CHEST Physician

As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.

Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).

“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
 

Evolution of Avian Influenza Remains Hard to Predict

However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.

“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”

Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”

 

Preventive Measures Recommended

The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses. 

Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.” 

Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.

The report also called for consideration of preventative measures, such as vaccination of poultry flocks. 

Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
 

A version of this article appeared on Medscape.com.

As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.

Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).

“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
 

Evolution of Avian Influenza Remains Hard to Predict

However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.

“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”

Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”

 

Preventive Measures Recommended

The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses. 

Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.” 

Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.

The report also called for consideration of preventative measures, such as vaccination of poultry flocks. 

Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
 

A version of this article appeared on Medscape.com.

As avian influenza continues to spread among wild bird populations in the European Union (EU), scientists have described a wide range of factors that could drive the virus to spread efficiently among humans, thereby increasing its pandemic potential.

Although transmission of avian influenza A(H5N1) from infected birds to humans is rare, “new strains carrying potential mutations for mammalian adaptation” could occur, according to a report issued on April 3 by the European Centre for Disease Prevention and Control and the European Food Safety Authority. The analysis identified a threat of strains currently circulating outside Europe that could enter the EU and the wider European Economic Area (EEA).

“If avian A(H5N1) influenza viruses acquire the ability to spread efficiently among humans, large-scale transmission could occur due to the lack of immune defenses against H5 viruses in humans,” the report warned.
 

Evolution of Avian Influenza Remains Hard to Predict

However, despite many occurrences of human exposure to avian influenza since 2020, “no symptomatic or productive infection in a human has been identified in the EU/EEA,” the scientists stated. Furthermore, after almost three decades of human exposure to the A(H5N1) virus of the Gs/GD lineage, the virus has not yet acquired the mutations required for airborne transmissibility between humans. However, it remains “difficult to predict the evolutionary direction the virus will take in the future,” the scientists assessed.

“Clearly, humans are being exposed in the current USA cattle outbreak,” Professor James Wood, infectious disease epidemiologist at the University of Cambridge, United Kingdom, told this news organization. “But, arguably, what is more significant is how few cases there have been with this virus lineage and its close relatives, despite massive global exposures over the last 3 years. All diagnosed human cases seem to have been singletons, with no evidence of human-to-human transmission.”

Ian Jones, professor of virology at the University of Reading, United Kingdom, sees no evidence of an imminent spillover of avian influenza from birds. But he told this news organization: “The trouble is, the clock resets every minute. Every time the virus has come out of a bird and gone somewhere, the clock is reset. So you can never say that just because it hasn’t happened since whenever, it’s never going to happen.”

 

Preventive Measures Recommended

The European report recommended a range of cautionary measures that included enhanced surveillance, access to rapid diagnostics, and sharing of genetic sequence data. It urged EU authorities to work together, adopting a One Health perspective, to limit the exposure of mammals, including humans, to avian influenza viruses. 

Sarah Pitt, a microbiologist at the University of Brighton, United Kingdom, said the emphasis on authorities taking a One Health approach was sound. “You’re looking at humans, animals, plants, and the environment and how they’re all closely interacted,” she told this news organization. “Putting all those things together is actually going to be good for human health. So they’ve mentioned One Health a lot and I’m sure that’s on purpose because it’s the latest buzzword, and presumably it’s a way of getting governments to take it seriously.” 

Overall, Dr. Pitt believes the document is designed to move zoonotic infectious diseases a bit higher up the agenda. “They should have been higher up the agenda before COVID,” she said.

The report also called for consideration of preventative measures, such as vaccination of poultry flocks. 

Overall, Dr. Jones assesses the European report as “a reworking of what’s been pretty well covered over the years.” Despite extensive work by scientists in the field, he said: “I’m not sure we’re any better at predicting an emerging virus than we’ve ever been. I would point out that we didn’t spot SARS-CoV-2 coming, even though we had SARS-CoV-1 a few years earlier. Nobody spotted the 2009 pandemic from influenza, even though there was a lot of surveillance around at the time.”
 

A version of this article appeared on Medscape.com.

Benralizumab is now approved by the US Food and Drug Administration (FDA) for the treatment of asthma in children older than 6 years. 

Marketed as Fasenra, the medication first was approved in 2017 for patients aged 12 years or older. The drug is approved as a maintenance add-on for patients with severe eosinophilic asthma. 

AstraZeneca, which markets the drug, announced the approval for younger patients on April 11. 

The expanded indication was supported by a study that showed that the drug functions in the same way with younger children and their adolescent peers. The safety and tolerability were also consistent with the known profile of the medicine, the company said. 

For children who weigh ≥ 35 kg, the recommended dose is 30 mg. For patients aged 6-11 years who weigh < 35 kg, a new 10-mg dose will be available, according to the announcement. 

The drug, a monoclonal antibody that depletes eosinophils by binding to interleukin 5 receptor alpha on eosinophils, is administered by subcutaneous injection every 4 weeks for the first three doses and then every 8 weeks.

Benralizumab should not be used to treat acute asthma symptoms. Hypersensitivity reasons have occurred after administration of the drug. The most common adverse reactions include headache and pharyngitis.
 

A version of this article appeared on Medscape.com.

Benralizumab is now approved by the US Food and Drug Administration (FDA) for the treatment of asthma in children older than 6 years. 

Marketed as Fasenra, the medication first was approved in 2017 for patients aged 12 years or older. The drug is approved as a maintenance add-on for patients with severe eosinophilic asthma. 

AstraZeneca, which markets the drug, announced the approval for younger patients on April 11. 

The expanded indication was supported by a study that showed that the drug functions in the same way with younger children and their adolescent peers. The safety and tolerability were also consistent with the known profile of the medicine, the company said. 

For children who weigh ≥ 35 kg, the recommended dose is 30 mg. For patients aged 6-11 years who weigh < 35 kg, a new 10-mg dose will be available, according to the announcement. 

The drug, a monoclonal antibody that depletes eosinophils by binding to interleukin 5 receptor alpha on eosinophils, is administered by subcutaneous injection every 4 weeks for the first three doses and then every 8 weeks.

Benralizumab should not be used to treat acute asthma symptoms. Hypersensitivity reasons have occurred after administration of the drug. The most common adverse reactions include headache and pharyngitis.
 

A version of this article appeared on Medscape.com.

Benralizumab is now approved by the US Food and Drug Administration (FDA) for the treatment of asthma in children older than 6 years. 

Marketed as Fasenra, the medication first was approved in 2017 for patients aged 12 years or older. The drug is approved as a maintenance add-on for patients with severe eosinophilic asthma. 

AstraZeneca, which markets the drug, announced the approval for younger patients on April 11. 

The expanded indication was supported by a study that showed that the drug functions in the same way with younger children and their adolescent peers. The safety and tolerability were also consistent with the known profile of the medicine, the company said. 

For children who weigh ≥ 35 kg, the recommended dose is 30 mg. For patients aged 6-11 years who weigh < 35 kg, a new 10-mg dose will be available, according to the announcement. 

The drug, a monoclonal antibody that depletes eosinophils by binding to interleukin 5 receptor alpha on eosinophils, is administered by subcutaneous injection every 4 weeks for the first three doses and then every 8 weeks.

Benralizumab should not be used to treat acute asthma symptoms. Hypersensitivity reasons have occurred after administration of the drug. The most common adverse reactions include headache and pharyngitis.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

SAN DIEGO — Monitoring a patient’s circulating tumor DNA (ctDNA) can provide valuable insights on early response to targeted therapies among patients with HER2-positive cancers.

This was the main finding of new data presented by study author Razelle Kurzrock, MD, at the American Association for Cancer Research annual meeting.

“We found that on-treatment ctDNA can detect progression before standard-of-care response assessments. These data suggest that monitoring ctDNA can provide clinicians with important prognostic information that may guide treatment decisions,” Dr. Kurzrock, professor at the Medical College of Wisconsin, Milwaukee, said during her presentation.

Christos Evangelou/MDedge News

Commenting on the clinical implications of these findings during an interview, she said the results suggest that ctDNA dynamics provide an early window into predicting response to targeted therapies in patients with HER2-altered cancers, confirming previous findings of the predictive value of ctDNA in other cancer types.

“Such monitoring may be useful in clinical trials and eventually in practice,” she added.
 

Need for new methods to predict early tumor response

Limitations of standard radiographic tumor assessments present challenges in determining clinical response, particularly for patients receiving targeted therapies.

During her talk, Dr. Kurzrock explained that although targeted therapies are effective for patients with specific molecular alterations, standard imaging assessments fail to uncover molecular-level changes within tumors, limiting the ability of clinicians to accurately assess a patient’s response to targeted therapies.

“In addition to limitations with imaging, patients and physicians want to know as soon as possible whether or not the agents are effective, especially if there are side effects,” Dr. Kurzrock during an interview. She added that monitoring early response may be especially important across tumor types, as HER2 therapies are increasingly being considered in the pan-cancer setting.

Commenting on the potential use of this method in other cancer types with HER2 alterations, Pashtoon Murtaza Kasi, MD, MS, noted that since the study relied on a tumor-informed assay, it would be applicable across diverse tumor types.

“It is less about tissue type but more about that particular patient’s tumor at that instant in time for which a unique barcode is created,” said Dr. Kasi, a medical oncologist at Weill Cornell Medicine, New York, who was not involved in the study.

In an interview, he added that the shedding and biology would affect the assay’s performance for some tissue types.
 

Design of patient-specific ctDNA assays

In this retrospective study, the researchers examined ctDNA dynamics in 58 patients with various HER2-positive tumor types, including breast, colorectal, and other solid malignancies harboring HER2 alterations. All the patients received combination HER2-targeted therapy with trastuzumab and pertuzumab in the phase 2 basket trial My Pathway (NCT02091141).

By leveraging comprehensive genomic profiling of each patient’s tumor, the researchers designed personalized ctDNA assays, tracking 2-16 tumor-specific genetic variants in the patients’ blood samples. FoundationOne Tracker was used to detect and quantify ctDNA at baseline and the third cycle of therapy (cycle 3 day 1, or C3D1).

During an interview, Dr. Kurzrock explained that FoundationOne Tracker is a personalized ctDNA monitoring assay that allows for the detection of ctDNA in plasma, enabling ongoing liquid-based monitoring and highly sensitive quantification of ctDNA levels as mean tumor molecules per milliliter of plasma.

Among the 52 patients for whom personalized ctDNA assays were successfully designed, 48 (92.3%) had ctDNA data available at baseline, with a median of 100.7 tumor molecules per milliliter of plasma. Most patients (89.6%) were deemed ctDNA-positive, with a median of 119.5 tumor molecules per milliliter of plasma.
 

Changes in ctDNA levels predict patient survival

The researchers found that patients who experienced a greater than 90% decline in ctDNA levels by the third treatment cycle had significantly longer overall survival (OS) than those with less than 90% ctDNA decline or any increase. According to data presented by Dr. Kurzrock, the median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 9.4 months in the group with less than 90% decline or ctDNA increase (P = .007). These findings held true when the analysis was limited to the 14 patients with colorectal cancer, in which median OS was not reached in the group with greater than 90% decline in on-treatment ctDNA levels, versus 10.2 months in the group with less than 90% decline or ctDNA increase (P = 0.04).

Notably, the prognostic significance of ctDNA changes remained even among patients exhibiting radiographic stable disease, underscoring the limitations of relying solely on anatomic tumor measurements and highlighting the potential for ctDNA monitoring to complement standard clinical assessments. In the subset of patients with radiographic stable disease, those with a greater than 90% ctDNA decline had significantly longer OS than those with less ctDNA reduction (not reached versus 9.4 months; P = .01).

“When used as a complement to imaging, tissue-informed ctDNA monitoring with FoundationOne Tracker can provide more accuracy than imaging alone,” Dr. Kurzrock noted in an interview.

Dr. Kasi echoed Dr. Kurzrock’s enthusiasm regarding the clinical usefulness of these findings, saying, “Not only can you see very early on in whom the ctDNA is going down and clearing, but you can also tell apart within the group who has ‘stable disease’ as to who is deriving more benefit.”

The researchers also observed that increases in on-treatment ctDNA levels often preceded radiographic evidence of disease progression by a median of 1.3 months. These findings highlight the potential for ctDNA monitoring to complement standard clinical assessments, allowing us to detect treatment response and disease progression earlier than what is possible with imaging alone, Dr. Kurzrock explained during her talk. “This early warning signal could allow clinicians to intervene and modify treatment strategies before overt clinical deterioration,” she said.

In an interview, Dr. Kasi highlighted that this high sensitivity and specificity and the short half-life of the tumor-informed ctDNA assay make this liquid biopsy of great clinical value. “The short half-life of a few hours means that if you do an intervention to treat cancer with HER2-directed therapy, you can very quickly assess response to therapy way earlier than traditional radiographic methods.”

Dr. Kasi cautioned, however, that this assay would not capture whether new mutations or HER2 loss occurred at the time of resistance. “A repeat tissue biopsy or a next-generation sequencing-based plasma-only assay would be required for that,” he said.
 

Implementation of ctDNA monitoring in clinical trials

Dr. Kurzrock acknowledged that further research is needed to validate these results in larger, prospective cohorts before FoundationOne Tracker is adopted in the clinic. She noted, however, that this retrospective analysis, along with results from previous studies, provides a rationale for the use of ctDNA monitoring in clinical trials.

“In some centers like ours, ctDNA monitoring is already part of our standard of care since not only does it help from a physician standpoint to have a more accurate and early assessment of response, but patients also appreciate the information gained from ctDNA dynamics,” Dr. Kasi said in an interview. He explained that when radiographic findings are equivocal, ctDNA monitoring is an additional tool in their toolbox to help guide care.

He noted, however, that the cost is a challenge for implementing ctDNA monitoring as a complementary tool for real-time treatment response monitoring. “For serial monitoring, helping to reduce costs would be important in the long run,” he said in an interview. He added that obtaining sufficient tissue for testing using a tumor-informed assay can present a logistical challenge, at least for the first test. “You need sufficient tissue to make the barcode that you then follow along,” he explained.

“Developing guidelines through systematic studies about testing cadence would also be important. This would help establish whether ctDNA monitoring is helpful,” Dr. Kasi said in an interview. He explained that in some situations, biological variables affect the shedding and detection of ctDNA beyond the assay — in those cases, ctDNA monitoring may not be helpful. “Like any test, it is not meant for every patient or clinical question,” Dr. Kasi concluded.

Dr. Kurzrock and Dr. Kasi reported no relationships with entities whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

Statins raise the risks for increased glucose levels and the development of type 2 diabetes among people who don’t have it at baseline, but those risks are outweighed by the cardiovascular benefit, new data suggested.

The findings come from an analysis of individual participant data from a total of 23 randomized trials of statin therapy involving 154,664 individuals. In people without diabetes at baseline, statin therapy produces a dose-dependent increase in the risk for diabetes diagnosis, particularly among those whose glycemia marker levels are already at the diagnostic threshold.

Statins also tend to raise glucose levels in people who already have diabetes, but “the diabetes-related risks arising from the small changes in glycemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” wrote the authors of the Cholesterol Treatment Trialists’ (CTT) Collaboration in their paper, published online in The Lancet Diabetes & Endocrinology.

Moreover, they say, “since the effect of statin therapy on measures of glycemia within an individual is small, there is likely to be little clinical benefit in measuring glucose concentrations and A1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin. However, people should continue to be screened for diabetes and associated risk factors and have their glycemic control monitored in accordance with current clinical guidelines.”

The CTT is co-led by Christina Reith, MBChB, PhD, and David Preiss, PhD, FRCPath, MRCP, both of the Nuffield Department of Population Health, University of Oxford, England.

In an accompanying editorial, Hertzel C. Gerstein, MD, and Marie Pigeyre, MD, PhD, both of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada, noted that the decreased absolute annual incidence of life-threatening cardiovascular outcomes with statins in people at high risk for type 2 diabetes “clearly exceeds the 0.1%-1.3% per year increased absolute incidence of type 2 diabetes.”

Dr. Gerstein and Dr. Pigeyre also said “these findings emphasize the importance of holistic care. As people at risk for cardiovascular outcomes are also at risk for type 2 diabetes, any prescription of a statin should be accompanied by promoting proven strategies to prevent or delay diabetes, such as modest weight reduction and increased physical activity. Finally, these findings emphasize the importance of always being alert for harmful adverse effects, even with the most beneficial and successful preventive therapies.”
 

Statins Raise Diabetes Risk, Glucose Levels Slightly

The meta-analysis of trials in the CTT Collaboration included individual participant data from 19 double-blind randomized, controlled trials with a median follow-up of 4.3 years comparing statins with placebo in a total of 123,940 participants, including 18% who had known type 2 diabetes at randomization. Also analyzed were another four double-blind trials of lower- vs higher-intensity statins involving a total of 30,724 participants followed for a median of 4.9 years, with 15% having diabetes at baseline.

In the 19 trials of low- or moderate-intensity statins vs placebo, statins resulted in a significant 10% increase in new-onset diabetes compared with placebo (rate ratio, 1.10), while high-intensity statins raised the risk by an also significant 36% (1.36). This translated to a mean absolute excess of 0.12% per year of treatment.

Compared with less intensive statin therapy, more intensive statin therapy resulted in a significant 10% proportional increase in new-onset diabetes (1.10), giving an absolute annual excess of 0.22%.

In the statin vs placebo trials, differences in A1c values from placebo were 0.06 percentage points higher for low- or moderate-intensity statins and 0.08 points greater for high-intensity statins.

Nearly two thirds (62%) of the excess cases of new-onset diabetes occurred among participants in the highest quarter of the baseline glycemia distribution for both low-intensity or moderate-intensity and high-intensity statin therapy.

And among participants who already had diabetes at baseline, there was a significant 10% relative increase in worsening glycemia (defined by adverse glycemic event, A1c increase of ≥ 0.5 percentage points, or medication escalation) with low- or moderate-intensity statins compared with placebo and a 24% relative increase in the high-intensity trials.

The Nuffield Department of Population Health has an explicit policy of not accepting any personal honoraria payments directly or indirectly from the pharmaceutical and food industries. It seeks reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings. Dr. Reith reported receiving funding to the University of Oxford from the UK National Institute for Health and Care Research Health Technology Assessment Programme and holding unpaid roles on the Clinical Data Interchange Standards Consortium as a board member and WHO as a scientific advisor. Dr. Preiss reported receiving funding to his research institution (but no personal funding) from Novartis for the ORION 4 trial of inclisiran, Novo Nordisk for the ASCEND PLUS trial of semaglutide, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial and being a committee member for a National Institute for Health and Care Excellence guideline.

Dr. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reported research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing medical education grants to McMaster University from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig Pharma, Sanofi, and Jiangsu Hanson; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Pfizer, Carbon Brand, Sanofi, Kowa, and Hanmi. Pigeyre had no disclosures.
 

A version of this article appeared on Medscape.com.

Statins raise the risks for increased glucose levels and the development of type 2 diabetes among people who don’t have it at baseline, but those risks are outweighed by the cardiovascular benefit, new data suggested.

The findings come from an analysis of individual participant data from a total of 23 randomized trials of statin therapy involving 154,664 individuals. In people without diabetes at baseline, statin therapy produces a dose-dependent increase in the risk for diabetes diagnosis, particularly among those whose glycemia marker levels are already at the diagnostic threshold.

Statins also tend to raise glucose levels in people who already have diabetes, but “the diabetes-related risks arising from the small changes in glycemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” wrote the authors of the Cholesterol Treatment Trialists’ (CTT) Collaboration in their paper, published online in The Lancet Diabetes & Endocrinology.

Moreover, they say, “since the effect of statin therapy on measures of glycemia within an individual is small, there is likely to be little clinical benefit in measuring glucose concentrations and A1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin. However, people should continue to be screened for diabetes and associated risk factors and have their glycemic control monitored in accordance with current clinical guidelines.”

The CTT is co-led by Christina Reith, MBChB, PhD, and David Preiss, PhD, FRCPath, MRCP, both of the Nuffield Department of Population Health, University of Oxford, England.

In an accompanying editorial, Hertzel C. Gerstein, MD, and Marie Pigeyre, MD, PhD, both of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada, noted that the decreased absolute annual incidence of life-threatening cardiovascular outcomes with statins in people at high risk for type 2 diabetes “clearly exceeds the 0.1%-1.3% per year increased absolute incidence of type 2 diabetes.”

Dr. Gerstein and Dr. Pigeyre also said “these findings emphasize the importance of holistic care. As people at risk for cardiovascular outcomes are also at risk for type 2 diabetes, any prescription of a statin should be accompanied by promoting proven strategies to prevent or delay diabetes, such as modest weight reduction and increased physical activity. Finally, these findings emphasize the importance of always being alert for harmful adverse effects, even with the most beneficial and successful preventive therapies.”
 

Statins Raise Diabetes Risk, Glucose Levels Slightly

The meta-analysis of trials in the CTT Collaboration included individual participant data from 19 double-blind randomized, controlled trials with a median follow-up of 4.3 years comparing statins with placebo in a total of 123,940 participants, including 18% who had known type 2 diabetes at randomization. Also analyzed were another four double-blind trials of lower- vs higher-intensity statins involving a total of 30,724 participants followed for a median of 4.9 years, with 15% having diabetes at baseline.

In the 19 trials of low- or moderate-intensity statins vs placebo, statins resulted in a significant 10% increase in new-onset diabetes compared with placebo (rate ratio, 1.10), while high-intensity statins raised the risk by an also significant 36% (1.36). This translated to a mean absolute excess of 0.12% per year of treatment.

Compared with less intensive statin therapy, more intensive statin therapy resulted in a significant 10% proportional increase in new-onset diabetes (1.10), giving an absolute annual excess of 0.22%.

In the statin vs placebo trials, differences in A1c values from placebo were 0.06 percentage points higher for low- or moderate-intensity statins and 0.08 points greater for high-intensity statins.

Nearly two thirds (62%) of the excess cases of new-onset diabetes occurred among participants in the highest quarter of the baseline glycemia distribution for both low-intensity or moderate-intensity and high-intensity statin therapy.

And among participants who already had diabetes at baseline, there was a significant 10% relative increase in worsening glycemia (defined by adverse glycemic event, A1c increase of ≥ 0.5 percentage points, or medication escalation) with low- or moderate-intensity statins compared with placebo and a 24% relative increase in the high-intensity trials.

The Nuffield Department of Population Health has an explicit policy of not accepting any personal honoraria payments directly or indirectly from the pharmaceutical and food industries. It seeks reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings. Dr. Reith reported receiving funding to the University of Oxford from the UK National Institute for Health and Care Research Health Technology Assessment Programme and holding unpaid roles on the Clinical Data Interchange Standards Consortium as a board member and WHO as a scientific advisor. Dr. Preiss reported receiving funding to his research institution (but no personal funding) from Novartis for the ORION 4 trial of inclisiran, Novo Nordisk for the ASCEND PLUS trial of semaglutide, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial and being a committee member for a National Institute for Health and Care Excellence guideline.

Dr. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reported research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing medical education grants to McMaster University from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig Pharma, Sanofi, and Jiangsu Hanson; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Pfizer, Carbon Brand, Sanofi, Kowa, and Hanmi. Pigeyre had no disclosures.
 

A version of this article appeared on Medscape.com.

Statins raise the risks for increased glucose levels and the development of type 2 diabetes among people who don’t have it at baseline, but those risks are outweighed by the cardiovascular benefit, new data suggested.

The findings come from an analysis of individual participant data from a total of 23 randomized trials of statin therapy involving 154,664 individuals. In people without diabetes at baseline, statin therapy produces a dose-dependent increase in the risk for diabetes diagnosis, particularly among those whose glycemia marker levels are already at the diagnostic threshold.

Statins also tend to raise glucose levels in people who already have diabetes, but “the diabetes-related risks arising from the small changes in glycemia resulting from statin therapy are greatly outweighed by the benefits of statins on major vascular events when the direct clinical consequences of these outcomes are taken into consideration,” wrote the authors of the Cholesterol Treatment Trialists’ (CTT) Collaboration in their paper, published online in The Lancet Diabetes & Endocrinology.

Moreover, they say, “since the effect of statin therapy on measures of glycemia within an individual is small, there is likely to be little clinical benefit in measuring glucose concentrations and A1c values routinely after starting statin therapy with the aim of making comparisons to values taken before the initiation of a statin. However, people should continue to be screened for diabetes and associated risk factors and have their glycemic control monitored in accordance with current clinical guidelines.”

The CTT is co-led by Christina Reith, MBChB, PhD, and David Preiss, PhD, FRCPath, MRCP, both of the Nuffield Department of Population Health, University of Oxford, England.

In an accompanying editorial, Hertzel C. Gerstein, MD, and Marie Pigeyre, MD, PhD, both of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada, noted that the decreased absolute annual incidence of life-threatening cardiovascular outcomes with statins in people at high risk for type 2 diabetes “clearly exceeds the 0.1%-1.3% per year increased absolute incidence of type 2 diabetes.”

Dr. Gerstein and Dr. Pigeyre also said “these findings emphasize the importance of holistic care. As people at risk for cardiovascular outcomes are also at risk for type 2 diabetes, any prescription of a statin should be accompanied by promoting proven strategies to prevent or delay diabetes, such as modest weight reduction and increased physical activity. Finally, these findings emphasize the importance of always being alert for harmful adverse effects, even with the most beneficial and successful preventive therapies.”
 

Statins Raise Diabetes Risk, Glucose Levels Slightly

The meta-analysis of trials in the CTT Collaboration included individual participant data from 19 double-blind randomized, controlled trials with a median follow-up of 4.3 years comparing statins with placebo in a total of 123,940 participants, including 18% who had known type 2 diabetes at randomization. Also analyzed were another four double-blind trials of lower- vs higher-intensity statins involving a total of 30,724 participants followed for a median of 4.9 years, with 15% having diabetes at baseline.

In the 19 trials of low- or moderate-intensity statins vs placebo, statins resulted in a significant 10% increase in new-onset diabetes compared with placebo (rate ratio, 1.10), while high-intensity statins raised the risk by an also significant 36% (1.36). This translated to a mean absolute excess of 0.12% per year of treatment.

Compared with less intensive statin therapy, more intensive statin therapy resulted in a significant 10% proportional increase in new-onset diabetes (1.10), giving an absolute annual excess of 0.22%.

In the statin vs placebo trials, differences in A1c values from placebo were 0.06 percentage points higher for low- or moderate-intensity statins and 0.08 points greater for high-intensity statins.

Nearly two thirds (62%) of the excess cases of new-onset diabetes occurred among participants in the highest quarter of the baseline glycemia distribution for both low-intensity or moderate-intensity and high-intensity statin therapy.

And among participants who already had diabetes at baseline, there was a significant 10% relative increase in worsening glycemia (defined by adverse glycemic event, A1c increase of ≥ 0.5 percentage points, or medication escalation) with low- or moderate-intensity statins compared with placebo and a 24% relative increase in the high-intensity trials.

The Nuffield Department of Population Health has an explicit policy of not accepting any personal honoraria payments directly or indirectly from the pharmaceutical and food industries. It seeks reimbursement to the University of Oxford for the costs of travel and accommodation to participate in scientific meetings. Dr. Reith reported receiving funding to the University of Oxford from the UK National Institute for Health and Care Research Health Technology Assessment Programme and holding unpaid roles on the Clinical Data Interchange Standards Consortium as a board member and WHO as a scientific advisor. Dr. Preiss reported receiving funding to his research institution (but no personal funding) from Novartis for the ORION 4 trial of inclisiran, Novo Nordisk for the ASCEND PLUS trial of semaglutide, and Boehringer Ingelheim and Eli Lilly for the EMPA-KIDNEY trial and being a committee member for a National Institute for Health and Care Excellence guideline.

Dr. Gerstein holds the McMaster-Sanofi Population Health Institute Chair in Diabetes Research and Care. He reported research grants from Eli Lilly, AstraZeneca, Novo Nordisk, Hanmi, and Merck; continuing medical education grants to McMaster University from Eli Lilly, Abbott, Sanofi, Novo Nordisk, and Boehringer Ingelheim; honoraria for speaking from AstraZeneca, Eli Lilly, Novo Nordisk, DKSH, Zuellig Pharma, Sanofi, and Jiangsu Hanson; and consulting fees from Abbott, Eli Lilly, Novo Nordisk, Pfizer, Carbon Brand, Sanofi, Kowa, and Hanmi. Pigeyre had no disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In people with type 2 diabetes (T2D), higher levels of arm and trunk fat are associated with an increased risk for cardiovascular disease (CVD) and mortality, while higher levels of leg fat are associated with a reduced risk for these conditions.

METHODOLOGY:

• People with T2D have a twofold to fourfold higher risk for CVD and mortality, and evidence shows obesity management helps delay complications and premature death, but an elevated body mass index (BMI) may be insufficient to measure obesity.
• In the “obesity paradox,” people with elevated BMI may have a lower CVD risk than people of normal weight.
• Researchers prospectively investigated how regional body fat accumulation was associated with CVD risk in 21,472 people with T2D (mean age, 58.9 years; 60.7% men; BMI about 29-33) from the UK Biobank (2006-2010), followed up for a median of 7.7 years.
• The regional body fat distribution in arms, trunk, and legs was assessed using bioelectrical impedance analysis.
• The primary outcomes were the incidence of CVD, all-cause mortality, and CVD mortality.

TAKEAWAY:

• Participants in the highest quartile of arm fat percentage (multivariate-adjusted hazard ratio [HR], 1.63; 95% CI, 1.29-2.05) and trunk fat percentage (HR, 1.27; 95% CI, 1.06-1.52) were at a higher risk for CVD than those in the lowest quartile.
• However, participants in the highest quartile of leg fat percentage had a lower risk for CVD than those in the lowest quartile (HR, 0.72; 95% CI, 0.58-0.90).
• A nonlinear relationship was observed between higher leg fat percentage and lower CVD risk and between higher trunk fat percentage and higher CVD risk, whereas a linear relationship was noted between higher arm fat percentage and higher CVD risk.
• The patterns of association were similar for both all-cause mortality and CVD mortality. Overall patterns were similar for men and women.

IN PRACTICE:

“Our findings add to the understanding of body fat distribution in patients with T2D, which highlights the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among patients with T2D,” wrote the authors.

SOURCE:

The study led by Zixin Qiu, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

As body fat was measured only once at the beginning of the study, its changing association over time could not be assessed. Moreover, the findings were primarily based on predominantly White UK adults, potentially restricting their generalizability to other population groups. Furthermore, diabetes was diagnosed using self-reported medical history, medication, and hemoglobin A1c levels, implying that some cases may have gone undetected at baseline. 

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Hubei Province Science Fund for Distinguished Young Scholars, and Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with type 2 diabetes (T2D), higher levels of arm and trunk fat are associated with an increased risk for cardiovascular disease (CVD) and mortality, while higher levels of leg fat are associated with a reduced risk for these conditions.

METHODOLOGY:

• People with T2D have a twofold to fourfold higher risk for CVD and mortality, and evidence shows obesity management helps delay complications and premature death, but an elevated body mass index (BMI) may be insufficient to measure obesity.
• In the “obesity paradox,” people with elevated BMI may have a lower CVD risk than people of normal weight.
• Researchers prospectively investigated how regional body fat accumulation was associated with CVD risk in 21,472 people with T2D (mean age, 58.9 years; 60.7% men; BMI about 29-33) from the UK Biobank (2006-2010), followed up for a median of 7.7 years.
• The regional body fat distribution in arms, trunk, and legs was assessed using bioelectrical impedance analysis.
• The primary outcomes were the incidence of CVD, all-cause mortality, and CVD mortality.

TAKEAWAY:

• Participants in the highest quartile of arm fat percentage (multivariate-adjusted hazard ratio [HR], 1.63; 95% CI, 1.29-2.05) and trunk fat percentage (HR, 1.27; 95% CI, 1.06-1.52) were at a higher risk for CVD than those in the lowest quartile.
• However, participants in the highest quartile of leg fat percentage had a lower risk for CVD than those in the lowest quartile (HR, 0.72; 95% CI, 0.58-0.90).
• A nonlinear relationship was observed between higher leg fat percentage and lower CVD risk and between higher trunk fat percentage and higher CVD risk, whereas a linear relationship was noted between higher arm fat percentage and higher CVD risk.
• The patterns of association were similar for both all-cause mortality and CVD mortality. Overall patterns were similar for men and women.

IN PRACTICE:

“Our findings add to the understanding of body fat distribution in patients with T2D, which highlights the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among patients with T2D,” wrote the authors.

SOURCE:

The study led by Zixin Qiu, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

As body fat was measured only once at the beginning of the study, its changing association over time could not be assessed. Moreover, the findings were primarily based on predominantly White UK adults, potentially restricting their generalizability to other population groups. Furthermore, diabetes was diagnosed using self-reported medical history, medication, and hemoglobin A1c levels, implying that some cases may have gone undetected at baseline. 

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Hubei Province Science Fund for Distinguished Young Scholars, and Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with type 2 diabetes (T2D), higher levels of arm and trunk fat are associated with an increased risk for cardiovascular disease (CVD) and mortality, while higher levels of leg fat are associated with a reduced risk for these conditions.

METHODOLOGY:

• People with T2D have a twofold to fourfold higher risk for CVD and mortality, and evidence shows obesity management helps delay complications and premature death, but an elevated body mass index (BMI) may be insufficient to measure obesity.
• In the “obesity paradox,” people with elevated BMI may have a lower CVD risk than people of normal weight.
• Researchers prospectively investigated how regional body fat accumulation was associated with CVD risk in 21,472 people with T2D (mean age, 58.9 years; 60.7% men; BMI about 29-33) from the UK Biobank (2006-2010), followed up for a median of 7.7 years.
• The regional body fat distribution in arms, trunk, and legs was assessed using bioelectrical impedance analysis.
• The primary outcomes were the incidence of CVD, all-cause mortality, and CVD mortality.

TAKEAWAY:

• Participants in the highest quartile of arm fat percentage (multivariate-adjusted hazard ratio [HR], 1.63; 95% CI, 1.29-2.05) and trunk fat percentage (HR, 1.27; 95% CI, 1.06-1.52) were at a higher risk for CVD than those in the lowest quartile.
• However, participants in the highest quartile of leg fat percentage had a lower risk for CVD than those in the lowest quartile (HR, 0.72; 95% CI, 0.58-0.90).
• A nonlinear relationship was observed between higher leg fat percentage and lower CVD risk and between higher trunk fat percentage and higher CVD risk, whereas a linear relationship was noted between higher arm fat percentage and higher CVD risk.
• The patterns of association were similar for both all-cause mortality and CVD mortality. Overall patterns were similar for men and women.

IN PRACTICE:

“Our findings add to the understanding of body fat distribution in patients with T2D, which highlights the importance of considering both the amount and the location of body fat when assessing CVD and mortality risk among patients with T2D,” wrote the authors.

SOURCE:

The study led by Zixin Qiu, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

As body fat was measured only once at the beginning of the study, its changing association over time could not be assessed. Moreover, the findings were primarily based on predominantly White UK adults, potentially restricting their generalizability to other population groups. Furthermore, diabetes was diagnosed using self-reported medical history, medication, and hemoglobin A1c levels, implying that some cases may have gone undetected at baseline. 

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Hubei Province Science Fund for Distinguished Young Scholars, and Fundamental Research Funds for the Central Universities. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

It should come as no surprise that when physicians speak out on social and political issues, there is sometimes a backlash. This can range from the typical trolling that occurs online to rarer cases of professional penalties. Two doctors were fired by NYU Langone Health late last year after they posted social media messages about the Israel-Hamas war. Still, many physicians are not only willing to stand up for what they believe in, but they see it as an essential part of their profession. 
"We're now at a place where doctors need to engage in public advocacy as an urgent part of our job," wrote Rob Davidson, MD, an emergency department physician, at the onslaught of the COVID-19 pandemic. In an Op-Ed piece for The Guardian, Dr. Davidson noted how the virus forced many physicians into becoming "activist doctors," calling for adequate personal protective equipment and correcting misinformation. "What we want above all is for the administration to listen to doctors, nurses, and frontline health workers - and stop playing politics," he wrote. 

'It's Not About Being Political' 

The intersection of medicine and politics is hardly new. Doctors frequently testify before Congress, sharing their expertise on issues concerning public health. This, however, isn't the same as "playing politics." 
"I'm not taking political stances," said Megan Ranney, MD, Dean of the Yale School of Public Health. "Rather, I'm using science to inform best practices, and I'm vocal around the area where I have expertise where we could do collectively better." 
Dr. Ranney's work to end firearm injury and death garnered particular attention when she co-authored an open letter to the National Rifle Association (NRA) in 2018. She wrote the letter in response to a tweet by the organization, admonishing physicians to "stay in their lane" when it comes to gun control.  
Dr. Ranney's letter discussed gun violence as a public health crisis and urged the NRA to "be part of the solution" by joining the collective effort to reduce firearm injury and death through research, education, and advocacy. "We are not anti-gun," she stated. "We are anti-bullet hole," adding that "almost half of doctors own guns." 
The NRA disagreed. When Dr. Ranney testified before Congress during a hearing on gun violence in 2023, NRA spokesperson Billy McLaughlin condemned her testimony as an effort to "dismantle the Second Amendment," calling Dr. Ranney "a known gun control extremist." 
"If you actually read what I write, or if you actually listen to what I say, I'm not saying things on behalf of one political party or another," said Dr. Ranney. "It's not about being political. It's about recognizing our role in describing what's happening and making it clear for the world to see. Showing where, based off of data, there may be a better path to improve health and wellbeing." 
In spite of the backlash, Dr. Ranney has no regrets about being an activist. "In the current media landscape, folks love to slap labels on people that may or may not be accurate. To me, what matters isn't where I land with a particular politician or political party, but how the work that I do improves health for populations." 

When the Need to Act Outweighs the Fear 

Laura Andreson, DO, an ob.gyn, took activism a step further when she joined a group of women in Tennessee to file a suit against the state, the attorney general, and the state board of medical examiners. The issue was the Tennessee's abortion ban, which the suit claimed prevented women from getting "necessary and potentially life-saving medical care."  
Dr. Andreson, who says she was "not at all" politically active in the past, began to realize how the abortion ban could drastically affect her profession and her patients. "I don't know what flipped in me, but I just felt like I could do this," she said. 
Like Dr. Ranney, Dr. Andreson has been as visible as she has been vocal, giving press conferences and interviews, but she acknowledges she has some fears about safety. In fact, after filing the lawsuit, the Center for Reproductive Rights recommended that she go to a website, DeleteMe, that removes personal data from the internet, making it more difficult for people to find her information. "But my need to do this and my desire to do this is stronger than my fears," she added. 
Dr. Andreson, who is part of a small practice, did check with both her coworkers and the hospital administration before moving forward with the lawsuit. She was relieved to find that she had the support of her practice and that there wasn't anything in the hospital bylaws to prevent her from filing the lawsuit. "But the people in the bigger institutions who probably have an even better expert base than I do, they are handcuffed," she said. 
It has been, in Dr. Andreson's words, "a little uncomfortable" being on the board of the Tennessee Medical Association when the Tennessee Board of Medical Examiners is part of the lawsuit. "We're all members of the same group," she said. "But I'm not suing them as individuals; I'm suing them as an entity that is under our government." 
Dr. Andreson said most people have been supportive of her activist work, though she admitted to feeling frustrated when she encounters apathy from fellow ob.gyns. She got little response when she circulated information explaining the abortion laws and trying to get others involved. But she still sees education as being a key part of making change happen.  
"I think advocacy, as someone who is considered a responsible, trustworthy person by your community, is important, because you can sway some people just by educating them," she said. 

Fighting Inequities in Medicine and Beyond 

Christina Chen, MD, says she felt very supported by her medical community at the Mayo Clinic in Rochester, Minnesota, when she and 16 other Asian American physicians posted a video on Instagram in 2020 highlighting increased violence and harassment of Asian Americans during COVID-19. It soon went viral, and the Mayo Clinic distributed it across their social media channels. The only negative repercussions Mayo faced were a few posts on social media saying that politics should not be brought into the healthcare space. Dr. Chen disagrees. 
"Social issues and political decisions have direct impact on the health of our communities," Dr. Chen said. "We know that we still have a long way to go to solve health inequities, which is a public health problem, and we all play a huge role in voicing our concerns." 
Activism, however, seems to be more complicated when it involves physicians being critical of inequities within the medical field. Nephrologist, Vanessa Grubbs, MD, MPH, founded the nonprofit Black Doc Village in 2022 to raise awareness about the wrongful dismissal of Black residents and expand the Black physician workforce. 
Dr. Grubbs said that the medical community has not been supportive of her activism. "The reason why I'm no longer in academia is in part because they got very upset with me tweeting about how some trainees are biased in their treatment of attendings," she said. "Senior White men attendings are often treated very differently than junior women of color faculty." 
Dr. Grubbs also expressed her views in 2020 essay in the New England Journal of Medicine where she criticized academic medical institutions for ignoring systemic racism, paying lip service to diversity, equity, and inclusion, and staying "deafeningly silent" when issues of racism are raised. 
Today, Black Doc Village is focused on conducting research that can be used to change policy. And Dr. Grubbs now has the full support of her colleagues at West Oakland Health, in Oakland, California, which aspires to advance the Bay Area Black community's health and dignity. "So, no one here has a problem with me speaking out," she added. 
The emphasis on data-driven activism as opposed to "playing politics," is a recurring theme for many physicians who publicly engage with social issues. 
"It's not partisan," Dr. Ranney said. "Rather, it's a commitment to translating science into actionable steps that can be used regardless of what political party you are in. My job is not to be on one side or the other, but to advance human health." These doctors challenge their critics to explain how such a goal is outside their purview. 
A version of this article first appeared on Medscape.com.

It should come as no surprise that when physicians speak out on social and political issues, there is sometimes a backlash. This can range from the typical trolling that occurs online to rarer cases of professional penalties. Two doctors were fired by NYU Langone Health late last year after they posted social media messages about the Israel-Hamas war. Still, many physicians are not only willing to stand up for what they believe in, but they see it as an essential part of their profession. 
"We're now at a place where doctors need to engage in public advocacy as an urgent part of our job," wrote Rob Davidson, MD, an emergency department physician, at the onslaught of the COVID-19 pandemic. In an Op-Ed piece for The Guardian, Dr. Davidson noted how the virus forced many physicians into becoming "activist doctors," calling for adequate personal protective equipment and correcting misinformation. "What we want above all is for the administration to listen to doctors, nurses, and frontline health workers - and stop playing politics," he wrote. 

'It's Not About Being Political' 

The intersection of medicine and politics is hardly new. Doctors frequently testify before Congress, sharing their expertise on issues concerning public health. This, however, isn't the same as "playing politics." 
"I'm not taking political stances," said Megan Ranney, MD, Dean of the Yale School of Public Health. "Rather, I'm using science to inform best practices, and I'm vocal around the area where I have expertise where we could do collectively better." 
Dr. Ranney's work to end firearm injury and death garnered particular attention when she co-authored an open letter to the National Rifle Association (NRA) in 2018. She wrote the letter in response to a tweet by the organization, admonishing physicians to "stay in their lane" when it comes to gun control.  
Dr. Ranney's letter discussed gun violence as a public health crisis and urged the NRA to "be part of the solution" by joining the collective effort to reduce firearm injury and death through research, education, and advocacy. "We are not anti-gun," she stated. "We are anti-bullet hole," adding that "almost half of doctors own guns." 
The NRA disagreed. When Dr. Ranney testified before Congress during a hearing on gun violence in 2023, NRA spokesperson Billy McLaughlin condemned her testimony as an effort to "dismantle the Second Amendment," calling Dr. Ranney "a known gun control extremist." 
"If you actually read what I write, or if you actually listen to what I say, I'm not saying things on behalf of one political party or another," said Dr. Ranney. "It's not about being political. It's about recognizing our role in describing what's happening and making it clear for the world to see. Showing where, based off of data, there may be a better path to improve health and wellbeing." 
In spite of the backlash, Dr. Ranney has no regrets about being an activist. "In the current media landscape, folks love to slap labels on people that may or may not be accurate. To me, what matters isn't where I land with a particular politician or political party, but how the work that I do improves health for populations." 

When the Need to Act Outweighs the Fear 

Laura Andreson, DO, an ob.gyn, took activism a step further when she joined a group of women in Tennessee to file a suit against the state, the attorney general, and the state board of medical examiners. The issue was the Tennessee's abortion ban, which the suit claimed prevented women from getting "necessary and potentially life-saving medical care."  
Dr. Andreson, who says she was "not at all" politically active in the past, began to realize how the abortion ban could drastically affect her profession and her patients. "I don't know what flipped in me, but I just felt like I could do this," she said. 
Like Dr. Ranney, Dr. Andreson has been as visible as she has been vocal, giving press conferences and interviews, but she acknowledges she has some fears about safety. In fact, after filing the lawsuit, the Center for Reproductive Rights recommended that she go to a website, DeleteMe, that removes personal data from the internet, making it more difficult for people to find her information. "But my need to do this and my desire to do this is stronger than my fears," she added. 
Dr. Andreson, who is part of a small practice, did check with both her coworkers and the hospital administration before moving forward with the lawsuit. She was relieved to find that she had the support of her practice and that there wasn't anything in the hospital bylaws to prevent her from filing the lawsuit. "But the people in the bigger institutions who probably have an even better expert base than I do, they are handcuffed," she said. 
It has been, in Dr. Andreson's words, "a little uncomfortable" being on the board of the Tennessee Medical Association when the Tennessee Board of Medical Examiners is part of the lawsuit. "We're all members of the same group," she said. "But I'm not suing them as individuals; I'm suing them as an entity that is under our government." 
Dr. Andreson said most people have been supportive of her activist work, though she admitted to feeling frustrated when she encounters apathy from fellow ob.gyns. She got little response when she circulated information explaining the abortion laws and trying to get others involved. But she still sees education as being a key part of making change happen.  
"I think advocacy, as someone who is considered a responsible, trustworthy person by your community, is important, because you can sway some people just by educating them," she said. 

Fighting Inequities in Medicine and Beyond 

Christina Chen, MD, says she felt very supported by her medical community at the Mayo Clinic in Rochester, Minnesota, when she and 16 other Asian American physicians posted a video on Instagram in 2020 highlighting increased violence and harassment of Asian Americans during COVID-19. It soon went viral, and the Mayo Clinic distributed it across their social media channels. The only negative repercussions Mayo faced were a few posts on social media saying that politics should not be brought into the healthcare space. Dr. Chen disagrees. 
"Social issues and political decisions have direct impact on the health of our communities," Dr. Chen said. "We know that we still have a long way to go to solve health inequities, which is a public health problem, and we all play a huge role in voicing our concerns." 
Activism, however, seems to be more complicated when it involves physicians being critical of inequities within the medical field. Nephrologist, Vanessa Grubbs, MD, MPH, founded the nonprofit Black Doc Village in 2022 to raise awareness about the wrongful dismissal of Black residents and expand the Black physician workforce. 
Dr. Grubbs said that the medical community has not been supportive of her activism. "The reason why I'm no longer in academia is in part because they got very upset with me tweeting about how some trainees are biased in their treatment of attendings," she said. "Senior White men attendings are often treated very differently than junior women of color faculty." 
Dr. Grubbs also expressed her views in 2020 essay in the New England Journal of Medicine where she criticized academic medical institutions for ignoring systemic racism, paying lip service to diversity, equity, and inclusion, and staying "deafeningly silent" when issues of racism are raised. 
Today, Black Doc Village is focused on conducting research that can be used to change policy. And Dr. Grubbs now has the full support of her colleagues at West Oakland Health, in Oakland, California, which aspires to advance the Bay Area Black community's health and dignity. "So, no one here has a problem with me speaking out," she added. 
The emphasis on data-driven activism as opposed to "playing politics," is a recurring theme for many physicians who publicly engage with social issues. 
"It's not partisan," Dr. Ranney said. "Rather, it's a commitment to translating science into actionable steps that can be used regardless of what political party you are in. My job is not to be on one side or the other, but to advance human health." These doctors challenge their critics to explain how such a goal is outside their purview. 
A version of this article first appeared on Medscape.com.

It should come as no surprise that when physicians speak out on social and political issues, there is sometimes a backlash. This can range from the typical trolling that occurs online to rarer cases of professional penalties. Two doctors were fired by NYU Langone Health late last year after they posted social media messages about the Israel-Hamas war. Still, many physicians are not only willing to stand up for what they believe in, but they see it as an essential part of their profession. 
"We're now at a place where doctors need to engage in public advocacy as an urgent part of our job," wrote Rob Davidson, MD, an emergency department physician, at the onslaught of the COVID-19 pandemic. In an Op-Ed piece for The Guardian, Dr. Davidson noted how the virus forced many physicians into becoming "activist doctors," calling for adequate personal protective equipment and correcting misinformation. "What we want above all is for the administration to listen to doctors, nurses, and frontline health workers - and stop playing politics," he wrote. 

'It's Not About Being Political' 

The intersection of medicine and politics is hardly new. Doctors frequently testify before Congress, sharing their expertise on issues concerning public health. This, however, isn't the same as "playing politics." 
"I'm not taking political stances," said Megan Ranney, MD, Dean of the Yale School of Public Health. "Rather, I'm using science to inform best practices, and I'm vocal around the area where I have expertise where we could do collectively better." 
Dr. Ranney's work to end firearm injury and death garnered particular attention when she co-authored an open letter to the National Rifle Association (NRA) in 2018. She wrote the letter in response to a tweet by the organization, admonishing physicians to "stay in their lane" when it comes to gun control.  
Dr. Ranney's letter discussed gun violence as a public health crisis and urged the NRA to "be part of the solution" by joining the collective effort to reduce firearm injury and death through research, education, and advocacy. "We are not anti-gun," she stated. "We are anti-bullet hole," adding that "almost half of doctors own guns." 
The NRA disagreed. When Dr. Ranney testified before Congress during a hearing on gun violence in 2023, NRA spokesperson Billy McLaughlin condemned her testimony as an effort to "dismantle the Second Amendment," calling Dr. Ranney "a known gun control extremist." 
"If you actually read what I write, or if you actually listen to what I say, I'm not saying things on behalf of one political party or another," said Dr. Ranney. "It's not about being political. It's about recognizing our role in describing what's happening and making it clear for the world to see. Showing where, based off of data, there may be a better path to improve health and wellbeing." 
In spite of the backlash, Dr. Ranney has no regrets about being an activist. "In the current media landscape, folks love to slap labels on people that may or may not be accurate. To me, what matters isn't where I land with a particular politician or political party, but how the work that I do improves health for populations." 

When the Need to Act Outweighs the Fear 

Laura Andreson, DO, an ob.gyn, took activism a step further when she joined a group of women in Tennessee to file a suit against the state, the attorney general, and the state board of medical examiners. The issue was the Tennessee's abortion ban, which the suit claimed prevented women from getting "necessary and potentially life-saving medical care."  
Dr. Andreson, who says she was "not at all" politically active in the past, began to realize how the abortion ban could drastically affect her profession and her patients. "I don't know what flipped in me, but I just felt like I could do this," she said. 
Like Dr. Ranney, Dr. Andreson has been as visible as she has been vocal, giving press conferences and interviews, but she acknowledges she has some fears about safety. In fact, after filing the lawsuit, the Center for Reproductive Rights recommended that she go to a website, DeleteMe, that removes personal data from the internet, making it more difficult for people to find her information. "But my need to do this and my desire to do this is stronger than my fears," she added. 
Dr. Andreson, who is part of a small practice, did check with both her coworkers and the hospital administration before moving forward with the lawsuit. She was relieved to find that she had the support of her practice and that there wasn't anything in the hospital bylaws to prevent her from filing the lawsuit. "But the people in the bigger institutions who probably have an even better expert base than I do, they are handcuffed," she said. 
It has been, in Dr. Andreson's words, "a little uncomfortable" being on the board of the Tennessee Medical Association when the Tennessee Board of Medical Examiners is part of the lawsuit. "We're all members of the same group," she said. "But I'm not suing them as individuals; I'm suing them as an entity that is under our government." 
Dr. Andreson said most people have been supportive of her activist work, though she admitted to feeling frustrated when she encounters apathy from fellow ob.gyns. She got little response when she circulated information explaining the abortion laws and trying to get others involved. But she still sees education as being a key part of making change happen.  
"I think advocacy, as someone who is considered a responsible, trustworthy person by your community, is important, because you can sway some people just by educating them," she said. 

Fighting Inequities in Medicine and Beyond 

Christina Chen, MD, says she felt very supported by her medical community at the Mayo Clinic in Rochester, Minnesota, when she and 16 other Asian American physicians posted a video on Instagram in 2020 highlighting increased violence and harassment of Asian Americans during COVID-19. It soon went viral, and the Mayo Clinic distributed it across their social media channels. The only negative repercussions Mayo faced were a few posts on social media saying that politics should not be brought into the healthcare space. Dr. Chen disagrees. 
"Social issues and political decisions have direct impact on the health of our communities," Dr. Chen said. "We know that we still have a long way to go to solve health inequities, which is a public health problem, and we all play a huge role in voicing our concerns." 
Activism, however, seems to be more complicated when it involves physicians being critical of inequities within the medical field. Nephrologist, Vanessa Grubbs, MD, MPH, founded the nonprofit Black Doc Village in 2022 to raise awareness about the wrongful dismissal of Black residents and expand the Black physician workforce. 
Dr. Grubbs said that the medical community has not been supportive of her activism. "The reason why I'm no longer in academia is in part because they got very upset with me tweeting about how some trainees are biased in their treatment of attendings," she said. "Senior White men attendings are often treated very differently than junior women of color faculty." 
Dr. Grubbs also expressed her views in 2020 essay in the New England Journal of Medicine where she criticized academic medical institutions for ignoring systemic racism, paying lip service to diversity, equity, and inclusion, and staying "deafeningly silent" when issues of racism are raised. 
Today, Black Doc Village is focused on conducting research that can be used to change policy. And Dr. Grubbs now has the full support of her colleagues at West Oakland Health, in Oakland, California, which aspires to advance the Bay Area Black community's health and dignity. "So, no one here has a problem with me speaking out," she added. 
The emphasis on data-driven activism as opposed to "playing politics," is a recurring theme for many physicians who publicly engage with social issues. 
"It's not partisan," Dr. Ranney said. "Rather, it's a commitment to translating science into actionable steps that can be used regardless of what political party you are in. My job is not to be on one side or the other, but to advance human health." These doctors challenge their critics to explain how such a goal is outside their purview. 
A version of this article first appeared on Medscape.com.

ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.

The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.

“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.” 

The study findings were published online simultaneously in the Journal of the American College of Cardiology.
 

Telemedicine Protocol

The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter. 

Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years. 

If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.

Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.

Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).

MACE rates were similar between the two groups.

At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.

The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).

Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
 

Human Element Key

In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.

However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”

Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology. 

“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”

While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”

The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.

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

ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.

The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.

“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.” 

The study findings were published online simultaneously in the Journal of the American College of Cardiology.
 

Telemedicine Protocol

The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter. 

Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years. 

If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.

Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.

Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).

MACE rates were similar between the two groups.

At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.

The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).

Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
 

Human Element Key

In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.

However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”

Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology. 

“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”

While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”

The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.

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

ATLANTA — Patients with acute coronary syndrome (ACS) who had a myocardial infarction or unstable angina and underwent percutaneous coronary intervention (PCI) had a 76% lower rate of hospital readmission after 6 months if they participated in a remote monitoring protocol compared with similar patients who had standard post-discharge care, results of a new trial suggest.

The TELE-ACS trial showed that at 6 months, telemedicine patients also had statistically significantly lower rates of post-discharge emergency department visits, unplanned coronary revascularizations, and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness. However, the rates of major adverse cardiovascular events (MACE) were similar between the two groups. The protocol included consultation with a cardiologist who reviewed home-monitoring data.

“The team was able to aid in preventing unnecessary presentations and advised the patients to seek emergency care whenever was necessary,” Nasser Alshahrani, MSc, a clinical research fellow at Imperial College London, said while presenting the results at the American College of Cardiology meeting. “The TELE-ACS protocol provided a significant reduction in readmission rates post-ACS and other adverse events.” 

The study findings were published online simultaneously in the Journal of the American College of Cardiology.
 

Telemedicine Protocol

The trial, conducted from January 2022 to April 2023, randomly assigned 337 patients to telemedicine or standard care when they were discharged after PCI and had at least one cardiovascular risk factor. The telemedicine protocol consisted of 12-lead electrocardiogram belt, an automated blood-pressure monitor, and a pulse oximeter. 

Patients in the telemedicine arm initiated the remote monitoring protocol if they thought they had cardiac symptoms. The majority (86%) were men with what the study described as “a high preponderance of cardiovascular risk factors.” Average age was 58.1 years. 

If a telemedicine patient initiated the protocol, a cardiologist remotely assessed the patient’s symptoms and channeled the patient to the appropriate care pathway, whether reassuring the patient or sending them to a primary care physician or emergency department, or to call emergency services. Patients who didn’t get a call back from the cardiologist within 15 minutes were told to seek care in the standard clinical pathway.

Telemedicine patients were given the telemonitoring package and training in how to use the devices before they were discharged. They also received three follow-up quality control calls in the first two months to ensure they were using the equipment correctly. They kept the telemonitoring equipment for 8 months, but were followed out to 9 months. Six telemedicine patients dropped out while one standard care patient withdrew from the study.

Results showed that at 6 months, telemedicine patients had statistically significantly lower rates of post-discharge emergency department visits (25% vs 37%, P < .001), unplanned coronary revascularizations (3% vs 9%, P < .01) and cardiovascular symptoms, such as chest pain, shortness of breath and dizziness (a 13% to 18% difference for each symptom, P < .01).

MACE rates were similar between the two groups.

At 9 months, 3 months after the protocol ended, 20 telemedicine patients and 50 standard-care patients were readmitted to the hospital, while 52 and 73, respectively, went to the emergency department.

The telemedicine patients also had shorter hospital stays: an average of 0.5 and 1.2 days at 6 and 9 months, respectively, vs 1.5 and 1.8 days in the standard treatment arm (P < .001 for both).

Mr. Alshahrani noted several limitations with the study, namely that 86% of participants were men, and that the intervention was only offered to people who had smartphones. “The high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training,” he added.
 

Human Element Key

In an interview from London after the presentation, lead author Ramzi Khamis, MB ChB, PhD, said, “This was quite a basic study. Really what we did was we integrated a clinical decision-making algorithm that we perfected with some quite novel but basic technology.” Future research should strive to add a home troponin test to the protocol and an artificial intelligence component, he said.

However, Dr. Khamis noted that human interaction was key to the success of the TELE-ACS trial. “The human factor is very important here and I think it would be really interesting to have a head-to-head comparison of human interaction with remote monitoring vs an AI-driven interaction,” he said. “I have my doubts that AI would be able to beat the human factor here.”

Lawrence Phillips, MD, medical director of outpatient cardiology at NYU Langone Heart, told this news organization that the study was appropriately powered to evaluate the telemedicine protocol, and that it could serve as a template for other studies of remote monitoring in cardiology. 

“I think that this study is forming the foundation of evolving telemedicine data,” he said. “It shows really interesting results, and I’m sure it’s going to be reproduced in different ways going forward.”

While other studies have shown the utility of telemedicine to decrease unnecessary hospitalizations, this study went one step further, Dr. Phillips said. “What was unique about this study was the package that they put together,” he added. “It was a combination of telehealth and being able to speak with someone when you have concerns with objective data of an electrocardiogram, blood-pressure cuff, and oxygen level assessment, which is an interesting approach having that ejective data with [a] subjective element.”

The trial received funding from the British Heart Foundation; King Khalid University, Abha, Saudi Arabia via The Saudi Arabian Cultural Bureau; Sansour Fund, Imperial Healthcare Charity; and Safwan Sobhan Fund at Imperial College London. Mr. Alshahrani and Dr. Khamis have no relevant relationships to disclose. Dr. Phillips has no relevant disclosures.

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

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

SAN DIEGO — Fewer than half of the cancer drugs approved under the US Food and Drug Administration’s (FDA’s) accelerated approval pathway between 2013 and 2017 have been shown to improve overall survival or quality of life, despite being on the US market for more than 5 years, according to a new study. 

Under the program, drugs are approved for marketing if they show benefit in surrogate markers thought to indicate efficacy. Progression-free survival, tumor response, and duration of response are the most used surrogate markers for accelerated approvals of cancer drugs. These are based largely on imaging studies that show either a stop in growth in the case of progression-free survival or tumor shrinkage in the case of tumor response. 

Following accelerated approvals, companies are then supposed to show actual clinical benefit in confirmatory trials.

The problem with relying on surrogate markers for drug approvals is that they don’t always correlate with longer survival or improved quality of life, said Edward Cliff, MBBS, who presented the findings at the American Association for Cancer Research 2024 annual meeting (abstract 918). The study was also published in JAMA to coincide with the meeting presentation.

In some cancers, these markers work well, but in others they don’t, said Dr. Cliff, a hematology trainee at Brigham and Women’s Hospital, Boston, when the work was conducted, and now a hematology fellow at the Peter MacCallum Cancer Centre in Melbourne, Australia.

To determine whether cancer drugs granted accelerated approval ultimately show an overall survival or quality of life benefit, researchers reviewed 46 cancer drugs granted accelerated approvals between 2013 and 2017. Twenty (43%) were granted full approval after demonstrating survival or quality-of-life benefits. 

Nine, however, were converted to full approvals on the basis of surrogate markers. These include a full approval for pembrolizumab in previously treated recurrent or refractory head and neck squamous cell carcinoma and a full approval for nivolumab for refractory locally advanced or metastatic urothelial carcinoma, both based on tumor response rate and duration of response.

Of the remaining 17 drugs evaluated in the trial, 10 have been withdrawn and seven do not yet have confirmatory trial results. 

The reliance on surrogate markers means that these drugs are used for treatment, covered by insurance, and added to guidelines — all without solid evidence of real-world clinical benefit, said Dr. Cliff. 

However, the goal should not be to do away with the accelerated approval process, because it sometimes does deliver powerful agents to patients quickly. Instead, Dr. Cliff told this news organization, the system needs to be improved so that “we keep the speed while getting certainty around clinical benefits” with robust and timely confirmatory trials. 

In the meantime, “clinicians should communicate with patients about any residual uncertainty of clinical benefit when they offer novel therapies,” Dr. Cliff explained. “It’s important for them to have the information.”

There has been some progress on the issue. In December 2022, the US Congress passed the Food and Drug Administration Omnibus Reform Act. Among other things, the Act requires companies to have confirmation trials underway as a condition for accelerated approval, and to provide regular reports on their progress. The Act also expedites the withdrawal process for drugs that don’t show a benefit. 

The Act has been put to the test twice recently. In February, FDA used the expedited process to remove the multiple myeloma drug melphalan flufenamide from the market. Melphalan flufenamide hadn’t been sold in the US for quite some time, so the process wasn’t contentious. 

In March, Regeneron announced that accelerated approval for the follicular and diffuse B cell lymphoma drug odronextamab has been delayed pending enrollment in a confirmatory trial. 

“There have been some promising steps,” Dr. Cliff said, but much work needs to be done. 

Study moderator Shivaani Kummar, MD, agreed, noting that “the data is showing that the confirmatory trials aren’t happening at the pace which they should.” 

But the solution is not to curtail approvals; it’s to make sure that accelerated approval commitments are met, said Dr. Kummar.

Still, “as a practicing oncologist, I welcome the accelerated pathway,” Dr. Kummar, a medical oncologist/hematologist at Oregon Health & Science University, Portland, told this news organization. “I want the availability to my patients.” 

Having drugs approved on the basis of surrogate markers doesn’t necessarily mean patients are getting ineffective therapies, Dr. Kummar noted. For instance, if an agent just shrinks the tumor, it can sometimes still be “a huge clinical benefit because it can take the symptoms away.” 

As for prescribing drugs based on accelerated approvals, she said she tells her patients that trials have been promising, but we don’t know what the long-term effects are. She and her patient then make a decision together. 

The study was funded by Arnold Ventures. Dr. Kummar reported support from several companies, including Bayer, Gilead, and others. Dr. Cliff had no disclosures. 
 

A version of this article appeared on Medscape.com.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Immersive virtual reality (VR) distraction therapy may be more effective at controlling pain in hospitalized patients with cancer than a two-dimensional guided imagery experience, suggests a new randomized controlled trial.

While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.

MedStar Health

“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”

To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
 

Study Methods and Results

Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.

“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”

The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.

“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.

Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.

“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
 

Downsides to Using VR

Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.

Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
 

Future VR Research

“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”

This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.

Dhaval Desai, MD, was teaching his 4-year-old to ride a bike after another exhausting shift at the hospital during the summer after the first COVID-19 surge. He was putting on a happy face and forcing out a “Yay!” he did not feel. The pandemic had taken its toll, and he just wanted to lie down and be alone. Realizing that he was “scraping to find joy” was when he knew something was wrong.

“I was giving, giving, giving at work a lot, and I had little left to give at home,” said Dr. Desai, director of hospital medicine at Emory Saint Joseph’s Hospital and an assistant professor of medicine at Emory University in Atlanta, Georgia.

At work, he worried about his wife managing two kids — including a newborn — during the pandemic. At home, he stressed about work and the crush of patients with COVID the hospital was grappling to handle. He was exhausted, resentful, and angry, and it was jeopardizing what mattered most to him: His home life.

“It was all colliding…I realized, OK, I’m struggling,” he said.

Dr. Desai is one of thousands of physicians across the United States who have experienced burnout and depression, exacerbated by the pandemic. After 4 years, the impact is still being felt. Medscape’s 2024 annual report on this issue found that burnout and depression among doctors — while encouragingly better than the prior year — remain higher than before COVID. For doctors caring for patients with long COVID, those suffering from the debilitating aftereffects of an infection, the sense of helplessness when recovery is elusive can also weigh heavily.

Overall, more female physicians reported feeling burned out and depressed. Experts attributed this gap to issues including fewer women in supportive leadership and mentoring roles, compensation disparities, fewer career advancement opportunities, and more responsibilities caring for children and elders.

Multiple international studies and reports have highlighted the surge in burnout experienced by physicians and healthcare workers globally during the pandemic. Even before COVID, studies found the suicide rate among male and female US physicians was higher than the general population and higher than any other profession, including the military. The risk among female physicians, in particular, was 250%-400% higher.

“That’s really, on average, one a day, and that’s really unacceptable. No one should die by suicide, but a physician who knows the risks and knows that, should never do that,” said Dr. Desai about suicides overall among doctors.

The story of Lorna Breen had rattled Dr. Desai. Dr. Breen was a Manhattan physician who died by suicide in April 2020 after grappling with the city’s devastating first wave and then contracting COVID-19 herself. While Dr. Desai did not have thoughts of suicide, he was facing his own battles. Those experiences and the stigma around mental health prompted him to write his book, Burning Out on the Covid Front Lines: A Doctor’s Memoir of Fatherhood, Race and Perseverance in the Pandemic, with the hope that it can help others like him.
 

Mental Health Stigma

But despite the body of research and growing awareness toward addressing mental health among physicians, almost four in 10 doctors are wary of revealing their personal struggles.

More than half of those surveyed in the Medscape Medical News report said they had not consulted a mental health professional before and would not do so going forward either. The fear of tarnishing their reputation or even losing their license keeps doctors silent. Advocates and groups like the Dr. Lorna Breen Heroes’ Foundation are pushing for hospitals and healthcare systems to remove and rephrase invasive and stigmatizing language around mental health in licensure, credentialing, or insurance applications.
 

Burnout Triggers: Systemic Problems, Social Tensions

Burnout can make a person feel “depleted and used up” and is characterized by extreme tiredness, low energy, frustration about work, emotional distance or numbness, and difficulty with concentration, responsibilities, or creativity. It can make an individual feel helpless, alone, defeated, cynical, and without purpose and can also cause physical symptoms such as headaches, loss of appetite, insomnia, and body aches. Unaddressed, it can lead to depression, anxiety, and a variety of physical health issues.

“We can still be highly functional and not okay,” said Dr. Desai.

For doctors, burnout often builds over time from large and small systemic problems and inefficiencies, multiplied by a dozen or more patients each day: Not enough time for documentation, complicated paperwork, navigating byzantine health and insurance systems, and hitting roadblocks. The administrative work, combined with an enormous patient load, and staffing and resource shortages create barriers to care and cuts into the amount of time they can spend providing actual care.

These existing problems worsened as patients with COVID overwhelmed hospitals and clinics. At the same time, healthcare workers worried about caring for the sick, getting infected themselves, or having multiple staff falling ill at once. As each surge came and went, backlash, hostility, abuse, and even violence toward healthcare workers also increased. The discrimination some medical staff were subjected to compounded the burnout.

“When we’re not getting the support we need as physicians and healthcare workers, that adds to burnout, and I saw that in my colleagues,” said Dr. Desai.
 

Impact of Burnout

At the Mount Sinai Center for Post-COVID Care in New York City, doctors grapple with feelings of helplessness in caring for patients with long COVID who show little sign of recovery. That emotional toll can also be difficult, said director Zijian Chen, MD, who helped launch the clinic in May 2020.

“Sometimes you’re faced with patients who you’re trying to do everything for, but they’re not just not getting better,” said Dr. Chen. “It’s really frustrating because we want everybody to get better. So, there’s that lack of fulfillment there that can cause a sense of burnout.”

While the worst outcomes and death rates initially brought on by acute infections have lessened, long COVID clinics exemplify some of the ongoing challenges within healthcare. Many operate with insufficient financial and staffing resources despite wait-lists and a steady flow of new and returning patients. Even with the demand, a number of these clinics have shuttered, leaving patients without access to much-needed medical help.

“There are clinicians who are burning out. That is definitely something that I’ve seen,” said Monica Verduzco-Gutierrez, MD, a professor and chair of the Department of Rehabilitation Medicine at the University of Texas Health Science Center in San Antonio, Texas.

“[It] takes a lot of resources for a successful long COVID clinic. A lot of special funding may be drying up and couple that with clinicians burning out, then they’re going to shut their doors.”

And it’s not just long COVID clinics. Data have shown an overall exodus in healthcare, especially during the pandemic. One study found burnout was one of the “most impactful” predictors of a physician’s intention to leave the profession during the pandemic. The loss of talent and skills during a major health crisis can put the entire system under stress, with patients ultimately suffering from poorer care.

“Healthcare system fragility and the chaos is far worse than it was before. We are continuing to be forced to do more with less,” said Dr. Desai.
 

Alleviating Burnout

While it is difficult to assess whether burnout from the pandemic is transient, experts say this is an opportunity for health institutions to learn from these experiences and implement policies and actions that can help reduce the mental health strain on staff. One study found that changes made by organizations had a bigger positive impact on reducing burnout than individual changes.

Advocates say more support staff, more work flexibility, and higher compensation would significantly ease the burden that drives burnout and depression.

In addition, half the physicians surveyed in the Medscape Medical News report felt their employers were not acknowledging how pervasive burnout is at their workplace. Having a trusted peer or leader set an example by sharing his or her own challenging experiences and saying it›s time to address these struggles can be an enormously validating step forward, said Dr. Desai. Acknowledging his own difficulties was not only a huge weight off his shoulders but also helped surpris colleagues who sought him out for counsel.

“I’m not suggesting everybody get on medication,” he said. “But talking to a therapist, acknowledging there’s issues, restructuring your life to realize something’s off, and just knowing that you’re not alone? That’s huge.”

Dr. Desai said he still faces personal challenges but is in a much better place, doing well at work and at home. He talks to a therapist, is taking medication, and has developed better coping mechanisms. He is spending more time with his family, detaching for a few hours from work-related emails, learning to draw boundaries and say no, and trying to be more present and “intentional” in connecting with colleagues and patients.

“It’s okay to not be okay,” said Dr. Desai. “It’s okay to be vulnerable and acknowledge when we can’t do more.”

Are you in a crisis? Call or text 988 or text TALK to 741741. For immediate support for healthcare professionals, as well as resources for institutions and organizations, visit: afsp.org/suicide-prevention-for-healthcare-professionals/#facts-about-mental-health-and-suicide.

A version of this article appeared on Medscape.com.

Dhaval Desai, MD, was teaching his 4-year-old to ride a bike after another exhausting shift at the hospital during the summer after the first COVID-19 surge. He was putting on a happy face and forcing out a “Yay!” he did not feel. The pandemic had taken its toll, and he just wanted to lie down and be alone. Realizing that he was “scraping to find joy” was when he knew something was wrong.

“I was giving, giving, giving at work a lot, and I had little left to give at home,” said Dr. Desai, director of hospital medicine at Emory Saint Joseph’s Hospital and an assistant professor of medicine at Emory University in Atlanta, Georgia.

At work, he worried about his wife managing two kids — including a newborn — during the pandemic. At home, he stressed about work and the crush of patients with COVID the hospital was grappling to handle. He was exhausted, resentful, and angry, and it was jeopardizing what mattered most to him: His home life.

“It was all colliding…I realized, OK, I’m struggling,” he said.

Dr. Desai is one of thousands of physicians across the United States who have experienced burnout and depression, exacerbated by the pandemic. After 4 years, the impact is still being felt. Medscape’s 2024 annual report on this issue found that burnout and depression among doctors — while encouragingly better than the prior year — remain higher than before COVID. For doctors caring for patients with long COVID, those suffering from the debilitating aftereffects of an infection, the sense of helplessness when recovery is elusive can also weigh heavily.

Overall, more female physicians reported feeling burned out and depressed. Experts attributed this gap to issues including fewer women in supportive leadership and mentoring roles, compensation disparities, fewer career advancement opportunities, and more responsibilities caring for children and elders.

Multiple international studies and reports have highlighted the surge in burnout experienced by physicians and healthcare workers globally during the pandemic. Even before COVID, studies found the suicide rate among male and female US physicians was higher than the general population and higher than any other profession, including the military. The risk among female physicians, in particular, was 250%-400% higher.

“That’s really, on average, one a day, and that’s really unacceptable. No one should die by suicide, but a physician who knows the risks and knows that, should never do that,” said Dr. Desai about suicides overall among doctors.

The story of Lorna Breen had rattled Dr. Desai. Dr. Breen was a Manhattan physician who died by suicide in April 2020 after grappling with the city’s devastating first wave and then contracting COVID-19 herself. While Dr. Desai did not have thoughts of suicide, he was facing his own battles. Those experiences and the stigma around mental health prompted him to write his book, Burning Out on the Covid Front Lines: A Doctor’s Memoir of Fatherhood, Race and Perseverance in the Pandemic, with the hope that it can help others like him.
 

Mental Health Stigma

But despite the body of research and growing awareness toward addressing mental health among physicians, almost four in 10 doctors are wary of revealing their personal struggles.

More than half of those surveyed in the Medscape Medical News report said they had not consulted a mental health professional before and would not do so going forward either. The fear of tarnishing their reputation or even losing their license keeps doctors silent. Advocates and groups like the Dr. Lorna Breen Heroes’ Foundation are pushing for hospitals and healthcare systems to remove and rephrase invasive and stigmatizing language around mental health in licensure, credentialing, or insurance applications.
 

Burnout Triggers: Systemic Problems, Social Tensions

Burnout can make a person feel “depleted and used up” and is characterized by extreme tiredness, low energy, frustration about work, emotional distance or numbness, and difficulty with concentration, responsibilities, or creativity. It can make an individual feel helpless, alone, defeated, cynical, and without purpose and can also cause physical symptoms such as headaches, loss of appetite, insomnia, and body aches. Unaddressed, it can lead to depression, anxiety, and a variety of physical health issues.

“We can still be highly functional and not okay,” said Dr. Desai.

For doctors, burnout often builds over time from large and small systemic problems and inefficiencies, multiplied by a dozen or more patients each day: Not enough time for documentation, complicated paperwork, navigating byzantine health and insurance systems, and hitting roadblocks. The administrative work, combined with an enormous patient load, and staffing and resource shortages create barriers to care and cuts into the amount of time they can spend providing actual care.

These existing problems worsened as patients with COVID overwhelmed hospitals and clinics. At the same time, healthcare workers worried about caring for the sick, getting infected themselves, or having multiple staff falling ill at once. As each surge came and went, backlash, hostility, abuse, and even violence toward healthcare workers also increased. The discrimination some medical staff were subjected to compounded the burnout.

“When we’re not getting the support we need as physicians and healthcare workers, that adds to burnout, and I saw that in my colleagues,” said Dr. Desai.
 

Impact of Burnout

At the Mount Sinai Center for Post-COVID Care in New York City, doctors grapple with feelings of helplessness in caring for patients with long COVID who show little sign of recovery. That emotional toll can also be difficult, said director Zijian Chen, MD, who helped launch the clinic in May 2020.

“Sometimes you’re faced with patients who you’re trying to do everything for, but they’re not just not getting better,” said Dr. Chen. “It’s really frustrating because we want everybody to get better. So, there’s that lack of fulfillment there that can cause a sense of burnout.”

While the worst outcomes and death rates initially brought on by acute infections have lessened, long COVID clinics exemplify some of the ongoing challenges within healthcare. Many operate with insufficient financial and staffing resources despite wait-lists and a steady flow of new and returning patients. Even with the demand, a number of these clinics have shuttered, leaving patients without access to much-needed medical help.

“There are clinicians who are burning out. That is definitely something that I’ve seen,” said Monica Verduzco-Gutierrez, MD, a professor and chair of the Department of Rehabilitation Medicine at the University of Texas Health Science Center in San Antonio, Texas.

“[It] takes a lot of resources for a successful long COVID clinic. A lot of special funding may be drying up and couple that with clinicians burning out, then they’re going to shut their doors.”

And it’s not just long COVID clinics. Data have shown an overall exodus in healthcare, especially during the pandemic. One study found burnout was one of the “most impactful” predictors of a physician’s intention to leave the profession during the pandemic. The loss of talent and skills during a major health crisis can put the entire system under stress, with patients ultimately suffering from poorer care.

“Healthcare system fragility and the chaos is far worse than it was before. We are continuing to be forced to do more with less,” said Dr. Desai.
 

Alleviating Burnout

While it is difficult to assess whether burnout from the pandemic is transient, experts say this is an opportunity for health institutions to learn from these experiences and implement policies and actions that can help reduce the mental health strain on staff. One study found that changes made by organizations had a bigger positive impact on reducing burnout than individual changes.

Advocates say more support staff, more work flexibility, and higher compensation would significantly ease the burden that drives burnout and depression.

In addition, half the physicians surveyed in the Medscape Medical News report felt their employers were not acknowledging how pervasive burnout is at their workplace. Having a trusted peer or leader set an example by sharing his or her own challenging experiences and saying it›s time to address these struggles can be an enormously validating step forward, said Dr. Desai. Acknowledging his own difficulties was not only a huge weight off his shoulders but also helped surpris colleagues who sought him out for counsel.

“I’m not suggesting everybody get on medication,” he said. “But talking to a therapist, acknowledging there’s issues, restructuring your life to realize something’s off, and just knowing that you’re not alone? That’s huge.”

Dr. Desai said he still faces personal challenges but is in a much better place, doing well at work and at home. He talks to a therapist, is taking medication, and has developed better coping mechanisms. He is spending more time with his family, detaching for a few hours from work-related emails, learning to draw boundaries and say no, and trying to be more present and “intentional” in connecting with colleagues and patients.

“It’s okay to not be okay,” said Dr. Desai. “It’s okay to be vulnerable and acknowledge when we can’t do more.”

Are you in a crisis? Call or text 988 or text TALK to 741741. For immediate support for healthcare professionals, as well as resources for institutions and organizations, visit: afsp.org/suicide-prevention-for-healthcare-professionals/#facts-about-mental-health-and-suicide.

A version of this article appeared on Medscape.com.

Dhaval Desai, MD, was teaching his 4-year-old to ride a bike after another exhausting shift at the hospital during the summer after the first COVID-19 surge. He was putting on a happy face and forcing out a “Yay!” he did not feel. The pandemic had taken its toll, and he just wanted to lie down and be alone. Realizing that he was “scraping to find joy” was when he knew something was wrong.

“I was giving, giving, giving at work a lot, and I had little left to give at home,” said Dr. Desai, director of hospital medicine at Emory Saint Joseph’s Hospital and an assistant professor of medicine at Emory University in Atlanta, Georgia.

At work, he worried about his wife managing two kids — including a newborn — during the pandemic. At home, he stressed about work and the crush of patients with COVID the hospital was grappling to handle. He was exhausted, resentful, and angry, and it was jeopardizing what mattered most to him: His home life.

“It was all colliding…I realized, OK, I’m struggling,” he said.

Dr. Desai is one of thousands of physicians across the United States who have experienced burnout and depression, exacerbated by the pandemic. After 4 years, the impact is still being felt. Medscape’s 2024 annual report on this issue found that burnout and depression among doctors — while encouragingly better than the prior year — remain higher than before COVID. For doctors caring for patients with long COVID, those suffering from the debilitating aftereffects of an infection, the sense of helplessness when recovery is elusive can also weigh heavily.

Overall, more female physicians reported feeling burned out and depressed. Experts attributed this gap to issues including fewer women in supportive leadership and mentoring roles, compensation disparities, fewer career advancement opportunities, and more responsibilities caring for children and elders.

Multiple international studies and reports have highlighted the surge in burnout experienced by physicians and healthcare workers globally during the pandemic. Even before COVID, studies found the suicide rate among male and female US physicians was higher than the general population and higher than any other profession, including the military. The risk among female physicians, in particular, was 250%-400% higher.

“That’s really, on average, one a day, and that’s really unacceptable. No one should die by suicide, but a physician who knows the risks and knows that, should never do that,” said Dr. Desai about suicides overall among doctors.

The story of Lorna Breen had rattled Dr. Desai. Dr. Breen was a Manhattan physician who died by suicide in April 2020 after grappling with the city’s devastating first wave and then contracting COVID-19 herself. While Dr. Desai did not have thoughts of suicide, he was facing his own battles. Those experiences and the stigma around mental health prompted him to write his book, Burning Out on the Covid Front Lines: A Doctor’s Memoir of Fatherhood, Race and Perseverance in the Pandemic, with the hope that it can help others like him.
 

Mental Health Stigma

But despite the body of research and growing awareness toward addressing mental health among physicians, almost four in 10 doctors are wary of revealing their personal struggles.

More than half of those surveyed in the Medscape Medical News report said they had not consulted a mental health professional before and would not do so going forward either. The fear of tarnishing their reputation or even losing their license keeps doctors silent. Advocates and groups like the Dr. Lorna Breen Heroes’ Foundation are pushing for hospitals and healthcare systems to remove and rephrase invasive and stigmatizing language around mental health in licensure, credentialing, or insurance applications.
 

Burnout Triggers: Systemic Problems, Social Tensions

Burnout can make a person feel “depleted and used up” and is characterized by extreme tiredness, low energy, frustration about work, emotional distance or numbness, and difficulty with concentration, responsibilities, or creativity. It can make an individual feel helpless, alone, defeated, cynical, and without purpose and can also cause physical symptoms such as headaches, loss of appetite, insomnia, and body aches. Unaddressed, it can lead to depression, anxiety, and a variety of physical health issues.

“We can still be highly functional and not okay,” said Dr. Desai.

For doctors, burnout often builds over time from large and small systemic problems and inefficiencies, multiplied by a dozen or more patients each day: Not enough time for documentation, complicated paperwork, navigating byzantine health and insurance systems, and hitting roadblocks. The administrative work, combined with an enormous patient load, and staffing and resource shortages create barriers to care and cuts into the amount of time they can spend providing actual care.

These existing problems worsened as patients with COVID overwhelmed hospitals and clinics. At the same time, healthcare workers worried about caring for the sick, getting infected themselves, or having multiple staff falling ill at once. As each surge came and went, backlash, hostility, abuse, and even violence toward healthcare workers also increased. The discrimination some medical staff were subjected to compounded the burnout.

“When we’re not getting the support we need as physicians and healthcare workers, that adds to burnout, and I saw that in my colleagues,” said Dr. Desai.
 

Impact of Burnout

At the Mount Sinai Center for Post-COVID Care in New York City, doctors grapple with feelings of helplessness in caring for patients with long COVID who show little sign of recovery. That emotional toll can also be difficult, said director Zijian Chen, MD, who helped launch the clinic in May 2020.

“Sometimes you’re faced with patients who you’re trying to do everything for, but they’re not just not getting better,” said Dr. Chen. “It’s really frustrating because we want everybody to get better. So, there’s that lack of fulfillment there that can cause a sense of burnout.”

While the worst outcomes and death rates initially brought on by acute infections have lessened, long COVID clinics exemplify some of the ongoing challenges within healthcare. Many operate with insufficient financial and staffing resources despite wait-lists and a steady flow of new and returning patients. Even with the demand, a number of these clinics have shuttered, leaving patients without access to much-needed medical help.

“There are clinicians who are burning out. That is definitely something that I’ve seen,” said Monica Verduzco-Gutierrez, MD, a professor and chair of the Department of Rehabilitation Medicine at the University of Texas Health Science Center in San Antonio, Texas.

“[It] takes a lot of resources for a successful long COVID clinic. A lot of special funding may be drying up and couple that with clinicians burning out, then they’re going to shut their doors.”

And it’s not just long COVID clinics. Data have shown an overall exodus in healthcare, especially during the pandemic. One study found burnout was one of the “most impactful” predictors of a physician’s intention to leave the profession during the pandemic. The loss of talent and skills during a major health crisis can put the entire system under stress, with patients ultimately suffering from poorer care.

“Healthcare system fragility and the chaos is far worse than it was before. We are continuing to be forced to do more with less,” said Dr. Desai.
 

Alleviating Burnout

While it is difficult to assess whether burnout from the pandemic is transient, experts say this is an opportunity for health institutions to learn from these experiences and implement policies and actions that can help reduce the mental health strain on staff. One study found that changes made by organizations had a bigger positive impact on reducing burnout than individual changes.

Advocates say more support staff, more work flexibility, and higher compensation would significantly ease the burden that drives burnout and depression.

In addition, half the physicians surveyed in the Medscape Medical News report felt their employers were not acknowledging how pervasive burnout is at their workplace. Having a trusted peer or leader set an example by sharing his or her own challenging experiences and saying it›s time to address these struggles can be an enormously validating step forward, said Dr. Desai. Acknowledging his own difficulties was not only a huge weight off his shoulders but also helped surpris colleagues who sought him out for counsel.

“I’m not suggesting everybody get on medication,” he said. “But talking to a therapist, acknowledging there’s issues, restructuring your life to realize something’s off, and just knowing that you’re not alone? That’s huge.”

Dr. Desai said he still faces personal challenges but is in a much better place, doing well at work and at home. He talks to a therapist, is taking medication, and has developed better coping mechanisms. He is spending more time with his family, detaching for a few hours from work-related emails, learning to draw boundaries and say no, and trying to be more present and “intentional” in connecting with colleagues and patients.

“It’s okay to not be okay,” said Dr. Desai. “It’s okay to be vulnerable and acknowledge when we can’t do more.”

Are you in a crisis? Call or text 988 or text TALK to 741741. For immediate support for healthcare professionals, as well as resources for institutions and organizations, visit: afsp.org/suicide-prevention-for-healthcare-professionals/#facts-about-mental-health-and-suicide.

A version of this article appeared on Medscape.com.