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mRNA Cancer Vaccines: Pipeline Insights for Clinicians
Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.
In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.
Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.
Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.
“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”
Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”
Challenges With mRNA Vaccines
Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.
Global Research Status
According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.
Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.
Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.
Leading Studies
Lepique highlighted the most advanced studies to date:
- Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
- Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
- Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.
Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.
Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.
Advantages of mRNA Technology
Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.
“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.
It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.
Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.
Outlook and Limitations
Lima noted that although the projected efficacy is promising, definitive results are still pending.
“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.
According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.
“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.
Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.
Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”
This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.
Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.
In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.
Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.
Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.
“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”
Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”
Challenges With mRNA Vaccines
Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.
Global Research Status
According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.
Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.
Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.
Leading Studies
Lepique highlighted the most advanced studies to date:
- Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
- Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
- Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.
Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.
Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.
Advantages of mRNA Technology
Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.
“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.
It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.
Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.
Outlook and Limitations
Lima noted that although the projected efficacy is promising, definitive results are still pending.
“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.
According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.
“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.
Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.
Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”
This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.
Since 1965, messenger RNA (mRNA) vaccines have been studied for cancer treatment, but it was the technological advances in vaccines during the COVID pandemic that helped accelerate research. Currently, no vaccine has been approved for tumor treatment, although many clinical studies are ongoing worldwide. According to experts consulted by Medscape’s Portuguese edition, the outlook is very promising, and these studies are expected to open doors for personalized therapies.
In cancer treatment, the vaccine would function as an immunotherapy, in which the immune system can be “trained” to act against an invader. Just as with pathogens, the platform would use parts of the tumor — which have altered proteins or are expressed at abnormal levels — to teach the body to defend itself against cancer.
Vladmir Lima, MD, PhD, clinical oncologist at A.C. Camargo Cancer Center, São Paulo, Brazil, explained that with this technology it will be possible to produce personalized vaccines, which prevents, for example, large-scale manufacturing. “In theory, these vaccines can be developed for any tumor type, but this does not mean that efficacy will be the same for all,” he said. Because cancer has specific characteristics in each individual, it is difficult to envision a single vaccine that works for all cancers.
Current evidence suggests the vaccine could be administered after chemotherapy or radiotherapy, with the goal of reducing tumor mass and increasing the effectiveness of mRNA-based treatment, according to Ana Paula Lepique, professor and researcher in tumor immunology at the Institute of Biomedical Sciences, University of São Paulo, São Paulo.
“There is also a study with pancreatic cancer patients, in which the vaccine was administered after surgery,” she explained. “It would not work, for example, to give chemotherapy or radiotherapy while the immune response is being triggered by the vaccine. This would make the vaccine ineffective, since chemotherapy and radiotherapy are toxic to lymphocytes.”
Lepique also clarified that it is possible to combine the vaccine with immunotherapy targeting immune regulatory molecules. “In this case, in addition to administering the mRNA with the antigen, a strategy is used to improve the patient’s immune response.”
Challenges With mRNA Vaccines
Despite being a promising technology, there are challenges, warned Lepique. mRNA molecules degrade quickly when injected into the body, which can compromise vaccine efficacy. To overcome this, researchers have developed nanoencapsulation technologies that protect the molecules and allow safe use in vaccines. “Another alternative is transferring the mRNA into dendritic cells, known as antigen-presenting cells, and then administering these cells to the patient,” she explained.
Global Research Status
According to a study published this year in Med, over 120 clinical trials are exploring mRNA vaccines to treat lung, breast, prostate, and pancreatic tumors, as well as melanoma.
Lepique noted that the countries leading this research are the US, UK, Germany, China, and Japan. “Unfortunately, the US government recently cut funding for mRNA vaccine development and testing, which will likely have significant consequences,” she said.
Lepique reported that Brazilian researchers are collaborating with international institutions to develop these vaccines. “The Brazilian government, through the Ministry of Health and the Ministry of Science, Technology, and Innovation, recently announced investments in mRNA technologies for vaccines. While not specifically targeting cancer, these investments could also benefit this field,” she clarified.
Leading Studies
Lepique highlighted the most advanced studies to date:
- Pancreatic cancer: A study published in Nature in February demonstrated that a personalized mRNA vaccine reduced the risk for recurrence after surgery in 16 patients, with 3 years of follow-up.
- Melanoma: A study published in The Lancet reported improved survival in melanoma patients after mRNA vaccine administration combined with the checkpoint inhibitor pembrolizumab applied after surgical tumor resection.
- Universal vaccine: A study in Nature Biomedical Engineering described the creation of a “generic” vaccine capable of activating the patient’s immune system and inducing tumor regression. Lepique explained that this vaccine acts more as an immune response modulator than a classical neoantigen-specific vaccine. “Because it is not limited to a single neoantigen, it could potentially be universal, though further testing is needed to determine efficacy across all cancer types,” she added.
Lima highlighted a 2024 study being conducted by MSD and Moderna against lung cancer, with results yet to be published. “Patients first receive immunotherapy after surgery. Once the vaccine is ready, it is added to the ongoing immunotherapy,” he explained. The global phase 3 study involves 868 patients with resected lung cancer who previously underwent chemotherapy. Participants receive the vaccine (1 mg every 3 weeks, up to nine doses) alongside pembrolizumab (400 mg every 6 weeks, up to nine cycles) over approximately 1 year.
Other mRNA vaccines remain in early-stage development. For example, in May 2024, the UK National Health Service recruited participants for a personalized colorectal cancer mRNA vaccine trial.
Advantages of mRNA Technology
Experts noted that mRNA-based cancer vaccines are considered safer for patients because the tumor mRNA is synthesized in the laboratory. According to Lepique, these vaccines are more specific than many other cancer therapies, and therefore carry a lower risk for serious side effects.
“Clinical studies have shown that these vaccines can generate immunological memory, meaning lymphocytes that recognize tumor antigens remain in the body and can respond to recurrence,” she explained.
It is also possible to combine multiple mRNA molecules in a single vaccine, creating a platform that targets several tumor antigens simultaneously. “Formulations can additionally include adjuvants to further enhance immune responses against tumors,” she said. However, as a personalized therapy, costs are high, and vaccine formulation requires considerable time.
Lima emphasized the customization advantage: “We can take a portion of the patient’s tumor, sequence it to identify alterations, and develop a vaccine specifically for that tumor.” He also highlighted safety data, noting that the platform has been widely used in SARS-CoV-2 vaccine development, providing confidence in large-scale application. “The potential exists to achieve more personalized, tumor-directed immunotherapy with greater scalability,” he explained.
Outlook and Limitations
Lima noted that although the projected efficacy is promising, definitive results are still pending.
“We have very positive expectations, but we must wait for study outcomes. Efficacy may vary across scenarios and among patients. The immune system may also respond against the vaccine itself, potentially reducing effectiveness at times,” he explained.
According to Lima, mRNA vaccines are expected to complement current treatments, enhancing outcomes without replacing conventional approaches entirely.
“It will not be a panacea. These vaccines are likely to add to and improve strategies we already use, but they will not work for all patients in every scenario,” he concluded.
Lepique highlighted the promise of combination strategies. “The outlook is positive, particularly because multiple mRNA types can be combined in a single formulation and used alongside drugs that enhance immune responses,” she explained.
Although mRNA vaccine research has been ongoing for many years, prior results have brought both progress and setbacks. “This new protocol appears more effective [and] capable of generating immunological memory and is also safe,” she noted. Still, she cautioned that cancer presents unique challenges: “The disease has multiple mechanisms to evade immune responses. Additionally, some tumors are naturally unrecognized by the immune system, the so-called ‘cold tumors.’”
This story was translated from Medscape’s Portuguese edition. A version of this article appeared on Medscape.com.
US Health Official Calls for Separating Measles Combination Shots, Pulls Broad COVID Vaccine Support
(Reuters) -A top U.S. health official on Monday called for the combined measles-mumps-rubella shot to be broken up, drawing a quick rebuke from vaccine maker Merck, which said there is no scientific evidence that shows any benefit to doing so.
The U.S. CDC earlier on Monday pulled broad support for COVID-19 shots, saying they should be administered through shared decision-making with a health care provider in accordance with recommendations from Health Secretary Robert F. Kennedy Jr.’s hand-picked vaccine advisory panel.
The acting director of the Centers for Disease Control and Prevention, Jim O’Neill, in an X post on Monday called on vaccine manufacturers to develop three separate vaccines to replace the combined MMR inoculation.
In a September 23 news conference at the White House, President Donald Trump delivered medical advice to pregnant women and parents of young children, repeatedly telling them common vaccines should not be taken together or so early in a child’s life, and urging them not to use or administer Tylenol, against the advice of medical societies.
Kennedy, a long-time anti-vaccine crusader before taking on the nation’s top health post, has linked vaccines to autism and sought to rewrite the country’s immunization policies. He fired all members of the national vaccine advisory board of outside experts and replaced them with new members, many of whom shared his views. The committee is reviewing the childhood vaccine schedule.
The causes of autism are unclear. But no rigorous studies have found links between autism and vaccines or medications, or their components such as thimerosal or formaldehyde. Vaccination rates have declined as autism rates have climbed.
MERCK, EXPERTS DEFEND MMR SHOT
Merck said there is no published scientific evidence that shows any benefit in separating the MMR shot.
According to the U.S. Food and Drug Administration’s website, there are currently no separate single virus shots for measles, mumps or rubella licensed for use in the United States. That means manufacturers could need to go through the FDA approval process before any become available.
“Use of the individual components of combination vaccines increases the number of injections for the individual and may result in delayed or missed immunizations,” Merck said in a statement.
Dr. Rana Alissa, president of the Florida chapter of the American Academy of Pediatrics, said the purpose of combining the three shots in the MMR vaccine is not only to save parents extra visits to the doctor’s office.
“Studies have shown that when you give them together, the immune response is much better,” she said. “This is how you get lifelong immunity.”
GSK, which also makes an MMR shot, declined to comment. A spokesman for the U.S. Department of Health and Human Services, where O’Neill is deputy secretary, was not immediately available for comment.
The break-up of the MMR shot would “falsely imply that there is something unsafe about giving the measles, mumps, and rubella vaccines at the same time,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security.
“It would be another example of the federal government pandering to the anti-vaccine movement,” Adalja added.
Earlier in the day, the CDC signed off on the advisers’ recommendations against use of the combined measles-mumps-rubella-varicella vaccine before the age of 4 years because of a slight risk of seizures related to high fevers. Instead, varicella, commonly known as chickenpox, is recommended as a standalone shot.
Merck also makes the measles-mumps-rubella-varicella shot.
CDC CHANGES COVID VIEWS
The new CDC recommendation on the COVID vaccine calls for physician involvement but maintains access for the shot through health insurance.
The immunization schedules will be updated on the CDC website by Tuesday, the agency said.
The recommendations come after upheaval at the CDC, including the ouster of its former Director Susan Monarez, who had resisted changes to vaccine policy advanced by Kennedy. Monarez said she was told to rubber-stamp the committee’s recommendations without reviewing the scientific evidence.
The new advisory panel made its recommendations at a two-day meeting in September that highlighted deep divisions over the future of the U.S. immunization schedules under Kennedy.
The American Academy of Pediatrics, an influential U.S. medical group, has already broken from federal policy and pushed its own vaccine recommendations, suggesting all young children get vaccinated against COVID-19.
The U.S. Food and Drug Administration in August cleared updated COVID-19 vaccines for everyone over age 65, but limited its approval for younger people to those with health risks.
The 3 approved COVID shots are made by Pfizer with German partner BioNTech, Moderna, and Novavax with Sanofi.
(Reporting by Mariam Sunny in Bengaluru, Michael Erman in New York and Julie Steenhuysen in Chicago; Editing by Caroline Humer and Bill Berkrot)■
A version of this article appeared on Medscape.com.
(Reuters) -A top U.S. health official on Monday called for the combined measles-mumps-rubella shot to be broken up, drawing a quick rebuke from vaccine maker Merck, which said there is no scientific evidence that shows any benefit to doing so.
The U.S. CDC earlier on Monday pulled broad support for COVID-19 shots, saying they should be administered through shared decision-making with a health care provider in accordance with recommendations from Health Secretary Robert F. Kennedy Jr.’s hand-picked vaccine advisory panel.
The acting director of the Centers for Disease Control and Prevention, Jim O’Neill, in an X post on Monday called on vaccine manufacturers to develop three separate vaccines to replace the combined MMR inoculation.
In a September 23 news conference at the White House, President Donald Trump delivered medical advice to pregnant women and parents of young children, repeatedly telling them common vaccines should not be taken together or so early in a child’s life, and urging them not to use or administer Tylenol, against the advice of medical societies.
Kennedy, a long-time anti-vaccine crusader before taking on the nation’s top health post, has linked vaccines to autism and sought to rewrite the country’s immunization policies. He fired all members of the national vaccine advisory board of outside experts and replaced them with new members, many of whom shared his views. The committee is reviewing the childhood vaccine schedule.
The causes of autism are unclear. But no rigorous studies have found links between autism and vaccines or medications, or their components such as thimerosal or formaldehyde. Vaccination rates have declined as autism rates have climbed.
MERCK, EXPERTS DEFEND MMR SHOT
Merck said there is no published scientific evidence that shows any benefit in separating the MMR shot.
According to the U.S. Food and Drug Administration’s website, there are currently no separate single virus shots for measles, mumps or rubella licensed for use in the United States. That means manufacturers could need to go through the FDA approval process before any become available.
“Use of the individual components of combination vaccines increases the number of injections for the individual and may result in delayed or missed immunizations,” Merck said in a statement.
Dr. Rana Alissa, president of the Florida chapter of the American Academy of Pediatrics, said the purpose of combining the three shots in the MMR vaccine is not only to save parents extra visits to the doctor’s office.
“Studies have shown that when you give them together, the immune response is much better,” she said. “This is how you get lifelong immunity.”
GSK, which also makes an MMR shot, declined to comment. A spokesman for the U.S. Department of Health and Human Services, where O’Neill is deputy secretary, was not immediately available for comment.
The break-up of the MMR shot would “falsely imply that there is something unsafe about giving the measles, mumps, and rubella vaccines at the same time,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security.
“It would be another example of the federal government pandering to the anti-vaccine movement,” Adalja added.
Earlier in the day, the CDC signed off on the advisers’ recommendations against use of the combined measles-mumps-rubella-varicella vaccine before the age of 4 years because of a slight risk of seizures related to high fevers. Instead, varicella, commonly known as chickenpox, is recommended as a standalone shot.
Merck also makes the measles-mumps-rubella-varicella shot.
CDC CHANGES COVID VIEWS
The new CDC recommendation on the COVID vaccine calls for physician involvement but maintains access for the shot through health insurance.
The immunization schedules will be updated on the CDC website by Tuesday, the agency said.
The recommendations come after upheaval at the CDC, including the ouster of its former Director Susan Monarez, who had resisted changes to vaccine policy advanced by Kennedy. Monarez said she was told to rubber-stamp the committee’s recommendations without reviewing the scientific evidence.
The new advisory panel made its recommendations at a two-day meeting in September that highlighted deep divisions over the future of the U.S. immunization schedules under Kennedy.
The American Academy of Pediatrics, an influential U.S. medical group, has already broken from federal policy and pushed its own vaccine recommendations, suggesting all young children get vaccinated against COVID-19.
The U.S. Food and Drug Administration in August cleared updated COVID-19 vaccines for everyone over age 65, but limited its approval for younger people to those with health risks.
The 3 approved COVID shots are made by Pfizer with German partner BioNTech, Moderna, and Novavax with Sanofi.
(Reporting by Mariam Sunny in Bengaluru, Michael Erman in New York and Julie Steenhuysen in Chicago; Editing by Caroline Humer and Bill Berkrot)■
A version of this article appeared on Medscape.com.
(Reuters) -A top U.S. health official on Monday called for the combined measles-mumps-rubella shot to be broken up, drawing a quick rebuke from vaccine maker Merck, which said there is no scientific evidence that shows any benefit to doing so.
The U.S. CDC earlier on Monday pulled broad support for COVID-19 shots, saying they should be administered through shared decision-making with a health care provider in accordance with recommendations from Health Secretary Robert F. Kennedy Jr.’s hand-picked vaccine advisory panel.
The acting director of the Centers for Disease Control and Prevention, Jim O’Neill, in an X post on Monday called on vaccine manufacturers to develop three separate vaccines to replace the combined MMR inoculation.
In a September 23 news conference at the White House, President Donald Trump delivered medical advice to pregnant women and parents of young children, repeatedly telling them common vaccines should not be taken together or so early in a child’s life, and urging them not to use or administer Tylenol, against the advice of medical societies.
Kennedy, a long-time anti-vaccine crusader before taking on the nation’s top health post, has linked vaccines to autism and sought to rewrite the country’s immunization policies. He fired all members of the national vaccine advisory board of outside experts and replaced them with new members, many of whom shared his views. The committee is reviewing the childhood vaccine schedule.
The causes of autism are unclear. But no rigorous studies have found links between autism and vaccines or medications, or their components such as thimerosal or formaldehyde. Vaccination rates have declined as autism rates have climbed.
MERCK, EXPERTS DEFEND MMR SHOT
Merck said there is no published scientific evidence that shows any benefit in separating the MMR shot.
According to the U.S. Food and Drug Administration’s website, there are currently no separate single virus shots for measles, mumps or rubella licensed for use in the United States. That means manufacturers could need to go through the FDA approval process before any become available.
“Use of the individual components of combination vaccines increases the number of injections for the individual and may result in delayed or missed immunizations,” Merck said in a statement.
Dr. Rana Alissa, president of the Florida chapter of the American Academy of Pediatrics, said the purpose of combining the three shots in the MMR vaccine is not only to save parents extra visits to the doctor’s office.
“Studies have shown that when you give them together, the immune response is much better,” she said. “This is how you get lifelong immunity.”
GSK, which also makes an MMR shot, declined to comment. A spokesman for the U.S. Department of Health and Human Services, where O’Neill is deputy secretary, was not immediately available for comment.
The break-up of the MMR shot would “falsely imply that there is something unsafe about giving the measles, mumps, and rubella vaccines at the same time,” said Dr. Amesh Adalja, an infectious disease expert at the Johns Hopkins Center for Health Security.
“It would be another example of the federal government pandering to the anti-vaccine movement,” Adalja added.
Earlier in the day, the CDC signed off on the advisers’ recommendations against use of the combined measles-mumps-rubella-varicella vaccine before the age of 4 years because of a slight risk of seizures related to high fevers. Instead, varicella, commonly known as chickenpox, is recommended as a standalone shot.
Merck also makes the measles-mumps-rubella-varicella shot.
CDC CHANGES COVID VIEWS
The new CDC recommendation on the COVID vaccine calls for physician involvement but maintains access for the shot through health insurance.
The immunization schedules will be updated on the CDC website by Tuesday, the agency said.
The recommendations come after upheaval at the CDC, including the ouster of its former Director Susan Monarez, who had resisted changes to vaccine policy advanced by Kennedy. Monarez said she was told to rubber-stamp the committee’s recommendations without reviewing the scientific evidence.
The new advisory panel made its recommendations at a two-day meeting in September that highlighted deep divisions over the future of the U.S. immunization schedules under Kennedy.
The American Academy of Pediatrics, an influential U.S. medical group, has already broken from federal policy and pushed its own vaccine recommendations, suggesting all young children get vaccinated against COVID-19.
The U.S. Food and Drug Administration in August cleared updated COVID-19 vaccines for everyone over age 65, but limited its approval for younger people to those with health risks.
The 3 approved COVID shots are made by Pfizer with German partner BioNTech, Moderna, and Novavax with Sanofi.
(Reporting by Mariam Sunny in Bengaluru, Michael Erman in New York and Julie Steenhuysen in Chicago; Editing by Caroline Humer and Bill Berkrot)■
A version of this article appeared on Medscape.com.
Hepatitis D Virus Classified as Carcinogenic: Implications
The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).
Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.
About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.
Virus Biology
HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.
HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.
Cancer Risk
HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.
The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.
Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.
Treatment Options
Randomized controlled trials have demonstrated antiviral efficacy for:
- Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
- Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.
Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.
Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.
Guideline Updates
The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.
IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.
HBV Vaccination
HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.
Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.
Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.
Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.
STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.
Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.
This story was translated from Univadis Germany.
A version of this article appeared on Medscape.com.
The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).
Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.
About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.
Virus Biology
HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.
HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.
Cancer Risk
HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.
The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.
Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.
Treatment Options
Randomized controlled trials have demonstrated antiviral efficacy for:
- Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
- Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.
Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.
Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.
Guideline Updates
The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.
IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.
HBV Vaccination
HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.
Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.
Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.
Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.
STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.
Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.
This story was translated from Univadis Germany.
A version of this article appeared on Medscape.com.
The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).
Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.
About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.
Virus Biology
HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.
HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.
Cancer Risk
HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.
The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.
Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.
Treatment Options
Randomized controlled trials have demonstrated antiviral efficacy for:
- Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
- Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.
Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.
Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.
Guideline Updates
The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.
IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.
HBV Vaccination
HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.
Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.
Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.
Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.
STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.
Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.
This story was translated from Univadis Germany.
A version of this article appeared on Medscape.com.
Physician Compensation: Gains Small, Gaps Large
Few would deny that physicians today face many challenges: a growing and aging patient population, personnel shortages, mounting paperwork, regulatory and reimbursement pressures, and personal burnout. Collectively these could work to worsen patient access to care. Yet despite these headwinds, Doximity’s survey-based Physician Compensation Report 2025 found that more than three-quarters of physicians polled would still choose to enter their profession.
“Physician burnout isn’t new. It’s been a persistent problem over the past decade,” said Amit Phull, MD, chief clinical experience officer at Doximity. “In a Doximity poll of nearly 2,000 physicians conducted in May 2025, 85% reported they feel overworked, up from 73% just four years ago. As a result, about 68% of physicians said they are looking for an employment change or considering early retirement.”
Greater awareness of contemporary trends may help physicians make more-informed career decisions and more effectively advocate for both themselves and the patients who need them, the report’s authors stated.
Compensation Lag May Impact Care
A small overall average compensation increase of 3.7% from 2023 to 2024 – a slightly lower increase than the 5.9% in the prior year – has done little to close existing pay gaps across the profession.
In 2024, average compensation for men rose 5.7% over 2023, compared with just 1.7% for women – widening the gender pay gap to 26% vs 23% in 2023 and matching the gender gap seen in 2022. And significant disparities persist between physicians caring for adults vs children. In some specialties, the pay gap between pediatric and adult specialists exceeded 80% despite practitioners’ similar levels of training and clinical complexity.
Nearly 60% of respondents said reimbursement pressures could affect their ability to serve Medicare or Medicaid patients in the next year. Additionally, 81% reported that reimbursement policies have significantly contributed to the decline of private practices, and more than a third said they could stifle practice growth with compensation concerns forcing them to delay or cancel hiring or expansion plans. Almost 90% reported an adverse impact from physician shortages, with more citing an inability or limited ability to accept new patients.
Narrowing the Gap for Primary Care?
Over the past three years, the percent pay gap between primary care and specialist medicine declined modestly, the report noted. In 2024, surgical specialists earned 87% more than primary care physicians, down from 100% in 2022. Non-surgical specialists, emergency medicine physicians, and Ob/Gyns also continued to earn significantly more than primary care physicians, though the gaps have narrowed slightly.
“These trends come at a time when primary care remains critical to meeting high patient demand, especially amid ongoing physician shortages,” the report stated. “Primary care physicians continue to earn considerably less than many of their medical colleagues despite their essential role in the healthcare system.”
Significantly, many physicians believe that current reimbursement policies have contributed to the steady decline of independent practices in their fields. According to the American Medical Association, the share of physicians working in private practices dropped by 18 percentage points from 60.1% to 42.2% from 2012 to 2024.
The Specialties
This year’s review found that among 20 specialties, the highest average compensation occurred in surgical and procedural specialties, while the lowest paid were, as mentioned, pediatric medicine and primary care. Pediatric nephrology saw the largest average compensation growth in 2024 at 15.6%, yet compensation still lagged behind adult nephrology with a 40% pay gap.
By medical discipline, gastroenterologists ranked 13th overall in average annual compensation. Gastroenterology remained in the top 20 compensated specialties, with average annual compensation of $537,870 – an increase from $514,208 in 2024, representing a 4.5% growth rate over 2023. Neurosurgeons topped the list at $749,140, followed by thoracic surgeons at $689,969 and orthopedic surgeons at $679,517.
The three lowest-paid branches were all pediatric: endocrinology at $230,426, rheumatology at $231,574, and infectious diseases at $248,322. Pediatric gastroenterology paid somewhat higher at $298,457.
The largest disparities were seen in hematology and oncology, where adult specialists earned 93% more than their pediatric peers. Pediatric gastroenterology showed an 80% pay gap. There were also substantial pay differences across cardiology, pulmonology, and rheumatology. “These gaps appear to reflect a systemic lag in pay for pediatric specialty care, even as demand for pediatric subspecialists continues to rise,” the report stated.
Practice Setting and Location
Where a doctor practices impacts the bottom line, too: in 2024 the highest compensation reported for a metro area was in Rochester, Minnesota (the Mayo Clinic effect?), at $495,532, while the lowest reported was in Durham-Chapel Hill, North Carolina, at $368,782. St. Louis, Missouri ($484,883) and Los Angeles, California ($470,198) were 2nd and 3rd at the top of the list. Rochester, Minnesota, also emerged as best for annual compensation after cost-of-living adjustment, while Boston, Massachusetts, occupied the bottom rung.
The Gender Effect
With a women’s pay increase in 2024 of just 1.7%, the gender gap returned to its 2022-level disparity of 26%, with women physicians earning an average of $120,917 less than men after adjusting for specialty, location, and years of experience.
Doximity’s analysis of data from 2014 to 2019 estimated that on average men make at least $2 million more than women over the course of a 40-year career. This gap is often attributed to the fewer hours worked by female physician with their generally heavier familial responsibilities, “but Doximity’s gender wage gap analysis controls for the number of hours worked and career stage, along with specialty, work type, employment status, region, and credentials,” Phull said.
Women physicians had lower average earnings than men physicians across all specialties, a trend consistent with prior years. As a percentage of pay, the largest gender disparity was seen in pediatric nephrology (16.5%), a specialty that in fact saw the largest annual growth in physician pay. Neurosurgery had the smallest gender gap at 11.3%, while infectious diseases came in at 11.5% and oncology at 12%.
According to Maria T. Abreu, MD, AGAF, executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai Medical Center in Los Angeles and past president of AGA, the remuneration gender gap in gastroenterology is being taken seriously by AGA and several other GI societies. “The discrepancies in pay start from the beginning and therefore are magnified over time. We are helping to empower women to negotiate better as well as to gather data on the roots of inequity, she told GI & Hepatology News.
The AGA Women’s Committee has developed a project to support the advancement of women in gastroenterology, Abreu said. The initiative, which includes the AGA Gender Equity Framework and Gender Equity Road Map. focuses attention on disparities in the workplace and promotes opportunities for women’s leadership, career advancement, mentorship and physician health and wellness, she added.
Are these disparities due mainly to the “motherhood penalty,” with career interruption and time lost to maternity leave and fewer hours worked owing to the greater parenting burden of physician mothers? Or are they due to the systemic effects of gender expectations around compensation?
Hours worked appear to be a factor. A 2017 study of dual physician couples found that among childless respondents men worked an average of 57 hours and women 52 hours weekly. Compared with childless men, men with children worked similar numbers of hours weekly. However, compared with childless physicians, mothers worked significantly fewer hours – roughly 40 to 43 hours weekly – depending on the age of their youngest child.
Abreu pushed back on this stereotype. “Most women physicians, including gastroenterologists, do not take the maternity leave they are allowed because they are concerned about burdening their colleagues,” she said. “Thus, it is unlikely to explain the disparities. Many systemic issues remain challenging, but we want women to be empowered to advocate for themselves at the time of hiring and along the arc of their career paths.”
In Abreu’s view, having women assume more leadership roles in the field of gastroenterology provides an opportunity to focus on reducing the disparities in compensation.
Regardless of gender, among all physicians surveyed, autonomy and work-life balance appeared to be a high priority: 77% of doctors said they would be willing to accept or have already accepted lower pay for more autonomy or work-life balance. “Overwork appears to be especially prevalent among women physicians,” said Phull, noting that 91% of women respondents reported being overworked compared with 80% of men. “This overwork has compelled 74% of women to consider making a career change, compared with 62% of men.” Differences emerged among specialties as well: 90% of primary care physicians said they are overworked compared with 84% of surgeons and 83% of non-surgical specialists.
Looking ahead, the report raised an important question. Are we relying too heavily on physicians rather than addressing the underlying need for policies that support a healthier, more sustainable future for all? “Building that future will take more than physician dedication alone,” Phull said. “It will require meaningful collaboration across the entire health care ecosystem – including health systems, hospitals, payors, and policymakers. And physicians must not only have a voice in shaping the path forward; they must have a seat at the table.”
Abreu reported no conflicts of interest in regard to her comments.
Few would deny that physicians today face many challenges: a growing and aging patient population, personnel shortages, mounting paperwork, regulatory and reimbursement pressures, and personal burnout. Collectively these could work to worsen patient access to care. Yet despite these headwinds, Doximity’s survey-based Physician Compensation Report 2025 found that more than three-quarters of physicians polled would still choose to enter their profession.
“Physician burnout isn’t new. It’s been a persistent problem over the past decade,” said Amit Phull, MD, chief clinical experience officer at Doximity. “In a Doximity poll of nearly 2,000 physicians conducted in May 2025, 85% reported they feel overworked, up from 73% just four years ago. As a result, about 68% of physicians said they are looking for an employment change or considering early retirement.”
Greater awareness of contemporary trends may help physicians make more-informed career decisions and more effectively advocate for both themselves and the patients who need them, the report’s authors stated.
Compensation Lag May Impact Care
A small overall average compensation increase of 3.7% from 2023 to 2024 – a slightly lower increase than the 5.9% in the prior year – has done little to close existing pay gaps across the profession.
In 2024, average compensation for men rose 5.7% over 2023, compared with just 1.7% for women – widening the gender pay gap to 26% vs 23% in 2023 and matching the gender gap seen in 2022. And significant disparities persist between physicians caring for adults vs children. In some specialties, the pay gap between pediatric and adult specialists exceeded 80% despite practitioners’ similar levels of training and clinical complexity.
Nearly 60% of respondents said reimbursement pressures could affect their ability to serve Medicare or Medicaid patients in the next year. Additionally, 81% reported that reimbursement policies have significantly contributed to the decline of private practices, and more than a third said they could stifle practice growth with compensation concerns forcing them to delay or cancel hiring or expansion plans. Almost 90% reported an adverse impact from physician shortages, with more citing an inability or limited ability to accept new patients.
Narrowing the Gap for Primary Care?
Over the past three years, the percent pay gap between primary care and specialist medicine declined modestly, the report noted. In 2024, surgical specialists earned 87% more than primary care physicians, down from 100% in 2022. Non-surgical specialists, emergency medicine physicians, and Ob/Gyns also continued to earn significantly more than primary care physicians, though the gaps have narrowed slightly.
“These trends come at a time when primary care remains critical to meeting high patient demand, especially amid ongoing physician shortages,” the report stated. “Primary care physicians continue to earn considerably less than many of their medical colleagues despite their essential role in the healthcare system.”
Significantly, many physicians believe that current reimbursement policies have contributed to the steady decline of independent practices in their fields. According to the American Medical Association, the share of physicians working in private practices dropped by 18 percentage points from 60.1% to 42.2% from 2012 to 2024.
The Specialties
This year’s review found that among 20 specialties, the highest average compensation occurred in surgical and procedural specialties, while the lowest paid were, as mentioned, pediatric medicine and primary care. Pediatric nephrology saw the largest average compensation growth in 2024 at 15.6%, yet compensation still lagged behind adult nephrology with a 40% pay gap.
By medical discipline, gastroenterologists ranked 13th overall in average annual compensation. Gastroenterology remained in the top 20 compensated specialties, with average annual compensation of $537,870 – an increase from $514,208 in 2024, representing a 4.5% growth rate over 2023. Neurosurgeons topped the list at $749,140, followed by thoracic surgeons at $689,969 and orthopedic surgeons at $679,517.
The three lowest-paid branches were all pediatric: endocrinology at $230,426, rheumatology at $231,574, and infectious diseases at $248,322. Pediatric gastroenterology paid somewhat higher at $298,457.
The largest disparities were seen in hematology and oncology, where adult specialists earned 93% more than their pediatric peers. Pediatric gastroenterology showed an 80% pay gap. There were also substantial pay differences across cardiology, pulmonology, and rheumatology. “These gaps appear to reflect a systemic lag in pay for pediatric specialty care, even as demand for pediatric subspecialists continues to rise,” the report stated.
Practice Setting and Location
Where a doctor practices impacts the bottom line, too: in 2024 the highest compensation reported for a metro area was in Rochester, Minnesota (the Mayo Clinic effect?), at $495,532, while the lowest reported was in Durham-Chapel Hill, North Carolina, at $368,782. St. Louis, Missouri ($484,883) and Los Angeles, California ($470,198) were 2nd and 3rd at the top of the list. Rochester, Minnesota, also emerged as best for annual compensation after cost-of-living adjustment, while Boston, Massachusetts, occupied the bottom rung.
The Gender Effect
With a women’s pay increase in 2024 of just 1.7%, the gender gap returned to its 2022-level disparity of 26%, with women physicians earning an average of $120,917 less than men after adjusting for specialty, location, and years of experience.
Doximity’s analysis of data from 2014 to 2019 estimated that on average men make at least $2 million more than women over the course of a 40-year career. This gap is often attributed to the fewer hours worked by female physician with their generally heavier familial responsibilities, “but Doximity’s gender wage gap analysis controls for the number of hours worked and career stage, along with specialty, work type, employment status, region, and credentials,” Phull said.
Women physicians had lower average earnings than men physicians across all specialties, a trend consistent with prior years. As a percentage of pay, the largest gender disparity was seen in pediatric nephrology (16.5%), a specialty that in fact saw the largest annual growth in physician pay. Neurosurgery had the smallest gender gap at 11.3%, while infectious diseases came in at 11.5% and oncology at 12%.
According to Maria T. Abreu, MD, AGAF, executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai Medical Center in Los Angeles and past president of AGA, the remuneration gender gap in gastroenterology is being taken seriously by AGA and several other GI societies. “The discrepancies in pay start from the beginning and therefore are magnified over time. We are helping to empower women to negotiate better as well as to gather data on the roots of inequity, she told GI & Hepatology News.
The AGA Women’s Committee has developed a project to support the advancement of women in gastroenterology, Abreu said. The initiative, which includes the AGA Gender Equity Framework and Gender Equity Road Map. focuses attention on disparities in the workplace and promotes opportunities for women’s leadership, career advancement, mentorship and physician health and wellness, she added.
Are these disparities due mainly to the “motherhood penalty,” with career interruption and time lost to maternity leave and fewer hours worked owing to the greater parenting burden of physician mothers? Or are they due to the systemic effects of gender expectations around compensation?
Hours worked appear to be a factor. A 2017 study of dual physician couples found that among childless respondents men worked an average of 57 hours and women 52 hours weekly. Compared with childless men, men with children worked similar numbers of hours weekly. However, compared with childless physicians, mothers worked significantly fewer hours – roughly 40 to 43 hours weekly – depending on the age of their youngest child.
Abreu pushed back on this stereotype. “Most women physicians, including gastroenterologists, do not take the maternity leave they are allowed because they are concerned about burdening their colleagues,” she said. “Thus, it is unlikely to explain the disparities. Many systemic issues remain challenging, but we want women to be empowered to advocate for themselves at the time of hiring and along the arc of their career paths.”
In Abreu’s view, having women assume more leadership roles in the field of gastroenterology provides an opportunity to focus on reducing the disparities in compensation.
Regardless of gender, among all physicians surveyed, autonomy and work-life balance appeared to be a high priority: 77% of doctors said they would be willing to accept or have already accepted lower pay for more autonomy or work-life balance. “Overwork appears to be especially prevalent among women physicians,” said Phull, noting that 91% of women respondents reported being overworked compared with 80% of men. “This overwork has compelled 74% of women to consider making a career change, compared with 62% of men.” Differences emerged among specialties as well: 90% of primary care physicians said they are overworked compared with 84% of surgeons and 83% of non-surgical specialists.
Looking ahead, the report raised an important question. Are we relying too heavily on physicians rather than addressing the underlying need for policies that support a healthier, more sustainable future for all? “Building that future will take more than physician dedication alone,” Phull said. “It will require meaningful collaboration across the entire health care ecosystem – including health systems, hospitals, payors, and policymakers. And physicians must not only have a voice in shaping the path forward; they must have a seat at the table.”
Abreu reported no conflicts of interest in regard to her comments.
Few would deny that physicians today face many challenges: a growing and aging patient population, personnel shortages, mounting paperwork, regulatory and reimbursement pressures, and personal burnout. Collectively these could work to worsen patient access to care. Yet despite these headwinds, Doximity’s survey-based Physician Compensation Report 2025 found that more than three-quarters of physicians polled would still choose to enter their profession.
“Physician burnout isn’t new. It’s been a persistent problem over the past decade,” said Amit Phull, MD, chief clinical experience officer at Doximity. “In a Doximity poll of nearly 2,000 physicians conducted in May 2025, 85% reported they feel overworked, up from 73% just four years ago. As a result, about 68% of physicians said they are looking for an employment change or considering early retirement.”
Greater awareness of contemporary trends may help physicians make more-informed career decisions and more effectively advocate for both themselves and the patients who need them, the report’s authors stated.
Compensation Lag May Impact Care
A small overall average compensation increase of 3.7% from 2023 to 2024 – a slightly lower increase than the 5.9% in the prior year – has done little to close existing pay gaps across the profession.
In 2024, average compensation for men rose 5.7% over 2023, compared with just 1.7% for women – widening the gender pay gap to 26% vs 23% in 2023 and matching the gender gap seen in 2022. And significant disparities persist between physicians caring for adults vs children. In some specialties, the pay gap between pediatric and adult specialists exceeded 80% despite practitioners’ similar levels of training and clinical complexity.
Nearly 60% of respondents said reimbursement pressures could affect their ability to serve Medicare or Medicaid patients in the next year. Additionally, 81% reported that reimbursement policies have significantly contributed to the decline of private practices, and more than a third said they could stifle practice growth with compensation concerns forcing them to delay or cancel hiring or expansion plans. Almost 90% reported an adverse impact from physician shortages, with more citing an inability or limited ability to accept new patients.
Narrowing the Gap for Primary Care?
Over the past three years, the percent pay gap between primary care and specialist medicine declined modestly, the report noted. In 2024, surgical specialists earned 87% more than primary care physicians, down from 100% in 2022. Non-surgical specialists, emergency medicine physicians, and Ob/Gyns also continued to earn significantly more than primary care physicians, though the gaps have narrowed slightly.
“These trends come at a time when primary care remains critical to meeting high patient demand, especially amid ongoing physician shortages,” the report stated. “Primary care physicians continue to earn considerably less than many of their medical colleagues despite their essential role in the healthcare system.”
Significantly, many physicians believe that current reimbursement policies have contributed to the steady decline of independent practices in their fields. According to the American Medical Association, the share of physicians working in private practices dropped by 18 percentage points from 60.1% to 42.2% from 2012 to 2024.
The Specialties
This year’s review found that among 20 specialties, the highest average compensation occurred in surgical and procedural specialties, while the lowest paid were, as mentioned, pediatric medicine and primary care. Pediatric nephrology saw the largest average compensation growth in 2024 at 15.6%, yet compensation still lagged behind adult nephrology with a 40% pay gap.
By medical discipline, gastroenterologists ranked 13th overall in average annual compensation. Gastroenterology remained in the top 20 compensated specialties, with average annual compensation of $537,870 – an increase from $514,208 in 2024, representing a 4.5% growth rate over 2023. Neurosurgeons topped the list at $749,140, followed by thoracic surgeons at $689,969 and orthopedic surgeons at $679,517.
The three lowest-paid branches were all pediatric: endocrinology at $230,426, rheumatology at $231,574, and infectious diseases at $248,322. Pediatric gastroenterology paid somewhat higher at $298,457.
The largest disparities were seen in hematology and oncology, where adult specialists earned 93% more than their pediatric peers. Pediatric gastroenterology showed an 80% pay gap. There were also substantial pay differences across cardiology, pulmonology, and rheumatology. “These gaps appear to reflect a systemic lag in pay for pediatric specialty care, even as demand for pediatric subspecialists continues to rise,” the report stated.
Practice Setting and Location
Where a doctor practices impacts the bottom line, too: in 2024 the highest compensation reported for a metro area was in Rochester, Minnesota (the Mayo Clinic effect?), at $495,532, while the lowest reported was in Durham-Chapel Hill, North Carolina, at $368,782. St. Louis, Missouri ($484,883) and Los Angeles, California ($470,198) were 2nd and 3rd at the top of the list. Rochester, Minnesota, also emerged as best for annual compensation after cost-of-living adjustment, while Boston, Massachusetts, occupied the bottom rung.
The Gender Effect
With a women’s pay increase in 2024 of just 1.7%, the gender gap returned to its 2022-level disparity of 26%, with women physicians earning an average of $120,917 less than men after adjusting for specialty, location, and years of experience.
Doximity’s analysis of data from 2014 to 2019 estimated that on average men make at least $2 million more than women over the course of a 40-year career. This gap is often attributed to the fewer hours worked by female physician with their generally heavier familial responsibilities, “but Doximity’s gender wage gap analysis controls for the number of hours worked and career stage, along with specialty, work type, employment status, region, and credentials,” Phull said.
Women physicians had lower average earnings than men physicians across all specialties, a trend consistent with prior years. As a percentage of pay, the largest gender disparity was seen in pediatric nephrology (16.5%), a specialty that in fact saw the largest annual growth in physician pay. Neurosurgery had the smallest gender gap at 11.3%, while infectious diseases came in at 11.5% and oncology at 12%.
According to Maria T. Abreu, MD, AGAF, executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai Medical Center in Los Angeles and past president of AGA, the remuneration gender gap in gastroenterology is being taken seriously by AGA and several other GI societies. “The discrepancies in pay start from the beginning and therefore are magnified over time. We are helping to empower women to negotiate better as well as to gather data on the roots of inequity, she told GI & Hepatology News.
The AGA Women’s Committee has developed a project to support the advancement of women in gastroenterology, Abreu said. The initiative, which includes the AGA Gender Equity Framework and Gender Equity Road Map. focuses attention on disparities in the workplace and promotes opportunities for women’s leadership, career advancement, mentorship and physician health and wellness, she added.
Are these disparities due mainly to the “motherhood penalty,” with career interruption and time lost to maternity leave and fewer hours worked owing to the greater parenting burden of physician mothers? Or are they due to the systemic effects of gender expectations around compensation?
Hours worked appear to be a factor. A 2017 study of dual physician couples found that among childless respondents men worked an average of 57 hours and women 52 hours weekly. Compared with childless men, men with children worked similar numbers of hours weekly. However, compared with childless physicians, mothers worked significantly fewer hours – roughly 40 to 43 hours weekly – depending on the age of their youngest child.
Abreu pushed back on this stereotype. “Most women physicians, including gastroenterologists, do not take the maternity leave they are allowed because they are concerned about burdening their colleagues,” she said. “Thus, it is unlikely to explain the disparities. Many systemic issues remain challenging, but we want women to be empowered to advocate for themselves at the time of hiring and along the arc of their career paths.”
In Abreu’s view, having women assume more leadership roles in the field of gastroenterology provides an opportunity to focus on reducing the disparities in compensation.
Regardless of gender, among all physicians surveyed, autonomy and work-life balance appeared to be a high priority: 77% of doctors said they would be willing to accept or have already accepted lower pay for more autonomy or work-life balance. “Overwork appears to be especially prevalent among women physicians,” said Phull, noting that 91% of women respondents reported being overworked compared with 80% of men. “This overwork has compelled 74% of women to consider making a career change, compared with 62% of men.” Differences emerged among specialties as well: 90% of primary care physicians said they are overworked compared with 84% of surgeons and 83% of non-surgical specialists.
Looking ahead, the report raised an important question. Are we relying too heavily on physicians rather than addressing the underlying need for policies that support a healthier, more sustainable future for all? “Building that future will take more than physician dedication alone,” Phull said. “It will require meaningful collaboration across the entire health care ecosystem – including health systems, hospitals, payors, and policymakers. And physicians must not only have a voice in shaping the path forward; they must have a seat at the table.”
Abreu reported no conflicts of interest in regard to her comments.
Supporting Exceptional Researchers
Did you know that the AGA Research Foundation helped support 74 researchers this past May?
But we can’t do it without you. We depend on the generosity of our supporters to make our vision for the future a reality.
When you donate to AGA Research Foundation, you don’t just give funds – you personally give our beneficiaries grant funding that will lead to new discoveries in GI. Your support goes directly towards funding GI research, helping us address immediate needs while building the foundation for long-term solutions. Plus, you’ll become part of a community full of passionate members like you.
It’s easy to make your mark on our efforts to support investigators. Simply visit our website or learn more ways to give here: [email protected] or contact us at [email protected].
Did you know that the AGA Research Foundation helped support 74 researchers this past May?
But we can’t do it without you. We depend on the generosity of our supporters to make our vision for the future a reality.
When you donate to AGA Research Foundation, you don’t just give funds – you personally give our beneficiaries grant funding that will lead to new discoveries in GI. Your support goes directly towards funding GI research, helping us address immediate needs while building the foundation for long-term solutions. Plus, you’ll become part of a community full of passionate members like you.
It’s easy to make your mark on our efforts to support investigators. Simply visit our website or learn more ways to give here: [email protected] or contact us at [email protected].
Did you know that the AGA Research Foundation helped support 74 researchers this past May?
But we can’t do it without you. We depend on the generosity of our supporters to make our vision for the future a reality.
When you donate to AGA Research Foundation, you don’t just give funds – you personally give our beneficiaries grant funding that will lead to new discoveries in GI. Your support goes directly towards funding GI research, helping us address immediate needs while building the foundation for long-term solutions. Plus, you’ll become part of a community full of passionate members like you.
It’s easy to make your mark on our efforts to support investigators. Simply visit our website or learn more ways to give here: [email protected] or contact us at [email protected].
Racial, Ethnic Discrimination Tied to Psychosis Risk
TOPLINE:
Racial and ethnic discrimination was consistently associated with increased risk for psychosis in studies included in a new umbrella review, with odds nearly doubled for both psychotic symptoms and experiences.
METHODOLOGY:
- Researchers searched 5 databases and then conducted an umbrella review of 7 systematic reviews, 4 of which included meta-analyses, published between 2003 and 2023.
- The systematic reviews included 23 primary studies representing more than 40,000 participants from Europe and the US.
- Investigators assessed the potential association between perceived racial or ethnic discrimination (mostly measured using self-reported questionnaires) and risk for psychosis (measured using established questionnaires).
- They assessed the risk for bias using the 16-item A MeaSurement Tool to Assess systematic Reviews, version 2 (AMSTAR-2) checklist.
TAKEAWAY:
- All reviews that included meta-analyses showed significant associations between perceived ethnic discrimination and psychotic symptoms (adjusted odds ratio [aOR], 1.78; 95% CI, 1.3-2.5) and psychotic experiences (pooled OR, 1.9; 95% CI, 1.4-2.7).
- Perceived racial or ethnic discrimination was also strongly linked to delusional symptoms (OR, 2.5; 95% CI, 1.6-4.0) and hallucinatory symptoms (OR, 1.65; 95% CI, 1.3-2.1).
- The largest of the included studies showed a dose-response relationship between higher levels of lifetime perceived racial or ethnic discrimination and greater likelihood of psychotic experiences.
- More robust associations were found in nonclinical populations compared to clinical ones, but there were significant associations in both.
IN PRACTICE:
“Our review was only looking at the impact of a person directly perceiving racism or interpersonal racial or ethnic discrimination; it may be that systemic racism, which can go unseen but still have profound impacts, could further contribute to mental health disparities,” lead investigator India Francis-Crossley, University College London, London, UK, said in a press release.
SOURCE:
The study was published online in PLOS Mental Health.
LIMITATIONS:
The evidence was primarily based on cross-sectional studies and was limited by high heterogeneity. The reviews included showed low or critically low AMSTAR-2 quality scores, which may have affected the robustness of the findings. More robust evidence was observed for psychotic outcomes in nonclinical populations compared to clinical samples. Additionally, the study potentially exacerbated errors or misreporting in the original reviews and did not include relevant structural factors such as income, education, housing, and poverty.
DISCLOSURES:
The study was funded by the University College London-Windsor Fellowship Research Opportunities scholarship, Wellcome Trust PhD Fellowship in Mental Health Science, Mental Health Mission Early Psychosis Workstream, and UK Research and Innovation funding for the Population Mental Health Consortium. The investigators reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Racial and ethnic discrimination was consistently associated with increased risk for psychosis in studies included in a new umbrella review, with odds nearly doubled for both psychotic symptoms and experiences.
METHODOLOGY:
- Researchers searched 5 databases and then conducted an umbrella review of 7 systematic reviews, 4 of which included meta-analyses, published between 2003 and 2023.
- The systematic reviews included 23 primary studies representing more than 40,000 participants from Europe and the US.
- Investigators assessed the potential association between perceived racial or ethnic discrimination (mostly measured using self-reported questionnaires) and risk for psychosis (measured using established questionnaires).
- They assessed the risk for bias using the 16-item A MeaSurement Tool to Assess systematic Reviews, version 2 (AMSTAR-2) checklist.
TAKEAWAY:
- All reviews that included meta-analyses showed significant associations between perceived ethnic discrimination and psychotic symptoms (adjusted odds ratio [aOR], 1.78; 95% CI, 1.3-2.5) and psychotic experiences (pooled OR, 1.9; 95% CI, 1.4-2.7).
- Perceived racial or ethnic discrimination was also strongly linked to delusional symptoms (OR, 2.5; 95% CI, 1.6-4.0) and hallucinatory symptoms (OR, 1.65; 95% CI, 1.3-2.1).
- The largest of the included studies showed a dose-response relationship between higher levels of lifetime perceived racial or ethnic discrimination and greater likelihood of psychotic experiences.
- More robust associations were found in nonclinical populations compared to clinical ones, but there were significant associations in both.
IN PRACTICE:
“Our review was only looking at the impact of a person directly perceiving racism or interpersonal racial or ethnic discrimination; it may be that systemic racism, which can go unseen but still have profound impacts, could further contribute to mental health disparities,” lead investigator India Francis-Crossley, University College London, London, UK, said in a press release.
SOURCE:
The study was published online in PLOS Mental Health.
LIMITATIONS:
The evidence was primarily based on cross-sectional studies and was limited by high heterogeneity. The reviews included showed low or critically low AMSTAR-2 quality scores, which may have affected the robustness of the findings. More robust evidence was observed for psychotic outcomes in nonclinical populations compared to clinical samples. Additionally, the study potentially exacerbated errors or misreporting in the original reviews and did not include relevant structural factors such as income, education, housing, and poverty.
DISCLOSURES:
The study was funded by the University College London-Windsor Fellowship Research Opportunities scholarship, Wellcome Trust PhD Fellowship in Mental Health Science, Mental Health Mission Early Psychosis Workstream, and UK Research and Innovation funding for the Population Mental Health Consortium. The investigators reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Racial and ethnic discrimination was consistently associated with increased risk for psychosis in studies included in a new umbrella review, with odds nearly doubled for both psychotic symptoms and experiences.
METHODOLOGY:
- Researchers searched 5 databases and then conducted an umbrella review of 7 systematic reviews, 4 of which included meta-analyses, published between 2003 and 2023.
- The systematic reviews included 23 primary studies representing more than 40,000 participants from Europe and the US.
- Investigators assessed the potential association between perceived racial or ethnic discrimination (mostly measured using self-reported questionnaires) and risk for psychosis (measured using established questionnaires).
- They assessed the risk for bias using the 16-item A MeaSurement Tool to Assess systematic Reviews, version 2 (AMSTAR-2) checklist.
TAKEAWAY:
- All reviews that included meta-analyses showed significant associations between perceived ethnic discrimination and psychotic symptoms (adjusted odds ratio [aOR], 1.78; 95% CI, 1.3-2.5) and psychotic experiences (pooled OR, 1.9; 95% CI, 1.4-2.7).
- Perceived racial or ethnic discrimination was also strongly linked to delusional symptoms (OR, 2.5; 95% CI, 1.6-4.0) and hallucinatory symptoms (OR, 1.65; 95% CI, 1.3-2.1).
- The largest of the included studies showed a dose-response relationship between higher levels of lifetime perceived racial or ethnic discrimination and greater likelihood of psychotic experiences.
- More robust associations were found in nonclinical populations compared to clinical ones, but there were significant associations in both.
IN PRACTICE:
“Our review was only looking at the impact of a person directly perceiving racism or interpersonal racial or ethnic discrimination; it may be that systemic racism, which can go unseen but still have profound impacts, could further contribute to mental health disparities,” lead investigator India Francis-Crossley, University College London, London, UK, said in a press release.
SOURCE:
The study was published online in PLOS Mental Health.
LIMITATIONS:
The evidence was primarily based on cross-sectional studies and was limited by high heterogeneity. The reviews included showed low or critically low AMSTAR-2 quality scores, which may have affected the robustness of the findings. More robust evidence was observed for psychotic outcomes in nonclinical populations compared to clinical samples. Additionally, the study potentially exacerbated errors or misreporting in the original reviews and did not include relevant structural factors such as income, education, housing, and poverty.
DISCLOSURES:
The study was funded by the University College London-Windsor Fellowship Research Opportunities scholarship, Wellcome Trust PhD Fellowship in Mental Health Science, Mental Health Mission Early Psychosis Workstream, and UK Research and Innovation funding for the Population Mental Health Consortium. The investigators reported having no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
Mental Health Practitioners Continue to Decrease Despite Aging Vet Population
This article has been updated with a response from the US Department of Veterans Affairs.
The number of US Department of Veterans Affairs (VA) geriatric mental health professionals is failing to keep pace with a growing population of older veterans: nearly 8 million are aged ≥ 65 years. VA psychologists may treat older veterans in primary care settings or community living centers, but many lack formal training in geropsychology.
Some psychologists with the proper training to treat this population are leaving the workforce; a survey by the VA Office of Inspector General found psychology was the most frequently reported severe clinical occupational staffing shortage and the most frequently reported Hybrid Title 38 severe shortage occupation, with 57% of 139 facilities reporting it as a shortage. According to the September Workforce Dashboard, the VA has lost > 200 psychologists in 2025.
Veterans aged ≥ 65 years have higher rates of combined medical and mental health diagnoses than younger veterans and older nonveterans. Nearly 1 of 5 older veterans enrolled in US Department of Veterans Affairs (VA) health care services have confirmed mental health diagnoses, and another 26% have documented mental health concerns without a formal diagnosis in their health record.
Older veterans also tend to have more complex mental health issues than younger adults. Posttraumatic stress nearly doubles their risk of dementia, and their psychiatric diagnoses may be complicated by co-occurring delirium, social isolation/loneliness, and polypharmacy.
According to reporting by The War Horse, the VA has been instituting limits on one-on-one mental health therapy and transitioning veterans to lower levels of treatment after having been told to stop treating them for long, indeterminate periods prior to referring them to group therapy, primary care, or discharging them altogether. In a statement to Federal Practitioner, VA Press Secretary Pete Kasperowicz refuted the reporting from The War Horse.
"The War Horse story is false. VA does not put caps on one-on-one mental health sessions for veterans with clinical care needs," he told Federal Practitioner. "VA works with veterans over an initial eight to 15 mental health sessions, and collaboratively plans any needed follow-on care. As part of this process, veterans and their health care team decide together how to address ongoing needs, including whether to step down to other types of care and self-maintenance, or continue with VA therapy."
The smaller pool of qualified mental health practitioners also may be due to medical students not knowing enough about the category. A study of 136 medical students and 61 internal medicine residents at an academic health center evaluated their beliefs and attitudes regarding 25 content areas essential to the primary care of older adults. Students and residents expressed similar beliefs about the importance of content areas, and attitudes toward aging did not appreciably differ. However, students rated lower in knowledge in areas surrounding general primary care, such as chronic conditions and medications. Residents reported larger gap scores in areas that reflected specialists’ expertise (eg, driving risk, cognition, and psychiatric symptoms).
VA does have channels for filling the gap in geriatric health care. Established in 1975, Geriatric Research, Education, and Clinical Centers (GRECCs), are the department’s centers of excellence focused on aging. Currently, there are 20 GRECCs across the country, each connected with a major research university. Studies focus on aging, for example, examining the effects of Alzheimer’s disease or traumatic brain injuries.
Geriatric Scholars
To specifically fill the gap in mental health care, the Geriatric Scholars Program (GSP) was developed in 2008. Initially focused on primary care physicians, nurse practitioners, physician assistants, and pharmacists, the program later expanded to include other disciplines, including psychiatrists. In 2013, the GSP–Psychology Track (GSP-P) was developed because there were no commercially available training in geropsychology for licensed psychologists. GSP-P is based on an evidence-based educational model for the VA primary care workforce and includes a stepwise curriculum design, pilot implementation, and program evaluation.
A recent survey that assessed the track’s effectiveness found respondents “strongly agreed” that participation in the program improved their geropsychology knowledge and skills. That positive reaction led to shifts in practice that had a positive impact on VA organizational goals. Several GSP-P graduates have become board certified in geropsychology and many proceed to supervise geropsychology-focused clinical rotations for psychology practicum students, predoctoral interns, and postdoctoral fellows.
Whether programs such as GSP-P can adequately address the dwindling number of VA mental health care professionals remains to be seen. More than 160 doctors, psychologists, nurses, and researchers sent a letter to VA Secretary Doug Collins, the VA inspector general, and congressional leaders on Sept. 24 warning that workforce reductions and moves to outsource care will harm veterans.
“We have witnessed these ongoing harms and can provide evidence and testimony of their impacts,” the letter read. By the next day, the number of signees had increased to 350.
Though these shortages may impact their mental health care, older veterans could have an edge in mental resilience. While research in younger adults has found positive linear associations between physical health difficulties and severity of psychiatric symptoms, older veterans may benefit from what researchers have called an “aging paradox,” in which mental health improves later in life despite declining physical and cognitive function. A 2021 study suggests that prevention and treatment strategies designed to foster attachment security, mindfulness, and purpose in life may help enhance psychological resilience to physical health difficulties in older veterans.
This article has been updated with a response from the US Department of Veterans Affairs.
The number of US Department of Veterans Affairs (VA) geriatric mental health professionals is failing to keep pace with a growing population of older veterans: nearly 8 million are aged ≥ 65 years. VA psychologists may treat older veterans in primary care settings or community living centers, but many lack formal training in geropsychology.
Some psychologists with the proper training to treat this population are leaving the workforce; a survey by the VA Office of Inspector General found psychology was the most frequently reported severe clinical occupational staffing shortage and the most frequently reported Hybrid Title 38 severe shortage occupation, with 57% of 139 facilities reporting it as a shortage. According to the September Workforce Dashboard, the VA has lost > 200 psychologists in 2025.
Veterans aged ≥ 65 years have higher rates of combined medical and mental health diagnoses than younger veterans and older nonveterans. Nearly 1 of 5 older veterans enrolled in US Department of Veterans Affairs (VA) health care services have confirmed mental health diagnoses, and another 26% have documented mental health concerns without a formal diagnosis in their health record.
Older veterans also tend to have more complex mental health issues than younger adults. Posttraumatic stress nearly doubles their risk of dementia, and their psychiatric diagnoses may be complicated by co-occurring delirium, social isolation/loneliness, and polypharmacy.
According to reporting by The War Horse, the VA has been instituting limits on one-on-one mental health therapy and transitioning veterans to lower levels of treatment after having been told to stop treating them for long, indeterminate periods prior to referring them to group therapy, primary care, or discharging them altogether. In a statement to Federal Practitioner, VA Press Secretary Pete Kasperowicz refuted the reporting from The War Horse.
"The War Horse story is false. VA does not put caps on one-on-one mental health sessions for veterans with clinical care needs," he told Federal Practitioner. "VA works with veterans over an initial eight to 15 mental health sessions, and collaboratively plans any needed follow-on care. As part of this process, veterans and their health care team decide together how to address ongoing needs, including whether to step down to other types of care and self-maintenance, or continue with VA therapy."
The smaller pool of qualified mental health practitioners also may be due to medical students not knowing enough about the category. A study of 136 medical students and 61 internal medicine residents at an academic health center evaluated their beliefs and attitudes regarding 25 content areas essential to the primary care of older adults. Students and residents expressed similar beliefs about the importance of content areas, and attitudes toward aging did not appreciably differ. However, students rated lower in knowledge in areas surrounding general primary care, such as chronic conditions and medications. Residents reported larger gap scores in areas that reflected specialists’ expertise (eg, driving risk, cognition, and psychiatric symptoms).
VA does have channels for filling the gap in geriatric health care. Established in 1975, Geriatric Research, Education, and Clinical Centers (GRECCs), are the department’s centers of excellence focused on aging. Currently, there are 20 GRECCs across the country, each connected with a major research university. Studies focus on aging, for example, examining the effects of Alzheimer’s disease or traumatic brain injuries.
Geriatric Scholars
To specifically fill the gap in mental health care, the Geriatric Scholars Program (GSP) was developed in 2008. Initially focused on primary care physicians, nurse practitioners, physician assistants, and pharmacists, the program later expanded to include other disciplines, including psychiatrists. In 2013, the GSP–Psychology Track (GSP-P) was developed because there were no commercially available training in geropsychology for licensed psychologists. GSP-P is based on an evidence-based educational model for the VA primary care workforce and includes a stepwise curriculum design, pilot implementation, and program evaluation.
A recent survey that assessed the track’s effectiveness found respondents “strongly agreed” that participation in the program improved their geropsychology knowledge and skills. That positive reaction led to shifts in practice that had a positive impact on VA organizational goals. Several GSP-P graduates have become board certified in geropsychology and many proceed to supervise geropsychology-focused clinical rotations for psychology practicum students, predoctoral interns, and postdoctoral fellows.
Whether programs such as GSP-P can adequately address the dwindling number of VA mental health care professionals remains to be seen. More than 160 doctors, psychologists, nurses, and researchers sent a letter to VA Secretary Doug Collins, the VA inspector general, and congressional leaders on Sept. 24 warning that workforce reductions and moves to outsource care will harm veterans.
“We have witnessed these ongoing harms and can provide evidence and testimony of their impacts,” the letter read. By the next day, the number of signees had increased to 350.
Though these shortages may impact their mental health care, older veterans could have an edge in mental resilience. While research in younger adults has found positive linear associations between physical health difficulties and severity of psychiatric symptoms, older veterans may benefit from what researchers have called an “aging paradox,” in which mental health improves later in life despite declining physical and cognitive function. A 2021 study suggests that prevention and treatment strategies designed to foster attachment security, mindfulness, and purpose in life may help enhance psychological resilience to physical health difficulties in older veterans.
This article has been updated with a response from the US Department of Veterans Affairs.
The number of US Department of Veterans Affairs (VA) geriatric mental health professionals is failing to keep pace with a growing population of older veterans: nearly 8 million are aged ≥ 65 years. VA psychologists may treat older veterans in primary care settings or community living centers, but many lack formal training in geropsychology.
Some psychologists with the proper training to treat this population are leaving the workforce; a survey by the VA Office of Inspector General found psychology was the most frequently reported severe clinical occupational staffing shortage and the most frequently reported Hybrid Title 38 severe shortage occupation, with 57% of 139 facilities reporting it as a shortage. According to the September Workforce Dashboard, the VA has lost > 200 psychologists in 2025.
Veterans aged ≥ 65 years have higher rates of combined medical and mental health diagnoses than younger veterans and older nonveterans. Nearly 1 of 5 older veterans enrolled in US Department of Veterans Affairs (VA) health care services have confirmed mental health diagnoses, and another 26% have documented mental health concerns without a formal diagnosis in their health record.
Older veterans also tend to have more complex mental health issues than younger adults. Posttraumatic stress nearly doubles their risk of dementia, and their psychiatric diagnoses may be complicated by co-occurring delirium, social isolation/loneliness, and polypharmacy.
According to reporting by The War Horse, the VA has been instituting limits on one-on-one mental health therapy and transitioning veterans to lower levels of treatment after having been told to stop treating them for long, indeterminate periods prior to referring them to group therapy, primary care, or discharging them altogether. In a statement to Federal Practitioner, VA Press Secretary Pete Kasperowicz refuted the reporting from The War Horse.
"The War Horse story is false. VA does not put caps on one-on-one mental health sessions for veterans with clinical care needs," he told Federal Practitioner. "VA works with veterans over an initial eight to 15 mental health sessions, and collaboratively plans any needed follow-on care. As part of this process, veterans and their health care team decide together how to address ongoing needs, including whether to step down to other types of care and self-maintenance, or continue with VA therapy."
The smaller pool of qualified mental health practitioners also may be due to medical students not knowing enough about the category. A study of 136 medical students and 61 internal medicine residents at an academic health center evaluated their beliefs and attitudes regarding 25 content areas essential to the primary care of older adults. Students and residents expressed similar beliefs about the importance of content areas, and attitudes toward aging did not appreciably differ. However, students rated lower in knowledge in areas surrounding general primary care, such as chronic conditions and medications. Residents reported larger gap scores in areas that reflected specialists’ expertise (eg, driving risk, cognition, and psychiatric symptoms).
VA does have channels for filling the gap in geriatric health care. Established in 1975, Geriatric Research, Education, and Clinical Centers (GRECCs), are the department’s centers of excellence focused on aging. Currently, there are 20 GRECCs across the country, each connected with a major research university. Studies focus on aging, for example, examining the effects of Alzheimer’s disease or traumatic brain injuries.
Geriatric Scholars
To specifically fill the gap in mental health care, the Geriatric Scholars Program (GSP) was developed in 2008. Initially focused on primary care physicians, nurse practitioners, physician assistants, and pharmacists, the program later expanded to include other disciplines, including psychiatrists. In 2013, the GSP–Psychology Track (GSP-P) was developed because there were no commercially available training in geropsychology for licensed psychologists. GSP-P is based on an evidence-based educational model for the VA primary care workforce and includes a stepwise curriculum design, pilot implementation, and program evaluation.
A recent survey that assessed the track’s effectiveness found respondents “strongly agreed” that participation in the program improved their geropsychology knowledge and skills. That positive reaction led to shifts in practice that had a positive impact on VA organizational goals. Several GSP-P graduates have become board certified in geropsychology and many proceed to supervise geropsychology-focused clinical rotations for psychology practicum students, predoctoral interns, and postdoctoral fellows.
Whether programs such as GSP-P can adequately address the dwindling number of VA mental health care professionals remains to be seen. More than 160 doctors, psychologists, nurses, and researchers sent a letter to VA Secretary Doug Collins, the VA inspector general, and congressional leaders on Sept. 24 warning that workforce reductions and moves to outsource care will harm veterans.
“We have witnessed these ongoing harms and can provide evidence and testimony of their impacts,” the letter read. By the next day, the number of signees had increased to 350.
Though these shortages may impact their mental health care, older veterans could have an edge in mental resilience. While research in younger adults has found positive linear associations between physical health difficulties and severity of psychiatric symptoms, older veterans may benefit from what researchers have called an “aging paradox,” in which mental health improves later in life despite declining physical and cognitive function. A 2021 study suggests that prevention and treatment strategies designed to foster attachment security, mindfulness, and purpose in life may help enhance psychological resilience to physical health difficulties in older veterans.
Parental Mental Disorders May Double Offspring Mortality Risk
TOPLINE:
Offspring of parents with mental disorders had nearly double the risk for mortality, especially from unnatural causes, compared to those with parents did not have a mental disorder, a new Swedish cohort study showed. Additionally, mortality risk was highest when both parents had mental disorders but was not affected by the sex of the affected parent.
METHODOLOGY:
- A nationwide register-based cohort study in Sweden included more than 3.5 million individuals born between 1973 and 2014 (51% men); 35% had a parent with a mental disorder (13% paternal, 16% maternal, and 6% both parents).
- Mental disorder categories included alcohol or substance use, psychotic, mood, anxiety or stress-related, eating, and personality disorders and intellectual disability. Exposure timing was classified by offspring age (mean age, 15.8 years) at parental diagnosis.
- Participants were followed up from birth until death, the death of either parent, emigration (up to 2014), either parent’s emigration, or the end of 2023, whichever came first (median follow-up duration, 20.1 years).
- The main outcome was all-cause mortality; secondary outcomes were deaths from natural and unnatural causes, as well as deaths from cardiovascular disease, cancer, suicide, and unintentional injuries. Cousin comparison analyses were also conducted to account for confounding.
TAKEAWAY:
- During the follow-up, offspring exposed to parental psychiatric disorders had higher overall mortality rates than unexposed offspring (7.9 vs 3.55 per 10,000 person-years). Mortality rates due to natural causes were 4.0 vs 2.4 per 10,000 person-years and were 3.95 vs 1.1 per 10,000 person-years for mortality due to unnatural causes.
- Exposed offspring had an increased risk for mortality due to any cause (adjusted hazard ratio [aHR], 2.1), natural causes (aHR, 1.9), and unnatural causes (aHR, 2.45). Exposure was also associated with an increased risk for cardiovascular and cancer-related death, suicide, and death due to unintentional injuries. The associations remained significant, although slightly attenuated, in cousin comparison analyses.
- The highest risks for mortality were in offspring exposed at ages 1-2 years to both parents having mental disorders (HR for natural causes, 4.5; HR for unnatural causes, 5.3).
- The risk varied by the type of parental mental disorder, with HRs ranging from 1.6 for eating disorders to 2.2 for intellectual disability.
IN PRACTICE:
“Our findings highlight the need for improved surveillance, prevention, and early detection strategies to reduce the risk of premature mortality among offspring exposed to parental mental disorders. Whether additional support for families affected by mental disorders could mitigate the risk warrants further investigation,” the investigators wrote.
SOURCE:
This study was led by Hui Wang, PhD, Karolinska Institutet, Stockholm, Sweden. It was published online in JAMA Psychiatry.
LIMITATIONS:
Reliance on registry data may have led to the misclassification of parental mental disorders. The study lacked data on genetic factors, parenting quality, cohabitation, and social support, and its generalizability may have been limited. Immigration data after 2014 were unavailable, potentially leading to misclassifications of exposure and outcomes. The Patient Register did not distinguish between diagnoses made in general vs psychiatric hospital settings, and cousin comparisons remained susceptible to bias from unmeasured confounding and may have been limited in capturing temporal and familial heterogeneity.
DISCLOSURES:
This study was funded by the Swedish Research Council for Health, Working Life and Welfare and the Heart and Lung Foundation. Wang reported having no relevant financial relationships. The other investigator reported receiving grants from Forte and the Heart and Lung Foundation.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Offspring of parents with mental disorders had nearly double the risk for mortality, especially from unnatural causes, compared to those with parents did not have a mental disorder, a new Swedish cohort study showed. Additionally, mortality risk was highest when both parents had mental disorders but was not affected by the sex of the affected parent.
METHODOLOGY:
- A nationwide register-based cohort study in Sweden included more than 3.5 million individuals born between 1973 and 2014 (51% men); 35% had a parent with a mental disorder (13% paternal, 16% maternal, and 6% both parents).
- Mental disorder categories included alcohol or substance use, psychotic, mood, anxiety or stress-related, eating, and personality disorders and intellectual disability. Exposure timing was classified by offspring age (mean age, 15.8 years) at parental diagnosis.
- Participants were followed up from birth until death, the death of either parent, emigration (up to 2014), either parent’s emigration, or the end of 2023, whichever came first (median follow-up duration, 20.1 years).
- The main outcome was all-cause mortality; secondary outcomes were deaths from natural and unnatural causes, as well as deaths from cardiovascular disease, cancer, suicide, and unintentional injuries. Cousin comparison analyses were also conducted to account for confounding.
TAKEAWAY:
- During the follow-up, offspring exposed to parental psychiatric disorders had higher overall mortality rates than unexposed offspring (7.9 vs 3.55 per 10,000 person-years). Mortality rates due to natural causes were 4.0 vs 2.4 per 10,000 person-years and were 3.95 vs 1.1 per 10,000 person-years for mortality due to unnatural causes.
- Exposed offspring had an increased risk for mortality due to any cause (adjusted hazard ratio [aHR], 2.1), natural causes (aHR, 1.9), and unnatural causes (aHR, 2.45). Exposure was also associated with an increased risk for cardiovascular and cancer-related death, suicide, and death due to unintentional injuries. The associations remained significant, although slightly attenuated, in cousin comparison analyses.
- The highest risks for mortality were in offspring exposed at ages 1-2 years to both parents having mental disorders (HR for natural causes, 4.5; HR for unnatural causes, 5.3).
- The risk varied by the type of parental mental disorder, with HRs ranging from 1.6 for eating disorders to 2.2 for intellectual disability.
IN PRACTICE:
“Our findings highlight the need for improved surveillance, prevention, and early detection strategies to reduce the risk of premature mortality among offspring exposed to parental mental disorders. Whether additional support for families affected by mental disorders could mitigate the risk warrants further investigation,” the investigators wrote.
SOURCE:
This study was led by Hui Wang, PhD, Karolinska Institutet, Stockholm, Sweden. It was published online in JAMA Psychiatry.
LIMITATIONS:
Reliance on registry data may have led to the misclassification of parental mental disorders. The study lacked data on genetic factors, parenting quality, cohabitation, and social support, and its generalizability may have been limited. Immigration data after 2014 were unavailable, potentially leading to misclassifications of exposure and outcomes. The Patient Register did not distinguish between diagnoses made in general vs psychiatric hospital settings, and cousin comparisons remained susceptible to bias from unmeasured confounding and may have been limited in capturing temporal and familial heterogeneity.
DISCLOSURES:
This study was funded by the Swedish Research Council for Health, Working Life and Welfare and the Heart and Lung Foundation. Wang reported having no relevant financial relationships. The other investigator reported receiving grants from Forte and the Heart and Lung Foundation.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
TOPLINE:
Offspring of parents with mental disorders had nearly double the risk for mortality, especially from unnatural causes, compared to those with parents did not have a mental disorder, a new Swedish cohort study showed. Additionally, mortality risk was highest when both parents had mental disorders but was not affected by the sex of the affected parent.
METHODOLOGY:
- A nationwide register-based cohort study in Sweden included more than 3.5 million individuals born between 1973 and 2014 (51% men); 35% had a parent with a mental disorder (13% paternal, 16% maternal, and 6% both parents).
- Mental disorder categories included alcohol or substance use, psychotic, mood, anxiety or stress-related, eating, and personality disorders and intellectual disability. Exposure timing was classified by offspring age (mean age, 15.8 years) at parental diagnosis.
- Participants were followed up from birth until death, the death of either parent, emigration (up to 2014), either parent’s emigration, or the end of 2023, whichever came first (median follow-up duration, 20.1 years).
- The main outcome was all-cause mortality; secondary outcomes were deaths from natural and unnatural causes, as well as deaths from cardiovascular disease, cancer, suicide, and unintentional injuries. Cousin comparison analyses were also conducted to account for confounding.
TAKEAWAY:
- During the follow-up, offspring exposed to parental psychiatric disorders had higher overall mortality rates than unexposed offspring (7.9 vs 3.55 per 10,000 person-years). Mortality rates due to natural causes were 4.0 vs 2.4 per 10,000 person-years and were 3.95 vs 1.1 per 10,000 person-years for mortality due to unnatural causes.
- Exposed offspring had an increased risk for mortality due to any cause (adjusted hazard ratio [aHR], 2.1), natural causes (aHR, 1.9), and unnatural causes (aHR, 2.45). Exposure was also associated with an increased risk for cardiovascular and cancer-related death, suicide, and death due to unintentional injuries. The associations remained significant, although slightly attenuated, in cousin comparison analyses.
- The highest risks for mortality were in offspring exposed at ages 1-2 years to both parents having mental disorders (HR for natural causes, 4.5; HR for unnatural causes, 5.3).
- The risk varied by the type of parental mental disorder, with HRs ranging from 1.6 for eating disorders to 2.2 for intellectual disability.
IN PRACTICE:
“Our findings highlight the need for improved surveillance, prevention, and early detection strategies to reduce the risk of premature mortality among offspring exposed to parental mental disorders. Whether additional support for families affected by mental disorders could mitigate the risk warrants further investigation,” the investigators wrote.
SOURCE:
This study was led by Hui Wang, PhD, Karolinska Institutet, Stockholm, Sweden. It was published online in JAMA Psychiatry.
LIMITATIONS:
Reliance on registry data may have led to the misclassification of parental mental disorders. The study lacked data on genetic factors, parenting quality, cohabitation, and social support, and its generalizability may have been limited. Immigration data after 2014 were unavailable, potentially leading to misclassifications of exposure and outcomes. The Patient Register did not distinguish between diagnoses made in general vs psychiatric hospital settings, and cousin comparisons remained susceptible to bias from unmeasured confounding and may have been limited in capturing temporal and familial heterogeneity.
DISCLOSURES:
This study was funded by the Swedish Research Council for Health, Working Life and Welfare and the Heart and Lung Foundation. Wang reported having no relevant financial relationships. The other investigator reported receiving grants from Forte and the Heart and Lung Foundation.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
A version of this article first appeared on Medscape.com.
MASLD/MASH Global Consensus Recommendations Address Guideline Discordance
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
The new consensus MASLD recommendations should help reconcile the “important differences” between guidelines from around the world, said Dr. Jaideep Behari, of the the University of Pittsburgh Medical Center.
Behari highlighted several points that may be underappreciated in clinical practice. “While many clinicians associate MASLD with obesity and type 2 diabetes, approximately a fifth of people living with MASLD are lean,” he said. “It may also come as a surprise to non-liver specialists that cardiovascular disease is the most common cause of mortality in patients with MASLD.”
He underscored the consensus recommendation to screen patients with type 2 diabetes, those with obesity and at least one cardiometabolic risk factor, and individuals with persistently elevated liver enzymes.
“Since many patients in the first two groups are mainly seen in primary care or endocrinology practices, physicians in these specialties need to be cognizant of these global consensus recommendations,” Behari said.
Turning to therapeutics, he described resmetirom as “a major milestone in the management of MASLD since it is the first drug approved in the US for treatment of MASH with F2 (moderate) or F3 (advanced) fibrosis.”
He noted that treatment requires careful patient selection and monitoring, including VCTE in the 8–20 kPa range, followed by serial liver injury testing. Efficacy should be assessed at 12 months, he noted, since “resmetirom was found to be effective in approximately a quarter of all treated patients in the pivotal clinical trial.”
“These limitations highlight the gaps in the treatment of MASLD/MASH and the need to continue development of other therapies,” Behari said.
Jaideep Behari, MD, PhD, AGAF, is director of the liver steatosis and metabolic wellness program at the University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. He reported research grant support from AstraZeneca, Madrigal, and recently completed research grant support from Gilead and Pfizer.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
These recommendations aim to boost guideline adherence and disease awareness, which have lagged despite a surge of national and international guidance in recent years, lead author Zobair M. Younossi, MD, of the Global NASH/MASH Council, Washington, DC, and colleagues, reported.
“Although these documents are similar in many ways, there are important differences in their recommendations, which have created some confusion within the field,” the panel wrote in Gastroenterology. “Areas of discordance among guidelines can be partly responsible for their low rate of implementation and the suboptimal awareness about this liver disease. Furthermore, these guidelines can be long and complex, making it challenging for busy clinicians to access the appropriate information quickly and efficiently.”
To address these gaps, more than 40 experts from around the world collaborated on the consensus project. The team reviewed 61 eligible documents published between 2018 and January 2025. Each guideline was evaluated across eight domains: epidemiology; screening; risk stratification using noninvasive tests (NITs); lifestyle management; treatment with existing medications; treatment with future medications; hepatocellular carcinoma (HCC) and preventive guidance; and pregnancy and pediatric populations.
Areas of discordance were advanced to a Delphi process using iterative online surveys, with a supermajority threshold of 67% required for acceptance. Four Delphi rounds were conducted, and by the end, all statements had achieved more than 90% agreement. The final recommendations were then summarized into practical algorithms for clinical use.
The results cover the full spectrum of MASLD care. For screening and diagnosis, experts agreed that individuals with type 2 diabetes, obesity plus cardiometabolic risk factors, or persistently elevated aminotransferases should be considered high risk. Alcohol thresholds were standardized, clarifying when to classify disease as MASLD, alcohol-related liver disease, or the hybrid “Met-ALD.”
For risk stratification, the panel endorsed a two-step algorithm beginning with the Fibrosis-4 (FIB-4) index, followed by vibration-controlled transient elastography (VCTE) or other NITs in patients above the threshold. This approach, the authors noted, was designed to be feasible in both primary care and specialty settings.
Lifestyle intervention remains the cornerstone of treatment, with weight-loss goals of 5% to reduce steatosis, 7%–10% to reduce inflammation, and at least 10% to improve fibrosis. To this end, the panel recommended a Mediterranean-style diet, increased physical activity, and reductions in sedentary time.
Drug therapy recommendations prioritized glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors for patients with diabetes or obesity, though these were not considered MASH-specific agents. Pioglitazone was noted as an option for diabetes management but not as direct MASH therapy. The panel did not recommend vitamin E, ursodeoxycholic acid, or omega-3 fatty acids, citing insufficient evidence.
The document also provides structured guidance on resmetirom, the first FDA-approved therapy for MASH. Its use was endorsed in patients with F2–F3 fibrosis confirmed by NITs, with safety checks at 3, 6, and 12 months, and efficacy evaluation after 1 year. Treatment futility was defined as concordant worsening across two NITs.
Preventive recommendations included hepatitis A and B vaccination and HCC surveillance every 6 months in patients with cirrhosis. Surveillance in noncirrhotic MASH was left to clinician judgment, based on individualized risk factors. Special considerations were outlined for pediatric and pregnant populations, although the evidence base in these groups remains sparse.
“Further research is required to determine the effectiveness of this algorithm in raising awareness of MASLD and its treatment,” Dr. Younossi and colleagues concluded.
The study was supported by the Global NASH/MASH Council, Inova Health System, and an unrestricted educational grant from Madrigal Pharmaceuticals. The investigators disclosed relationships with Sanofi, Gilead, AstraZeneca, and others.
FROM GASTROENTEROLOGY
Long-Term Data Support Reduced-Dose Maintenance in EoE
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
, according to a recent meta-analysis of long-term data.
These findings support keeping patients on long-term maintenance therapy to prevent relapse, lead author Alberto Barchi, MD, of IRCCS Ospedale San Raffaele, Milan, Italy, and colleagues, reported.
“Given the high relapse rate after treatment cessation, despite good initial response after induction, there is need for further information about long-term outcomes of maintenance treatments,” the investigators wrote in Clinical Gastroenterology and Hepatology. “However, few studies have focused on long-term effects of EoE therapies.”
In response, Dr. Barchi and colleagues conducted the present systematic review and meta-analysis, which included studies evaluating maintenance therapies for EoE with at least 48 weeks of follow-up. Eligible studies enrolled patients with confirmed EoE who had received an induction regimen and continued therapy long-term. The final dataset comprised 9 randomized controlled trials (RCTs) and 11 observational studies, with long-term outcomes were reported among 1,819 patients.
The primary outcome was histologic success, defined as fewer than 15 or 6 eosinophils per high-power field (HPF). Secondary outcomes included clinical and endoscopic response, treatment adherence, and safety events.
Random-effects meta-analyses were performed, with randomized trials and observational studies analyzed separately. Risk ratios for sustained remission versus placebo or induction therapy were calculated, and heterogeneity was assessed using the I² statistic. Safety outcomes included pooled rates of adverse events, severe adverse events, and treatment discontinuation.
Across 9 randomized controlled trials, swallowed topical corticosteroids (STCs) maintained histologic remission (less than 15 eosinophils/HPF) in 86% of patients, while biologics achieved a rate of 79%. At the stricter threshold of less than 6 eosinophils/HPF, remission rates for STCs and biologics were 59% and 70%, respectively.
Clinical remission rates were lower, at 58% for STCs and 59% for biologics. Endoscopic outcomes were less consistent-ly reported, but most trials showed stable or improved scores during long-term treatment.
In observational cohorts, proton pump inhibitors (PPIs) maintained histologic remission in 64% of patients and clinical remission in 80%. For STCs in the real-world setting, histologic and clinical remission rates were 49% and 51%, respectively.
Stepping down the dose of maintenance therapy—whether conventional or biologic—did not increase relapse risk (RR 1.04; 95% CI, 0.72–1.51). In contrast, treatment withdrawal was clearly associated with higher relapse rates: in pooled analyses, continuing therapy yielded nearly an 8-fold greater likelihood of sustained remission compared with discontinuation (RR 7.87; 95% CI, 4.19–14.77).
Safety signals were favorable. Severe adverse events occurred in 3% of patients in randomized trials and 5% in observational studies, while overall withdrawal rates were 10% and 4%, respectively. The most common adverse events with STCs were oropharyngeal candidiasis and reductions in morning cortisol, while biologics were mainly associated with injection-site reactions, headache, and nasopharyngitis.
“Results suggest that prolonging treatment is efficient in maintaining histologic and clinical remission, with overall drug-related safe profiles both in randomized trials and observational studies,” the investigators concluded, noting that more work is needed to determine if there is an optimal drug for maintenance therapy, and if certain patients can successfully discontinue treatment.
The investigators disclosed relationships with Pfizer, UCB Pharma, AstraZeneca, and others.
FROM GASTROENTEROLOGY