Clinical Psychiatry News

TOPLINE:

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

METHODOLOGY: 

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

TAKEAWAY: 

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY: 

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

TAKEAWAY: 

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

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

METHODOLOGY: 

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

TAKEAWAY: 

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

IN PRACTICE:

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

SOURCE:

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

LIMITATIONS:

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

DISCLOSURES:

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

Pauline Anderson has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

Screening for Allergies

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

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

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

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


 

Signs of Dysautonomia, Joint Hypermobility

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

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

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

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

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

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

Depression, Anxiety, and Female Patients

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

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

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

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

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

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


 

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

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

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

Narrowing the Information Gap

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

Screening for Allergies

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

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

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

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


 

Signs of Dysautonomia, Joint Hypermobility

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

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

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

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

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

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

Depression, Anxiety, and Female Patients

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

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

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

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

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

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


 

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

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

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

Narrowing the Information Gap

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

Screening for Allergies

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

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

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

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


 

Signs of Dysautonomia, Joint Hypermobility

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

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

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

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

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

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

Depression, Anxiety, and Female Patients

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

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

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

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

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

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


 

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

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

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

Narrowing the Information Gap

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Reasons for Recovery

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

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

Where Research Is Headed

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Reasons for Recovery

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

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

Where Research Is Headed

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Reasons for Recovery

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

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

Where Research Is Headed

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

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

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

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

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

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

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

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

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

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

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

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

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

In a victory for clinicians who fought to keep working regardless of age, a San Diego–based medical group has agreed to settle a federal investigation by paying nearly $7 million to physicians subject to their employer’s policy requiring them to quit at age 75.

In a statement, the US Equal Employment Opportunity Commission (EEOC) said the settlement will resolve an age and disability discrimination charge filed against Scripps Clinic Medical Group. The medical group is part of Scripps Health, a major provider of medical services in the San Diego region that operates five local hospitals.

The EECO said it found “reasonable cause” that the medical group violated the Age Discrimination in Employment Act and the Americans with Disabilities Act.

US health systems are facing lawsuits that claim they’ve engaged in age discrimination by requiring physicians to take cognitive tests when they reach specific ages.

The Scripps medical group’s mandatory retirement policy began in 2016 and was consistent with California law, which specifically allows for mandatory retirement of physicians in medical groups at age 70, Scripps said in a statement, adding that it rescinded the policy in 2018.

“This policy was put in place to enhance patient safety,” Scripps said. “The EEOC took the position while such a policy is expressly legal under California law; it is not allowed under federal law.”

The Federal Age Discrimination in Employment Act, passed in 1967, states that employers may not “fail or refuse to hire or to discharge any individual or otherwise discriminate against any individual with respect to his compensation, terms, conditions, or privileges of employment because of such individual’s age.” There are exceptions, however, in cases of public safety for professions such as air traffic controllers.

California law has a similar provision banning age discrimination, but it makes an exception for “any employee who has attained 70 years of age and is a physician employed by a professional medical corporation, the articles or bylaws of which provide for compulsory retirement.”

In 2020, an estimated 12% of US licensed physicians were at least 70 years old — more than 120,000 in total — up from 9% in a 2010, according to a Federation of State Medical Boards 2021 report.

Scripps Clinic Medical Group settled with the EEOC “without any admission of fault or wrongdoing to avoid the continued expense and distraction of litigation,” its statement said. It agreed to pay $6.875 million to the affected physicians.

When asked about how many physicians were affected by the policy, a Scripps human resources official said, “this was disputed but very few. The policy was only in effect for 2 years, 2016 and 2017. Additionally, by age 75, most doctors have retired. And those who have not almost always have voluntarily limited their practice.”

The Scripps official didn’t respond to questions about the number of patients served by the medical group and how many physicians it employs.

According to the EEOC, the medical group has agreed to tell employees that the policy has been scrapped and must “clarify that the company does not have any policy in which age is a factor in making employment decisions, including termination, retirement, and terms and conditions of employment.”

Scripps Clinic Medical Group also agreed to require division and department heads, executive leadership, and human resources employees to be trained regarding the Age Discrimination in Employment Act and the Americans with Disabilities Act.

A version of this article appeared on Medscape.com.

In a victory for clinicians who fought to keep working regardless of age, a San Diego–based medical group has agreed to settle a federal investigation by paying nearly $7 million to physicians subject to their employer’s policy requiring them to quit at age 75.

In a statement, the US Equal Employment Opportunity Commission (EEOC) said the settlement will resolve an age and disability discrimination charge filed against Scripps Clinic Medical Group. The medical group is part of Scripps Health, a major provider of medical services in the San Diego region that operates five local hospitals.

The EECO said it found “reasonable cause” that the medical group violated the Age Discrimination in Employment Act and the Americans with Disabilities Act.

US health systems are facing lawsuits that claim they’ve engaged in age discrimination by requiring physicians to take cognitive tests when they reach specific ages.

The Scripps medical group’s mandatory retirement policy began in 2016 and was consistent with California law, which specifically allows for mandatory retirement of physicians in medical groups at age 70, Scripps said in a statement, adding that it rescinded the policy in 2018.

“This policy was put in place to enhance patient safety,” Scripps said. “The EEOC took the position while such a policy is expressly legal under California law; it is not allowed under federal law.”

The Federal Age Discrimination in Employment Act, passed in 1967, states that employers may not “fail or refuse to hire or to discharge any individual or otherwise discriminate against any individual with respect to his compensation, terms, conditions, or privileges of employment because of such individual’s age.” There are exceptions, however, in cases of public safety for professions such as air traffic controllers.

California law has a similar provision banning age discrimination, but it makes an exception for “any employee who has attained 70 years of age and is a physician employed by a professional medical corporation, the articles or bylaws of which provide for compulsory retirement.”

In 2020, an estimated 12% of US licensed physicians were at least 70 years old — more than 120,000 in total — up from 9% in a 2010, according to a Federation of State Medical Boards 2021 report.

Scripps Clinic Medical Group settled with the EEOC “without any admission of fault or wrongdoing to avoid the continued expense and distraction of litigation,” its statement said. It agreed to pay $6.875 million to the affected physicians.

When asked about how many physicians were affected by the policy, a Scripps human resources official said, “this was disputed but very few. The policy was only in effect for 2 years, 2016 and 2017. Additionally, by age 75, most doctors have retired. And those who have not almost always have voluntarily limited their practice.”

The Scripps official didn’t respond to questions about the number of patients served by the medical group and how many physicians it employs.

According to the EEOC, the medical group has agreed to tell employees that the policy has been scrapped and must “clarify that the company does not have any policy in which age is a factor in making employment decisions, including termination, retirement, and terms and conditions of employment.”

Scripps Clinic Medical Group also agreed to require division and department heads, executive leadership, and human resources employees to be trained regarding the Age Discrimination in Employment Act and the Americans with Disabilities Act.

A version of this article appeared on Medscape.com.

In a victory for clinicians who fought to keep working regardless of age, a San Diego–based medical group has agreed to settle a federal investigation by paying nearly $7 million to physicians subject to their employer’s policy requiring them to quit at age 75.

In a statement, the US Equal Employment Opportunity Commission (EEOC) said the settlement will resolve an age and disability discrimination charge filed against Scripps Clinic Medical Group. The medical group is part of Scripps Health, a major provider of medical services in the San Diego region that operates five local hospitals.

The EECO said it found “reasonable cause” that the medical group violated the Age Discrimination in Employment Act and the Americans with Disabilities Act.

US health systems are facing lawsuits that claim they’ve engaged in age discrimination by requiring physicians to take cognitive tests when they reach specific ages.

The Scripps medical group’s mandatory retirement policy began in 2016 and was consistent with California law, which specifically allows for mandatory retirement of physicians in medical groups at age 70, Scripps said in a statement, adding that it rescinded the policy in 2018.

“This policy was put in place to enhance patient safety,” Scripps said. “The EEOC took the position while such a policy is expressly legal under California law; it is not allowed under federal law.”

The Federal Age Discrimination in Employment Act, passed in 1967, states that employers may not “fail or refuse to hire or to discharge any individual or otherwise discriminate against any individual with respect to his compensation, terms, conditions, or privileges of employment because of such individual’s age.” There are exceptions, however, in cases of public safety for professions such as air traffic controllers.

California law has a similar provision banning age discrimination, but it makes an exception for “any employee who has attained 70 years of age and is a physician employed by a professional medical corporation, the articles or bylaws of which provide for compulsory retirement.”

In 2020, an estimated 12% of US licensed physicians were at least 70 years old — more than 120,000 in total — up from 9% in a 2010, according to a Federation of State Medical Boards 2021 report.

Scripps Clinic Medical Group settled with the EEOC “without any admission of fault or wrongdoing to avoid the continued expense and distraction of litigation,” its statement said. It agreed to pay $6.875 million to the affected physicians.

When asked about how many physicians were affected by the policy, a Scripps human resources official said, “this was disputed but very few. The policy was only in effect for 2 years, 2016 and 2017. Additionally, by age 75, most doctors have retired. And those who have not almost always have voluntarily limited their practice.”

The Scripps official didn’t respond to questions about the number of patients served by the medical group and how many physicians it employs.

According to the EEOC, the medical group has agreed to tell employees that the policy has been scrapped and must “clarify that the company does not have any policy in which age is a factor in making employment decisions, including termination, retirement, and terms and conditions of employment.”

Scripps Clinic Medical Group also agreed to require division and department heads, executive leadership, and human resources employees to be trained regarding the Age Discrimination in Employment Act and the Americans with Disabilities Act.

A version of this article appeared on Medscape.com.

Delusions of parasitosis is linked to female gender, older age, polypharmacy with more than five drugs, and certain types of drugs (attention-deficit/hyperactivity disorder drugs, selective serotonin reuptake inhibitors, gabapentin, and opioids), reported researchers in a small retrospective case-control study.

Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.

“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”

To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.

Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).

In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”

They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.

“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.

Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.

Dr. Rieder

“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”

The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.

Delusions of parasitosis is linked to female gender, older age, polypharmacy with more than five drugs, and certain types of drugs (attention-deficit/hyperactivity disorder drugs, selective serotonin reuptake inhibitors, gabapentin, and opioids), reported researchers in a small retrospective case-control study.

Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.

“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”

To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.

Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).

In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”

They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.

“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.

Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.

Dr. Rieder

“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”

The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.

Delusions of parasitosis is linked to female gender, older age, polypharmacy with more than five drugs, and certain types of drugs (attention-deficit/hyperactivity disorder drugs, selective serotonin reuptake inhibitors, gabapentin, and opioids), reported researchers in a small retrospective case-control study.

Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.

“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”

To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.

Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).

In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”

They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.

“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.

Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.

Dr. Rieder

“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”

The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

‘Twas the night before Festivus and all through the house, everyone was griping.

In case you’ve only been watching Friends reruns lately, Festivus is a holiday that originated 25 years ago in the last season of Seinfeld. George’s father created it as an alternative to Christmas hype. In addition to an aluminum pole, the holiday features the annual airing of grievances, when one is encouraged to voice complaints. Aluminum poles haven’t replaced Christmas trees, but the spirit of Festivus is still with us in the widespread airing of grievances in 2023.

Kaiser Permanente

Complaining isn’t just a post-pandemic problem. Hector spends quite a bit of time complaining about Paris in the Iliad. That was a few pandemics ago. And repining is ubiquitous in literature — as human as walking on two limbs it seems. Ostensibly, we complain to effect change: Something is wrong and we expect it to be different. But that’s not the whole story. No one believes the weather will improve or the Patriots will play better because we complain about them. So why do we bother?

Even if nothing changes on the outside, it does seem to alter our internal state, serving a healthy psychological function. Putting to words what is aggravating can have the same benefit of deep breathing. We describe it as “getting something off our chest” because that’s what it feels like. We feel unburdened just by saying it out loud. Complaining is also a way to bond with others. We have a strong instinct to be with people like ourselves and what better way to connect than to find common suffering? Think about the last time you complained: Cranky staff, prior auths, Medicare, disrespectful patients, many of your colleagues will nod in agreement, validating your feelings and making you feel less isolated.

There are also maladaptive reasons for whining. It’s obviously an elementary way to get attention or to remove responsibility. It can also be a political weapon (office politics included). It’s such a potent way to connect that it’s used to build alliances and clout. “Washington is doing a great job,” said no candidate ever. No, if you want to get people on your side, find something irritating and complain to everyone how annoying it is. This solidifies “us” versus “them,” which can harm organizations and families alike.

Yet, eliminating all complaints is neither feasible, nor probably advisable. You could try to make your office a complaint-free zone, but the likely result would be to push any griping to the remote corners where you can no longer hear them. These criticisms might have uncovered missed opportunities, identify problems, and even improve cohesion if done in a safe and transparent setting. If they are left unaddressed or if the underlying culture isn’t sound, then they can propagate and lead to factions that harm productivity.

Griping is as much part of the holiday season as jingle bells and jelly donuts. I don’t believe complaining is up now because people were grumpier in 2023. Rather I think people just craved connection more than ever. So join in: Traffic after the time change, Tesla service, (super) late patients, prior auths, perioral dermatitis, post-COVID telogen effluvium.

I feel better.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X (formerly Twitter). Write to him at [email protected].

‘Twas the night before Festivus and all through the house, everyone was griping.

In case you’ve only been watching Friends reruns lately, Festivus is a holiday that originated 25 years ago in the last season of Seinfeld. George’s father created it as an alternative to Christmas hype. In addition to an aluminum pole, the holiday features the annual airing of grievances, when one is encouraged to voice complaints. Aluminum poles haven’t replaced Christmas trees, but the spirit of Festivus is still with us in the widespread airing of grievances in 2023.

Kaiser Permanente

Complaining isn’t just a post-pandemic problem. Hector spends quite a bit of time complaining about Paris in the Iliad. That was a few pandemics ago. And repining is ubiquitous in literature — as human as walking on two limbs it seems. Ostensibly, we complain to effect change: Something is wrong and we expect it to be different. But that’s not the whole story. No one believes the weather will improve or the Patriots will play better because we complain about them. So why do we bother?

Even if nothing changes on the outside, it does seem to alter our internal state, serving a healthy psychological function. Putting to words what is aggravating can have the same benefit of deep breathing. We describe it as “getting something off our chest” because that’s what it feels like. We feel unburdened just by saying it out loud. Complaining is also a way to bond with others. We have a strong instinct to be with people like ourselves and what better way to connect than to find common suffering? Think about the last time you complained: Cranky staff, prior auths, Medicare, disrespectful patients, many of your colleagues will nod in agreement, validating your feelings and making you feel less isolated.

There are also maladaptive reasons for whining. It’s obviously an elementary way to get attention or to remove responsibility. It can also be a political weapon (office politics included). It’s such a potent way to connect that it’s used to build alliances and clout. “Washington is doing a great job,” said no candidate ever. No, if you want to get people on your side, find something irritating and complain to everyone how annoying it is. This solidifies “us” versus “them,” which can harm organizations and families alike.

Yet, eliminating all complaints is neither feasible, nor probably advisable. You could try to make your office a complaint-free zone, but the likely result would be to push any griping to the remote corners where you can no longer hear them. These criticisms might have uncovered missed opportunities, identify problems, and even improve cohesion if done in a safe and transparent setting. If they are left unaddressed or if the underlying culture isn’t sound, then they can propagate and lead to factions that harm productivity.

Griping is as much part of the holiday season as jingle bells and jelly donuts. I don’t believe complaining is up now because people were grumpier in 2023. Rather I think people just craved connection more than ever. So join in: Traffic after the time change, Tesla service, (super) late patients, prior auths, perioral dermatitis, post-COVID telogen effluvium.

I feel better.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X (formerly Twitter). Write to him at [email protected].

‘Twas the night before Festivus and all through the house, everyone was griping.

In case you’ve only been watching Friends reruns lately, Festivus is a holiday that originated 25 years ago in the last season of Seinfeld. George’s father created it as an alternative to Christmas hype. In addition to an aluminum pole, the holiday features the annual airing of grievances, when one is encouraged to voice complaints. Aluminum poles haven’t replaced Christmas trees, but the spirit of Festivus is still with us in the widespread airing of grievances in 2023.

Kaiser Permanente

Complaining isn’t just a post-pandemic problem. Hector spends quite a bit of time complaining about Paris in the Iliad. That was a few pandemics ago. And repining is ubiquitous in literature — as human as walking on two limbs it seems. Ostensibly, we complain to effect change: Something is wrong and we expect it to be different. But that’s not the whole story. No one believes the weather will improve or the Patriots will play better because we complain about them. So why do we bother?

Even if nothing changes on the outside, it does seem to alter our internal state, serving a healthy psychological function. Putting to words what is aggravating can have the same benefit of deep breathing. We describe it as “getting something off our chest” because that’s what it feels like. We feel unburdened just by saying it out loud. Complaining is also a way to bond with others. We have a strong instinct to be with people like ourselves and what better way to connect than to find common suffering? Think about the last time you complained: Cranky staff, prior auths, Medicare, disrespectful patients, many of your colleagues will nod in agreement, validating your feelings and making you feel less isolated.

There are also maladaptive reasons for whining. It’s obviously an elementary way to get attention or to remove responsibility. It can also be a political weapon (office politics included). It’s such a potent way to connect that it’s used to build alliances and clout. “Washington is doing a great job,” said no candidate ever. No, if you want to get people on your side, find something irritating and complain to everyone how annoying it is. This solidifies “us” versus “them,” which can harm organizations and families alike.

Yet, eliminating all complaints is neither feasible, nor probably advisable. You could try to make your office a complaint-free zone, but the likely result would be to push any griping to the remote corners where you can no longer hear them. These criticisms might have uncovered missed opportunities, identify problems, and even improve cohesion if done in a safe and transparent setting. If they are left unaddressed or if the underlying culture isn’t sound, then they can propagate and lead to factions that harm productivity.

Griping is as much part of the holiday season as jingle bells and jelly donuts. I don’t believe complaining is up now because people were grumpier in 2023. Rather I think people just craved connection more than ever. So join in: Traffic after the time change, Tesla service, (super) late patients, prior auths, perioral dermatitis, post-COVID telogen effluvium.

I feel better.

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on X (formerly Twitter). Write to him at [email protected].

For much of his life, 32-year-old Michael Smith had a war going on in his head.

After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again. 

Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.

He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control. 

“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “ 

Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results. 

Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.

But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise. 

But most agree that in the battle against obesity, one crucial organ has been overlooked.

“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”

A Break in the Machine

Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.

“We like to think that we have control over what we eat, but the brain is also integrating all of these factors that we don’t fully understand in ways that shape our decisions,” said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”

Mounting evidence suggests that in people with obesity, something in the machine is broken.

One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack. 

A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.

“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.

Gut-brain pathways that tell us we’re full may also be impaired.

In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).

In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).

In those with obesity, the brain barely responded at all. 

“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”

Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.

“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.

Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.

The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.

“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”

In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.

All this raises a crucial question: How do these circuits and pathways malfunction in the first place?

What Breaks the Brain?

Genes, scientists agree, play a role. 

Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments. 

While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.

Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.

At the population level, “our genes don’t change that much in less than a generation,” she said.

But our food supply has.

Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.

“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias. 

In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food. 

The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.

Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.

“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall. 

Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else. 

Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full. 

“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science. 

Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.

And once these brain changes are made, they are hard to reverse.

“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”

That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.

A New Era of Brain-Based Solutions

In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.

“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.

A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses. 

While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.

His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full. 

The weight began to fall off again.

Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.

“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’” 

A Multi-Pronged Approach

Dr. Halpern, at Penn, has also been hearing success stories.

In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder. 

All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.

The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.

Thus far, all three are seeing promising results.

“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”

Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.

He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.

Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.

“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.

Still, not everyone believes brain-based drugs and surgeries are the answer. 

David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.

He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.

“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.” 

Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.

“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”

Smith says understanding this has been a big part of his success.

He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.

Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.

“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
 

A version of this article appeared on WebMD.com .

For much of his life, 32-year-old Michael Smith had a war going on in his head.

After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again. 

Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.

He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control. 

“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “ 

Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results. 

Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.

But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise. 

But most agree that in the battle against obesity, one crucial organ has been overlooked.

“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”

A Break in the Machine

Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.

“We like to think that we have control over what we eat, but the brain is also integrating all of these factors that we don’t fully understand in ways that shape our decisions,” said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”

Mounting evidence suggests that in people with obesity, something in the machine is broken.

One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack. 

A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.

“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.

Gut-brain pathways that tell us we’re full may also be impaired.

In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).

In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).

In those with obesity, the brain barely responded at all. 

“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”

Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.

“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.

Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.

The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.

“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”

In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.

All this raises a crucial question: How do these circuits and pathways malfunction in the first place?

What Breaks the Brain?

Genes, scientists agree, play a role. 

Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments. 

While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.

Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.

At the population level, “our genes don’t change that much in less than a generation,” she said.

But our food supply has.

Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.

“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias. 

In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food. 

The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.

Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.

“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall. 

Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else. 

Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full. 

“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science. 

Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.

And once these brain changes are made, they are hard to reverse.

“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”

That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.

A New Era of Brain-Based Solutions

In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.

“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.

A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses. 

While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.

His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full. 

The weight began to fall off again.

Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.

“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’” 

A Multi-Pronged Approach

Dr. Halpern, at Penn, has also been hearing success stories.

In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder. 

All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.

The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.

Thus far, all three are seeing promising results.

“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”

Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.

He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.

Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.

“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.

Still, not everyone believes brain-based drugs and surgeries are the answer. 

David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.

He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.

“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.” 

Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.

“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”

Smith says understanding this has been a big part of his success.

He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.

Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.

“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
 

A version of this article appeared on WebMD.com .

For much of his life, 32-year-old Michael Smith had a war going on in his head.

After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again. 

Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.

He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control. 

“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “ 

Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results. 

Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.

But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise. 

But most agree that in the battle against obesity, one crucial organ has been overlooked.

“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”

A Break in the Machine

Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.

“We like to think that we have control over what we eat, but the brain is also integrating all of these factors that we don’t fully understand in ways that shape our decisions,” said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”

Mounting evidence suggests that in people with obesity, something in the machine is broken.

One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack. 

A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.

“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.

Gut-brain pathways that tell us we’re full may also be impaired.

In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).

In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).

In those with obesity, the brain barely responded at all. 

“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”

Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.

“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.

Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.

The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.

“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”

In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.

All this raises a crucial question: How do these circuits and pathways malfunction in the first place?

What Breaks the Brain?

Genes, scientists agree, play a role. 

Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments. 

While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.

Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.

At the population level, “our genes don’t change that much in less than a generation,” she said.

But our food supply has.

Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.

“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias. 

In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food. 

The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.

Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.

“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall. 

Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else. 

Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full. 

“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science. 

Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.

And once these brain changes are made, they are hard to reverse.

“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”

That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.

A New Era of Brain-Based Solutions

In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.

“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.

A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses. 

While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.

His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full. 

The weight began to fall off again.

Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.

“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’” 

A Multi-Pronged Approach

Dr. Halpern, at Penn, has also been hearing success stories.

In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder. 

All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.

The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.

Thus far, all three are seeing promising results.

“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”

Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.

He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.

Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.

“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.

Still, not everyone believes brain-based drugs and surgeries are the answer. 

David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.

He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.

“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.” 

Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.

“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”

Smith says understanding this has been a big part of his success.

He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.

Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.

“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
 

A version of this article appeared on WebMD.com .