will the new partner’s percentage of ownership be the same as that of the other partners?
• Will their ownership include a percentage of the facility, equipment, supplies, and accounts receivable?
• How will you split call and work hours?
• How will decision-making work?
• How would buyout work if a partner were to leave the practice, and is there a minimum obligation, such as a 5-year commitment?

As a team, you may also want to discuss “soft skills,” or the way you’d hope a partner would represent your practice to patients and the community.

“These can be harder to quantify,” said Dr. Straughn. “Evaluating them can take artful questions and simple observation over time.”
 

It’s a slow process

Many practices offer paths to partnership rather than bringing in a partner straight away. With this process, an incoming physician works toward that goal. If you’re going this route, discuss this during the hiring process, so that both sides are clear about the process. Rule No. 1 is to make sure that new hires understand that partnership is possible, although it’s not a given. The typical partnership track is 2-3 years, but you can set the timeline that works best for your practice.

Mr. Boden recommends at least a year for this period so as to allow you the opportunity to evaluate the new member, how they work, and how they fit with your team. The partnership track method is typically for young or fairly new physicians.

“I would avoid ever promising an ownership position to a recruit,” said Mr. Boden. “I would only show them how it can happen and what it would look like if they qualify.”
 

Consider professional help

If you want to be sure you weigh all the pros and cons of your new partner, a medical practice consultant may be the way to go. A consultant can identify many situations that you might overlook.

Some services offer a medical practice assessment to help you see where you need the most help and what skills might be best to bring to the table. They might also be able to take over some of the administrative work of a new hire if you like, so you and the other partners can focus solely on interacting with and observing the clinical abilities of a potential partner.

A health care attorney can help you build a sound agreement regarding decision-making and how the fees/costs will be divided and can put legal protections in place for everyone involved.

You’ll need a buy-sell agreement (also called a partnership or shareholder agreement) that spells out the terms and conditions, including buying into and selling out of the practice. A fair agreement respects all parties, while a poor one that offers the new partner a minority share or lessor profit may favor the practice’s current partners but could breed resentment, undermining the practice’s culture and morale.
 

Takeaway

Ideally, you’ll select someone with excellent credentials and experience with similar goals for the practice who blends well with your staff. It’s best to find someone who fits well culturally with your office and who practices medicine with a similar patient philosophy.

To that end, Mr. Boden encourages out-of-the-box questions for interviews, such as what a potential partner wants to make sure they have room for in their life, or what their ideal work and family life looks like. The more you can assess components such as emotional intelligence, =the fuller picture you’ll get.

“You’re going to be spending major hours every week with this person, and your destiny is going to be tied up with theirs to some degree,” said Mr. Boden. You can teach somebody the job, but if you don’t genuinely like and respect them and want to work with them daily, it may not be the right fit.

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

Choosing the right partner to add to your practice takes planning and strategic decision-making. When the match is right, the benefits can be significant: more hands to share the load of running a medical practice, and increased revenue and expanded patient population. A partner can bring in new, complementary strengths and skills. Adding a partner is also a way to prepare for the future by setting your practice up for a smooth transition if you or another partner is looking toward retirement.

But a mismatched partnership can cost you time and money, not to mention endless amount of conflict, dysfunction, and liability. Mutual trust and a long-term commitment on both sides are critical.

“Just like with marriage, it can be very difficult, traumatic, and expensive to break up with a partner,” said Clifton Straughn, MD, partner at Direct Access MD, a concierge-service model family practice in Anderson, S.C. “So, do your due diligence and take your time.” Picking the right partner is essential.
 

The basics

Before you begin the process of partnership with a physician, be sure you know what you need, the skill sets you’re looking for to complement your practice, and the personality characteristics and values that are important to you so the person you choose can check all the boxes and not just add a name to the letterhead.

“A lot of times, doctors go into this with just a general idea that they need more doctors or that they would like to be bigger or have more clout,” said Tim Boden, a certified medical practice executive with over 40 years of experience. “But you have to understand that to a certain degree, if you’re bringing somebody in who has basically an identical clinical profile to yours, you’re going to be sacrificing a bit of your lunch for a while until that person builds a name for himself or herself. A new partner’s skill set should match the need that you’re trying to fill.”

Figure out and discuss with your current partners how much it will cost to bring in a partner between their compensation and additional practice expenses. How much revenue will you expect the partner to generate? Will your practice break even the first year or the second? And how will you cover any shortfall?

It’s also essential to understand how the day-to-day operation of your practice will change after you add another partner.

• Will the new partner’s percentage of ownership be the same as that of the other partners?
• Will their ownership include a percentage of the facility, equipment, supplies, and accounts receivable?
• How will you split call and work hours?
• How will decision-making work?
• How would buyout work if a partner were to leave the practice, and is there a minimum obligation, such as a 5-year commitment?

As a team, you may also want to discuss “soft skills,” or the way you’d hope a partner would represent your practice to patients and the community.

“These can be harder to quantify,” said Dr. Straughn. “Evaluating them can take artful questions and simple observation over time.”
 

It’s a slow process

Many practices offer paths to partnership rather than bringing in a partner straight away. With this process, an incoming physician works toward that goal. If you’re going this route, discuss this during the hiring process, so that both sides are clear about the process. Rule No. 1 is to make sure that new hires understand that partnership is possible, although it’s not a given. The typical partnership track is 2-3 years, but you can set the timeline that works best for your practice.

Mr. Boden recommends at least a year for this period so as to allow you the opportunity to evaluate the new member, how they work, and how they fit with your team. The partnership track method is typically for young or fairly new physicians.

“I would avoid ever promising an ownership position to a recruit,” said Mr. Boden. “I would only show them how it can happen and what it would look like if they qualify.”
 

Consider professional help

If you want to be sure you weigh all the pros and cons of your new partner, a medical practice consultant may be the way to go. A consultant can identify many situations that you might overlook.

Some services offer a medical practice assessment to help you see where you need the most help and what skills might be best to bring to the table. They might also be able to take over some of the administrative work of a new hire if you like, so you and the other partners can focus solely on interacting with and observing the clinical abilities of a potential partner.

A health care attorney can help you build a sound agreement regarding decision-making and how the fees/costs will be divided and can put legal protections in place for everyone involved.

You’ll need a buy-sell agreement (also called a partnership or shareholder agreement) that spells out the terms and conditions, including buying into and selling out of the practice. A fair agreement respects all parties, while a poor one that offers the new partner a minority share or lessor profit may favor the practice’s current partners but could breed resentment, undermining the practice’s culture and morale.
 

Takeaway

Ideally, you’ll select someone with excellent credentials and experience with similar goals for the practice who blends well with your staff. It’s best to find someone who fits well culturally with your office and who practices medicine with a similar patient philosophy.

To that end, Mr. Boden encourages out-of-the-box questions for interviews, such as what a potential partner wants to make sure they have room for in their life, or what their ideal work and family life looks like. The more you can assess components such as emotional intelligence, =the fuller picture you’ll get.

“You’re going to be spending major hours every week with this person, and your destiny is going to be tied up with theirs to some degree,” said Mr. Boden. You can teach somebody the job, but if you don’t genuinely like and respect them and want to work with them daily, it may not be the right fit.

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

Choosing the right partner to add to your practice takes planning and strategic decision-making. When the match is right, the benefits can be significant: more hands to share the load of running a medical practice, and increased revenue and expanded patient population. A partner can bring in new, complementary strengths and skills. Adding a partner is also a way to prepare for the future by setting your practice up for a smooth transition if you or another partner is looking toward retirement.

But a mismatched partnership can cost you time and money, not to mention endless amount of conflict, dysfunction, and liability. Mutual trust and a long-term commitment on both sides are critical.

“Just like with marriage, it can be very difficult, traumatic, and expensive to break up with a partner,” said Clifton Straughn, MD, partner at Direct Access MD, a concierge-service model family practice in Anderson, S.C. “So, do your due diligence and take your time.” Picking the right partner is essential.
 

The basics

Before you begin the process of partnership with a physician, be sure you know what you need, the skill sets you’re looking for to complement your practice, and the personality characteristics and values that are important to you so the person you choose can check all the boxes and not just add a name to the letterhead.

“A lot of times, doctors go into this with just a general idea that they need more doctors or that they would like to be bigger or have more clout,” said Tim Boden, a certified medical practice executive with over 40 years of experience. “But you have to understand that to a certain degree, if you’re bringing somebody in who has basically an identical clinical profile to yours, you’re going to be sacrificing a bit of your lunch for a while until that person builds a name for himself or herself. A new partner’s skill set should match the need that you’re trying to fill.”

Figure out and discuss with your current partners how much it will cost to bring in a partner between their compensation and additional practice expenses. How much revenue will you expect the partner to generate? Will your practice break even the first year or the second? And how will you cover any shortfall?

It’s also essential to understand how the day-to-day operation of your practice will change after you add another partner.

• Will the new partner’s percentage of ownership be the same as that of the other partners?
• Will their ownership include a percentage of the facility, equipment, supplies, and accounts receivable?
• How will you split call and work hours?
• How will decision-making work?
• How would buyout work if a partner were to leave the practice, and is there a minimum obligation, such as a 5-year commitment?

As a team, you may also want to discuss “soft skills,” or the way you’d hope a partner would represent your practice to patients and the community.

“These can be harder to quantify,” said Dr. Straughn. “Evaluating them can take artful questions and simple observation over time.”
 

It’s a slow process

Many practices offer paths to partnership rather than bringing in a partner straight away. With this process, an incoming physician works toward that goal. If you’re going this route, discuss this during the hiring process, so that both sides are clear about the process. Rule No. 1 is to make sure that new hires understand that partnership is possible, although it’s not a given. The typical partnership track is 2-3 years, but you can set the timeline that works best for your practice.

Mr. Boden recommends at least a year for this period so as to allow you the opportunity to evaluate the new member, how they work, and how they fit with your team. The partnership track method is typically for young or fairly new physicians.

“I would avoid ever promising an ownership position to a recruit,” said Mr. Boden. “I would only show them how it can happen and what it would look like if they qualify.”
 

Consider professional help

If you want to be sure you weigh all the pros and cons of your new partner, a medical practice consultant may be the way to go. A consultant can identify many situations that you might overlook.

Some services offer a medical practice assessment to help you see where you need the most help and what skills might be best to bring to the table. They might also be able to take over some of the administrative work of a new hire if you like, so you and the other partners can focus solely on interacting with and observing the clinical abilities of a potential partner.

A health care attorney can help you build a sound agreement regarding decision-making and how the fees/costs will be divided and can put legal protections in place for everyone involved.

You’ll need a buy-sell agreement (also called a partnership or shareholder agreement) that spells out the terms and conditions, including buying into and selling out of the practice. A fair agreement respects all parties, while a poor one that offers the new partner a minority share or lessor profit may favor the practice’s current partners but could breed resentment, undermining the practice’s culture and morale.
 

Takeaway

Ideally, you’ll select someone with excellent credentials and experience with similar goals for the practice who blends well with your staff. It’s best to find someone who fits well culturally with your office and who practices medicine with a similar patient philosophy.

To that end, Mr. Boden encourages out-of-the-box questions for interviews, such as what a potential partner wants to make sure they have room for in their life, or what their ideal work and family life looks like. The more you can assess components such as emotional intelligence, =the fuller picture you’ll get.

“You’re going to be spending major hours every week with this person, and your destiny is going to be tied up with theirs to some degree,” said Mr. Boden. You can teach somebody the job, but if you don’t genuinely like and respect them and want to work with them daily, it may not be the right fit.

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

In a test of one of the nation’s most restrictive laws limiting noncompete clauses in medicine, an Indiana pediatric critical-care physician is suing to stop his former hospital employer from controlling his future employment prospects.

David Lankford, DO, acknowledges that he signed a contract with the Lutheran Health Network that included a noncompete clause. However, he claims in a lawsuit filed July 5 in Allen County Superior Court that an Indiana law that took effect 4 days earlier nullifies the clause because he quit his job with cause. 

Indiana’s law is notable among states because if a physician terminates his/her job for cause, the noncompete may be considered unenforceable.

“When you have physicians who are unable to work in their community, it creates a barrier for access to care for patients,” Dr. Lankford said in an interview. “I’m fighting to decrease barriers and continue to have patients be able to see their doctors in their own hometown or their own county.”

Lutheran Health’s media relations department did not respond to requests for comment.
 

Noncompete clauses ‘extremely common’

Non-compete clauses – which typically restrict when and where employees can take future jobs – are common in physician contracts, Anu Murthy, JD, who reviews employee contracts for a firm called Contract Diagnostics, said in an interview.

However, the tide has been turning against them.

About a dozen states and the District of Columbia have enacted legislation to limit the use of noncompetes in employment contracts, and about half of states have pending legislation that could dilute noncompete clauses, Ms. Murthy said. In June, the state of New York sent a noncompete ban bill to the governor’s desk.

For more about state-by-state restrictions on noncompete clauses, check this chart.

In his lawsuit, Dr. Lankford said he was hired in 2017 to work at Lutheran Hospital in Fort Wayne.

Dr. Lankford signed an employee renewal contract in 2020 that included a noncompete clause; his attorneys declined to provide details about the clause because of confidentiality restrictions. 

In 2022, the lawsuit says, Lutheran Hospital told Dr. Lankford that he’d need to take on more work due to layoffs of pediatric hospitalists. His patient load subsequently grew by 4-5 times, and he quit as of Jan. 7, 2023. 

Dr. Lankford wrote that he found a new job at Parkview Regional Medical Center in Fort Wayne, but his former employer threatened to take action under the noncompete clause, and Parkview withdrew its offer.

Among other things, the new Indiana law says that the clauses are not enforceable “if physician terminates the physician’s employment for cause.”

The lawsuit asks for a judge to prevent Lutheran Health Network from enforcing the clause.
 

Impact on patients

The new Indiana law also bans noncompete clauses for primary care physicians. Kathleen A. DeLaney, JD, one of Dr. Lankford’s attorneys, said in an interview that this provision came about because rural legislators didn’t want to add to the challenges of attracting primary care doctors to move to their communities.  

State legislators have become less friendly to noncompete clauses in medicine because they’re wary of the negative effects on patients, Evan Starr, PhD, said in an interview. The clauses prevent doctors from taking new jobs where they could continue to treat their previous patients, said Dr. Starr, associate professor in the department of management and organization at the University of Maryland.

However, he said, hospitals are fighting to preserve the clauses, arguing that they provide a base of patients to physicians in return for their agreement not to go work for a competitor.

The legal landscape may change even more. The Federal Trade Commission has proposed banning the clauses nationally, and a decision is expected in 2024. However, it’s an election year, which may delay a decision, attorney Ms. Murthy said, “and there is also language in the proposed rule that could exempt nonprofit hospitals, which further complicates the issues.”

For now, Ms. Murthy said, “we are still seeing noncompetes and other restrictive covenants in almost every contract we review in all 50 states and across all specialties. We explicitly explain to every client that they should only sign the agreement with the expectation that their specific noncompete will be enforced as written. Large employer groups, including hospital systems, will likely fight any kind of restriction or dilution of noncompetes, and these types of legal challenges could be tied up in court for many years.”
 

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

In a test of one of the nation’s most restrictive laws limiting noncompete clauses in medicine, an Indiana pediatric critical-care physician is suing to stop his former hospital employer from controlling his future employment prospects.

David Lankford, DO, acknowledges that he signed a contract with the Lutheran Health Network that included a noncompete clause. However, he claims in a lawsuit filed July 5 in Allen County Superior Court that an Indiana law that took effect 4 days earlier nullifies the clause because he quit his job with cause. 

Indiana’s law is notable among states because if a physician terminates his/her job for cause, the noncompete may be considered unenforceable.

“When you have physicians who are unable to work in their community, it creates a barrier for access to care for patients,” Dr. Lankford said in an interview. “I’m fighting to decrease barriers and continue to have patients be able to see their doctors in their own hometown or their own county.”

Lutheran Health’s media relations department did not respond to requests for comment.
 

Noncompete clauses ‘extremely common’

Non-compete clauses – which typically restrict when and where employees can take future jobs – are common in physician contracts, Anu Murthy, JD, who reviews employee contracts for a firm called Contract Diagnostics, said in an interview.

However, the tide has been turning against them.

About a dozen states and the District of Columbia have enacted legislation to limit the use of noncompetes in employment contracts, and about half of states have pending legislation that could dilute noncompete clauses, Ms. Murthy said. In June, the state of New York sent a noncompete ban bill to the governor’s desk.

For more about state-by-state restrictions on noncompete clauses, check this chart.

In his lawsuit, Dr. Lankford said he was hired in 2017 to work at Lutheran Hospital in Fort Wayne.

Dr. Lankford signed an employee renewal contract in 2020 that included a noncompete clause; his attorneys declined to provide details about the clause because of confidentiality restrictions. 

In 2022, the lawsuit says, Lutheran Hospital told Dr. Lankford that he’d need to take on more work due to layoffs of pediatric hospitalists. His patient load subsequently grew by 4-5 times, and he quit as of Jan. 7, 2023. 

Dr. Lankford wrote that he found a new job at Parkview Regional Medical Center in Fort Wayne, but his former employer threatened to take action under the noncompete clause, and Parkview withdrew its offer.

Among other things, the new Indiana law says that the clauses are not enforceable “if physician terminates the physician’s employment for cause.”

The lawsuit asks for a judge to prevent Lutheran Health Network from enforcing the clause.
 

Impact on patients

The new Indiana law also bans noncompete clauses for primary care physicians. Kathleen A. DeLaney, JD, one of Dr. Lankford’s attorneys, said in an interview that this provision came about because rural legislators didn’t want to add to the challenges of attracting primary care doctors to move to their communities.  

State legislators have become less friendly to noncompete clauses in medicine because they’re wary of the negative effects on patients, Evan Starr, PhD, said in an interview. The clauses prevent doctors from taking new jobs where they could continue to treat their previous patients, said Dr. Starr, associate professor in the department of management and organization at the University of Maryland.

However, he said, hospitals are fighting to preserve the clauses, arguing that they provide a base of patients to physicians in return for their agreement not to go work for a competitor.

The legal landscape may change even more. The Federal Trade Commission has proposed banning the clauses nationally, and a decision is expected in 2024. However, it’s an election year, which may delay a decision, attorney Ms. Murthy said, “and there is also language in the proposed rule that could exempt nonprofit hospitals, which further complicates the issues.”

For now, Ms. Murthy said, “we are still seeing noncompetes and other restrictive covenants in almost every contract we review in all 50 states and across all specialties. We explicitly explain to every client that they should only sign the agreement with the expectation that their specific noncompete will be enforced as written. Large employer groups, including hospital systems, will likely fight any kind of restriction or dilution of noncompetes, and these types of legal challenges could be tied up in court for many years.”
 

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

In a test of one of the nation’s most restrictive laws limiting noncompete clauses in medicine, an Indiana pediatric critical-care physician is suing to stop his former hospital employer from controlling his future employment prospects.

David Lankford, DO, acknowledges that he signed a contract with the Lutheran Health Network that included a noncompete clause. However, he claims in a lawsuit filed July 5 in Allen County Superior Court that an Indiana law that took effect 4 days earlier nullifies the clause because he quit his job with cause. 

Indiana’s law is notable among states because if a physician terminates his/her job for cause, the noncompete may be considered unenforceable.

“When you have physicians who are unable to work in their community, it creates a barrier for access to care for patients,” Dr. Lankford said in an interview. “I’m fighting to decrease barriers and continue to have patients be able to see their doctors in their own hometown or their own county.”

Lutheran Health’s media relations department did not respond to requests for comment.
 

Noncompete clauses ‘extremely common’

Non-compete clauses – which typically restrict when and where employees can take future jobs – are common in physician contracts, Anu Murthy, JD, who reviews employee contracts for a firm called Contract Diagnostics, said in an interview.

However, the tide has been turning against them.

About a dozen states and the District of Columbia have enacted legislation to limit the use of noncompetes in employment contracts, and about half of states have pending legislation that could dilute noncompete clauses, Ms. Murthy said. In June, the state of New York sent a noncompete ban bill to the governor’s desk.

For more about state-by-state restrictions on noncompete clauses, check this chart.

In his lawsuit, Dr. Lankford said he was hired in 2017 to work at Lutheran Hospital in Fort Wayne.

Dr. Lankford signed an employee renewal contract in 2020 that included a noncompete clause; his attorneys declined to provide details about the clause because of confidentiality restrictions. 

In 2022, the lawsuit says, Lutheran Hospital told Dr. Lankford that he’d need to take on more work due to layoffs of pediatric hospitalists. His patient load subsequently grew by 4-5 times, and he quit as of Jan. 7, 2023. 

Dr. Lankford wrote that he found a new job at Parkview Regional Medical Center in Fort Wayne, but his former employer threatened to take action under the noncompete clause, and Parkview withdrew its offer.

Among other things, the new Indiana law says that the clauses are not enforceable “if physician terminates the physician’s employment for cause.”

The lawsuit asks for a judge to prevent Lutheran Health Network from enforcing the clause.
 

Impact on patients

The new Indiana law also bans noncompete clauses for primary care physicians. Kathleen A. DeLaney, JD, one of Dr. Lankford’s attorneys, said in an interview that this provision came about because rural legislators didn’t want to add to the challenges of attracting primary care doctors to move to their communities.  

State legislators have become less friendly to noncompete clauses in medicine because they’re wary of the negative effects on patients, Evan Starr, PhD, said in an interview. The clauses prevent doctors from taking new jobs where they could continue to treat their previous patients, said Dr. Starr, associate professor in the department of management and organization at the University of Maryland.

However, he said, hospitals are fighting to preserve the clauses, arguing that they provide a base of patients to physicians in return for their agreement not to go work for a competitor.

The legal landscape may change even more. The Federal Trade Commission has proposed banning the clauses nationally, and a decision is expected in 2024. However, it’s an election year, which may delay a decision, attorney Ms. Murthy said, “and there is also language in the proposed rule that could exempt nonprofit hospitals, which further complicates the issues.”

For now, Ms. Murthy said, “we are still seeing noncompetes and other restrictive covenants in almost every contract we review in all 50 states and across all specialties. We explicitly explain to every client that they should only sign the agreement with the expectation that their specific noncompete will be enforced as written. Large employer groups, including hospital systems, will likely fight any kind of restriction or dilution of noncompetes, and these types of legal challenges could be tied up in court for many years.”
 

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

The U.S. Food and Drug Administration has approved an injectable monoclonal antibody to protect newborns and infants against respiratory syncytial virus (RSV).

The monoclonal antibody Beyfortus (nirsevimab-alip), which already is approved for use in Europe and Canada, is indicated for newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who are vulnerable to severe RSV through their second RSV season.

As many as 80,000 children under age 5 years are hospitalized with an RSV infection annually in the United States. Most cases are mild, but infants under 6 months, those born prematurely, and children with weakened immune systems or neuromuscular disorders are at an increased risk for severe illness, according to the Centers for Disease Control and Prevention.

The highly contagious virus is also a concern for immunocompromised adults and older people with underlying health conditions, who are at increased risk for severe disease.

Sanofi and AstraZeneca, which jointly developed the injectable agent, said in a press release that the companies plan to make it available by the fall of 2023. The long-acting antibody is given as a single intramuscular injection.

Beyfortus was approved in part based on data from the phase 3 MELODY trial, which found the shot reduced the incidence of medically attended lower respiratory tract infections associated with RSV by 74.9% versus placebo (95% confidence interval, 50.6-87.3; P < .001).

The phase 2/3 MEDLEY trial, conducted between July 2019 and May 2021, compared Beyfortus with palivizumab, another RSV antibody injection with more limited indications. The trial included more than 900 preterm infants less than 35 weeks’ gestational age and infants with congenital heart disease. Results were similar to the phase 3 MELODY trial, according to the manufacturers.

“Today’s approval marks an unprecedented moment for protecting infant health in the United States, following an RSV season that took a record toll on infants, their families, and the U.S. health care system,” said Thomas Triomphe, executive vice president for vaccines at Sanofi, in a press release about the FDA decision. “Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season.”

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

The U.S. Food and Drug Administration has approved an injectable monoclonal antibody to protect newborns and infants against respiratory syncytial virus (RSV).

The monoclonal antibody Beyfortus (nirsevimab-alip), which already is approved for use in Europe and Canada, is indicated for newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who are vulnerable to severe RSV through their second RSV season.

As many as 80,000 children under age 5 years are hospitalized with an RSV infection annually in the United States. Most cases are mild, but infants under 6 months, those born prematurely, and children with weakened immune systems or neuromuscular disorders are at an increased risk for severe illness, according to the Centers for Disease Control and Prevention.

The highly contagious virus is also a concern for immunocompromised adults and older people with underlying health conditions, who are at increased risk for severe disease.

Sanofi and AstraZeneca, which jointly developed the injectable agent, said in a press release that the companies plan to make it available by the fall of 2023. The long-acting antibody is given as a single intramuscular injection.

Beyfortus was approved in part based on data from the phase 3 MELODY trial, which found the shot reduced the incidence of medically attended lower respiratory tract infections associated with RSV by 74.9% versus placebo (95% confidence interval, 50.6-87.3; P < .001).

The phase 2/3 MEDLEY trial, conducted between July 2019 and May 2021, compared Beyfortus with palivizumab, another RSV antibody injection with more limited indications. The trial included more than 900 preterm infants less than 35 weeks’ gestational age and infants with congenital heart disease. Results were similar to the phase 3 MELODY trial, according to the manufacturers.

“Today’s approval marks an unprecedented moment for protecting infant health in the United States, following an RSV season that took a record toll on infants, their families, and the U.S. health care system,” said Thomas Triomphe, executive vice president for vaccines at Sanofi, in a press release about the FDA decision. “Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season.”

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

The U.S. Food and Drug Administration has approved an injectable monoclonal antibody to protect newborns and infants against respiratory syncytial virus (RSV).

The monoclonal antibody Beyfortus (nirsevimab-alip), which already is approved for use in Europe and Canada, is indicated for newborns and infants born during or entering their first RSV season, and for children up to 24 months of age who are vulnerable to severe RSV through their second RSV season.

As many as 80,000 children under age 5 years are hospitalized with an RSV infection annually in the United States. Most cases are mild, but infants under 6 months, those born prematurely, and children with weakened immune systems or neuromuscular disorders are at an increased risk for severe illness, according to the Centers for Disease Control and Prevention.

The highly contagious virus is also a concern for immunocompromised adults and older people with underlying health conditions, who are at increased risk for severe disease.

Sanofi and AstraZeneca, which jointly developed the injectable agent, said in a press release that the companies plan to make it available by the fall of 2023. The long-acting antibody is given as a single intramuscular injection.

Beyfortus was approved in part based on data from the phase 3 MELODY trial, which found the shot reduced the incidence of medically attended lower respiratory tract infections associated with RSV by 74.9% versus placebo (95% confidence interval, 50.6-87.3; P < .001).

The phase 2/3 MEDLEY trial, conducted between July 2019 and May 2021, compared Beyfortus with palivizumab, another RSV antibody injection with more limited indications. The trial included more than 900 preterm infants less than 35 weeks’ gestational age and infants with congenital heart disease. Results were similar to the phase 3 MELODY trial, according to the manufacturers.

“Today’s approval marks an unprecedented moment for protecting infant health in the United States, following an RSV season that took a record toll on infants, their families, and the U.S. health care system,” said Thomas Triomphe, executive vice president for vaccines at Sanofi, in a press release about the FDA decision. “Beyfortus is the only monoclonal antibody approved for passive immunization to provide safe and effective protection for all infants during their first RSV season.”

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

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

Feelings of inadequacy, in terms of skills and expectations in an ever-changing system, are common emotions that many doctors have experienced since the start of the pandemic.

COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.

Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
 

Doctors and burnout

Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.

These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
 

The impostor phenomenon

The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.

IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
 

Surveying IS

IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:

• Perfectionist: insecurity related to self-imposed, unachievable goals
• Expert: feeling inadequate from lacking sufficient knowledge
• Superperson: assuming excessive workloads just to feel okay among peers
• Natural genius: experiencing shame when it takes effort to develop a skill
• Soloist: believing that requesting help is a sign of weakness

Risk factors

Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.

Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
 

Impact on doctors

Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.

A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.

Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.

With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.

The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
 

Lessening the impact

An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.

• Review and celebrate feats that have led to your professional role.
• Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
• Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
• Exercise self-compassion as an alternative to relying on an external locus of self-worth.
• Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Feelings of inadequacy, in terms of skills and expectations in an ever-changing system, are common emotions that many doctors have experienced since the start of the pandemic.

COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.

Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
 

Doctors and burnout

Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.

These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
 

The impostor phenomenon

The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.

IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
 

Surveying IS

IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:

• Perfectionist: insecurity related to self-imposed, unachievable goals
• Expert: feeling inadequate from lacking sufficient knowledge
• Superperson: assuming excessive workloads just to feel okay among peers
• Natural genius: experiencing shame when it takes effort to develop a skill
• Soloist: believing that requesting help is a sign of weakness

Risk factors

Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.

Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
 

Impact on doctors

Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.

A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.

Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.

With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.

The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
 

Lessening the impact

An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.

• Review and celebrate feats that have led to your professional role.
• Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
• Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
• Exercise self-compassion as an alternative to relying on an external locus of self-worth.
• Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Feelings of inadequacy, in terms of skills and expectations in an ever-changing system, are common emotions that many doctors have experienced since the start of the pandemic.

COVID-19 imposed challenges on health care professionals and systems by forcing changes in how doctors organize themselves professionally as well as in their relationships with patients and in their expectations (realistic or not) of their roles. The situation was bound to generate high rates of frustration and discomfort among younger and older physicians. It was compounded by a generational transition of the profession, which was accelerated by the virus. It was not managed by the decision-makers and was painful for doctors and patients.

Impostor syndrome (IS) is a psychological construct characterized by the persistent belief that one’s success is undeserved, rather than stemming from personal effort, skill, and ability. The phenomenon is common among medics for various reasons, including professional burnout. Recent studies have helped to better define the extent and characteristic features of the syndrome, as well as efforts to combat it.
 

Doctors and burnout

Although occupational burnout among physicians is a systemic issue primarily attributable to problems in the practice environment, professional norms and aspects of medical culture often contribute to the distress that individual physicians experience.

These dimensions have been well characterized and include suggestions that physicians should be impervious to normal human limitations (that is, superhuman), that work should always come first, and that seeking help is a sign of weakness. In aggregate, these attitudes lead many physicians to engage in unhealthy levels of self-sacrifice, manifested by excessive work hours, anxiety about missing something that would benefit their patients, and prioritizing work over personal health. These factors are familiar to many hospital-based and family physicians.
 

The impostor phenomenon

The impostor phenomenon (IP) is a psychological experience of intellectual and professional fraud. Individuals who suffer from it believe that others have inflated perceptions of the individual’s abilities and fear being judged. This fear persists despite continual proof of the individual’s successes. These people ignore praise, are highly self-critical, and attribute their successes to external factors, such as luck, hard work, or receiving help from others, rather than to qualities such as skill, intelligence, or ability.

IP is common among men and women. Some studies suggest it may be more prevalent among women. Studies across industries suggest that the phenomenon is associated with personal consequences (for example, low emotional well-being, problems with work-life integration, anxiety, depression, suicide) and professional consequences (for example, impaired job performance, occupational burnout). Studies involving U.S. medical students have revealed that more than one in four medical students experience IP and that those who experience it are at higher risk for burnout.
 

Surveying IS

IS, which is not a formal psychiatric diagnosis, is defined as having feelings of uncertainty, inadequacy, and being undeserving of one’s achievements despite evidence to the contrary. There are five subtypes of IS:

• Perfectionist: insecurity related to self-imposed, unachievable goals
• Expert: feeling inadequate from lacking sufficient knowledge
• Superperson: assuming excessive workloads just to feel okay among peers
• Natural genius: experiencing shame when it takes effort to develop a skill
• Soloist: believing that requesting help is a sign of weakness

Risk factors

Studies suggest that IS is a problem early in the physician training process. There is limited information on IS among physicians in practice.

Because transitions represent a risk factor for IP, the frequent rotation between clerkships and being a “perpetual novice” during medical school training may contribute to the high prevalence. Qualitative studies suggest that, once in practice, other professional experiences (for example, unfavorable patient outcomes, patient complaints, rejection of grants or manuscripts, and poor teaching evaluations or patient satisfaction scores) may contribute to IP.
 

Impact on doctors

Several methods have been used to classify how much the phenomenon interferes with a person’s life. The Clance Impostor Phenomenon Scale is a 20-item scale that asks respondents to indicate how well each item characterizes their experience on a 5-point scale. Options range from “not at all” to “very true.” The sum of responses to the individual items is used to create an aggregate score (IP score). The higher the score, the more frequently and seriously IP interferes with a person’s life.

A simplified version of the IP score was used in a study of 3,237 U.S. doctors that investigated the association between IS and burnout among doctors and to compare their rates of IS with those of other professionals.

Mean IP scores were higher for female physicians than for male physicians (mean, 10.91 vs. 9.12; P < .001). Scores decreased with age and were lower among those who were married or widowed.

With respect to professional characteristics, IP scores were greater among those in academic practice or who worked in the Veterans Affairs medical system and decreased with years in practice.

The highest IP scores were among pediatric subspecialists, general pediatricians, and emergency medicine physicians. Scores were lowest among ophthalmologists, radiologists, and orthopedic surgeons. IP has been independently associated with the risk of burnout and low professional fulfillment.
 

Lessening the impact

An article commenting on the study highlighted the following expert practice strategies that doctors can use to reduce the impact of IS in their professional life.

• Review and celebrate feats that have led to your professional role.
• Share concerns with trusted colleagues who can validate your accomplishments and normalize your feelings by reporting their own struggles with IS.
• Combat perfectionism by accepting that it is okay to be good enough when meeting the challenges of a demanding profession.
• Exercise self-compassion as an alternative to relying on an external locus of self-worth.
• Understand that IS may be common, especially during transitions, such as when entering medical school, graduate medical training, or starting a new career.

This article was translated from Univadis Italy. A version appeared on Medscape.com.

Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.

Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.

Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.

The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.

The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.

Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
 

Findings clarify clinical practice guidelines

“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.

“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.

However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.

“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.

The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.

Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.

Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.

Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.

Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.

The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.

The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.

Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
 

Findings clarify clinical practice guidelines

“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.

“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.

However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.

“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.

The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.

Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.

Use of inhalers with long-acting muscarinic antagonists and long-acting beta-agonists reduced COPD exacerbations and pneumonia hospitalizations compared with inhalers with corticosteroids and long-acting beta-agonists, based on data from more than 30,000 individuals.

Current clinical guidelines for chronic obstructive pulmonary disease (COPD) patients recommend inhalers with long-acting muscarinic antagonists (LAMAs) and long-acting beta-agonists (LABAs) over those with inhaled corticosteroids (ICSs) and LABAs, but data comparing the two formulations have been inconsistent, and concerns about generalizability persist, wrote William B. Feldman, MD, of Brigham and Women’s Hospital, Boston, and colleagues.

In a study published in JAMA Internal Medicine, the researchers reviewed data from a commercial insurance claims database of individuals diagnosed with COPD who filled a new prescription for a LAMA-LABA inhaler or ICS-LABA inhaler between Jan. 1, 2014, and Dec. 31, 2019. Patients with asthma and those younger than 40 years were excluded. The study population included 137,833 individuals with a mean age of 70.2 years; 50.4% were female. Of the 107,004 ICS-LABA users and 30,829 LAMA-LABA users, 30,216 matched pairs were included in a 1:1 propensity score matched study. The primary outcomes were effectiveness, based on the rate of first moderate or severe COPD exacerbation, and safety, based on the rate of first pneumonia hospitalization.

Use of LAMA-LABA inhalers was associated with an 8% reduction in the rate of first moderate or severe COPD exacerbation and a 20% reduction in the rate of first pneumonia hospitalization compared with use of ICS-LABA (hazard ratios 0.92 and 0.80, respectively). The absolute rate reductions with LAMA-LABA inhalers for first moderate or severe COPD exacerbations and for first pneumonia hospitalizations were was 43.0 events per 1,000 person-years and 91.8 events per person-years, respectively.

The overall rates of total moderate to severe COPD and pneumonia hospitalizations were 5% and 17% lower, respectively, among patients who used LAMA-LABA than those treated with ICS-LABA. The results were consistently robust in subgroup and sensitivity analyses, the researchers wrote in their discussion. However, the results must be interpreted cautiously in comparison to other large studies because of the significant differences in the cohorts of patients studied, notably that most patients in the current study had no received previous inhaler therapy.

The study findings were limited by several factors including the relatively short follow-up time and reliance on prescription fills as an indicator of medication use, the researchers noted. Other limitations included notable differences between the LAMA-LABA patients and ICS-LABA patients, such as more severe COPD and less access to respiratory care, they wrote.

Although the current study is not the definitive answer to conflicting results from previous trials, it is the largest know to date to compare LAMA-LABA with ICS-LABA, and the results support LAMA-LABA as the preferred therapy for COPD patients, the researchers concluded.
 

Findings clarify clinical practice guidelines

“This study was required to provide clarity regarding the optimal choice of treatment for COPD given conflicting data from other recent trials,” Suman Pal, MBBS, of the University of New Mexico, Albuquerque, said in an interview.

“The study findings reinforce the benefits of combined LAMA-LABA in improving clinical outcomes in COPD in a real-world setting,” and the data provide further support for choosing LAMA-LABA over ICS-LABA in COPD patients, said Dr. Pal, who was not involved in the study.

However, availability and affordability of LAMA-LABA inhalers may be barriers to expanding their use in clinical practice, he noted.

“Additional research is needed to accurately define which patient populations would benefit most from the therapy and whether patients who have previously been stabilized on ICS-LABA would derive additional benefit from a change in therapy,” Dr. Pal said.

The study was supported by the National Heart, Lung, and Blood Institute and funding from the Commonwealth Fund and Arnold Ventures.

Dr. Feldman disclosed receiving personal fees from Alosa Health and Aetion, serving as an expert witness in litigation against inhaler manufacturers, and receiving an honorarium for a presentation to Blue Cross Blue Shield of Massachusetts unrelated to the current study. Dr. Pal had no financial conflicts to disclose.