MDedge Neurology

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated depression symptoms are linked to an increased risk for severe chemotherapy toxicity in older adults with cancer. This risk is mitigated by geriatric assessment (GA)-driven interventions.

METHODOLOGY:

• Researchers conducted a secondary analysis of a randomized controlled trial to evaluate whether greater reductions in grade 3 chemotherapy-related toxicities occurred with geriatric assessment-driven interventions vs standard care.
• A total of 605 patients aged 65 years and older with any stage of solid malignancy were included, with 402 randomized to the intervention arm and 203 to the standard-of-care arm.
• Mental health was assessed using the Mental Health Inventory 13, and chemotherapy toxicity was graded by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
• Patients in the intervention arm received recommendations from a multidisciplinary team based on their baseline GA, while those in the standard-of-care arm received only the baseline assessment results.
• The study was conducted at City of Hope National Medical Center in Duarte, California, and patients were followed throughout treatment or for up to 6 months from starting chemotherapy.

TAKEAWAY:

• According to the authors, patients with depression had increased chemotherapy toxicity in the standard-of-care arm (70.7% vs 54.3%; P = .02) but not in the GA-driven intervention arm (54.3% vs 48.5%; P = .27).
• The association between depression and chemotherapy toxicity was also seen after adjustment for the Cancer and Aging Research Group toxicity score (odds ratio, [OR], 1.98; 95% CI, 1.07-3.65) and for demographic, disease, and treatment factors (OR, 2.00; 95% CI, 1.03-3.85).
• No significant association was found between anxiety and chemotherapy toxicity in either the standard-of-care arm (univariate OR, 1.07; 95% CI, 0.61-1.88) or the GA-driven intervention arm (univariate OR, 1.15; 95% CI, 0.78-1.71).
• The authors stated that depression was associated with increased odds of hematologic-only toxicities (OR, 2.50; 95% CI, 1.13-5.56) in the standard-of-care arm.
• An analysis of a small subgroup found associations between elevated anxiety symptoms and increased risk for hematologic and nonhematologic chemotherapy toxicities.

IN PRACTICE:

“The current study showed that elevated depression symptoms are associated with increased risk of severe chemotherapy toxicities in older adults with cancer. This risk was mitigated in those in the GA intervention arm, which suggests that addressing elevated depression symptoms may lower the risk of toxicities,” the authors wrote. “Overall, elevated anxiety symptoms were not associated with risk for severe chemotherapy toxicity.”

SOURCE:

Reena V. Jayani, MD, MSCI, of Vanderbilt University Medical Center in Nashville, Tennessee, was the first and corresponding author for this paper. This study was published online August 4, 2024, in Cancer. 

LIMITATIONS:

The thresholds for depression and anxiety used in the Mental Health Inventory 13 were based on an English-speaking population, which may not be fully applicable to Chinese- and Spanish-speaking patients included in the study. Depression and anxiety were not evaluated by a mental health professional or with a structured interview to assess formal diagnostic criteria. Psychiatric medication used at the time of baseline GA was not included in the analysis. The study is a secondary analysis of a randomized controlled trial, and it is not known which components of the interventions affected mental health.

DISCLOSURES:

This research project was supported by the UniHealth Foundation, the City of Hope Center for Cancer and Aging, and the National Institutes of Health. One coauthor disclosed receiving institutional research funding from AstraZeneca and Brooklyn ImmunoTherapeutics and consulting for multiple pharmaceutical companies, including AbbVie, Adagene, and Bayer HealthCare Pharmaceuticals. William Dale, MD, PhD, of City of Hope National Medical Center, served as senior author and a principal investigator. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Jeffrey E. Janis, MD, is on a mission. The professor of plastic surgery, surgery, neurosurgery, and neurology at The Ohio State University Wexner Medical Center, Columbus, Ohio, wants to convince neurologists of the safety and efficacy of nerve decompression surgery for treatment-resistant headache. However, many neurologists remain unconvinced.

“Headache surgery is a viable alternative for complex patients who have failed medical management and who could benefit from this treatment approach. There’s 24 years of evidence behind this surgical technique across hundreds of different studies with different study designs,” Dr. Janis said. 

Yet this treatment approach — surgery on peripheral nerves rather than the brain or spinal cord — hasn’t garnered much support from neurologists. A scan of the agenda of topics at the recently held 2024 annual meeting of the American Headache Society showed few if any studies or presentations on this topic. And neurologists this news organization spoke to said they believe the surgery is experimental and unproven.

Experts do agree drugs don’t work for all patients with migraines. Up to 30% of patients don’t respond to the “laundry list of medications” available to treat the condition, said Dr. Janis.

Many patients have also tried, and failed, alternative treatment approaches such as massage, acupuncture, craniosacral therapy, transdermal patches, electrical stimulation, cryoablation, neurostimulation, and radiofrequency ablation.

If nothing else works, is surgery for headaches the answer?
 

Long-Held Theory

The idea that pinched, irritated, or compressed peripheral nerves can trigger migraine attacks has been around for nearly 25 years. Studies suggest that in addition to migraine, nerve compression can lead to other headache conditions, including occipital neuralgia, supraorbital neuralgia , and post-traumatic headaches.

This has led to the development of surgical techniques to deactivate various compression trigger sites — what Dr. Janis calls “pinch points” — which could involve muscles, bone, fascia, blood vessels, or scar tissue from prior trauma or surgery.

The procedure is predominantly performed by plastic surgeons, but to a lesser degree by neurosurgeons and ear, nose, and throat specialists.

Target nerves in surgical interventions include those in the frontal region of the head above the eye, temporal region, neck region, and nasal region. Affected areas are usually identified either through patient self-reports or by using a nerve block agent such as lidocaine or Botox at specific points, Dr. Janis noted. If pain subsides after an injection, that location is marked as a target.

One of the barriers to referring complicated patients for surgery is that neurologists evaluating migraine treatments “speak a different language” than surgeons performing the procedure, said Dr. Janis.

Neurologists tend to focus on reduction in monthly migraine days (MMD), while surgeons typically use the Migraine Headache Index that incorporates the frequency, intensity, and duration of migraine attacks.

“Rather than try to convince somebody to speak a different language, we thought, why don’t we just learn their language so we can build bridges and take down barriers,” said Dr. Janis, coauthor of a systematic review and meta-analysis published online recently in Plastic and Reconstructive Surgery.

Investigators examined 19 studies in the review, including five randomized controlled trials (RCTs), published from January 2020 to September 2023, with a total of 1603 participants who were mostly female and ranged in age from 9 to 72 years. Study follow-ups extended from 6 to 38 months. All but three studies were carried out in the United States, and six different compression sites were addressed during surgery.

Investigators found that across studies and by a number of measures, migraine frequency and severity improved after surgery.

Monthly migraine days decreased by 36%-92% and the number of overall migraine attacks per month dropped 25%-87.5%. Patients also reported decreases in attack duration of 41%-75% and intensity of 28%-82% across studies.

“Even using the neurologist-standard language of monthly migraine days, this surgery works,” said Dr. Janis. “Now this is documented both in the surgical literature and the nonsurgical literature.”

The most common complications were ecchymosis, hair loss or thinning, itching, dryness, and rhinorrhea, all of which Dr. Janis described as “fairly minor.” Major complications such as intraoperative bleeding and wound dehiscence were rare, occurring in 1% or less of participants.
 

‘One And Done?’

These surgeries are usually done on an outpatient basis and generally offer long-term results, Dr. Janis said.

“The idea is one and done,” he said. “The literature around this type of surgery says that whatever type of effect you get at 1 year is likely to be permanent.”

The American Society of Plastic Surgeons agrees. A 2018 position paper developed by experts and commissioned by the society reports that the intervention is safe and effective for appropriate patients, based on a comprehensive literature search and review of a large body of peer-reviewed scientific evidence.

“There is substantial, extensively replicated clinical data that demonstrates a significant reduction in [migraine headache] symptoms and frequency (even complete elimination of headache pain) following trigger site surgery,” the authors noted.

Pamela Blake, MD, a neurologist, board-certified headache specialist, and medical director at the Headache Center of River Oaks, Houston, is a proponent of what she said can be “lifesaving” headache surgery.

“If a doctor told you that you can either treat this problem with medications that you’ll need to take for the rest of your life or you can have a surgical procedure as an outpatient that has extremely low risk and has, in my experience, a 75% chance of reducing or eliminating your pain, you probably would be interested in surgery,” she said.
 

Continued Skepticism

However, other neurologists and clinicians appear doubtful about this intervention, including Hans-Christoph Diener, MD, PhD, professor of neurology and director, Essen Headache Centre, University of Duisburg-Essen in Germany.

During a debate on the topic a decade ago at the International Headache Congress, Dr. Diener argued that, as migraine is a complex multigene-related disorder of the brain, it doesn’t make sense that surgery would affect the epigenetics of 22 different genes.

Recently, he said that his views have not changed.

The topic remains controversial, and some neurologists are uncomfortable even openly discussing the procedure. Two clinicians who previously commented on this article later asked not to be included.

One neurologist, who asked to remain anonymous, said that Dr. Janis’s review article is “merely a review collecting 19 studies over the previous 10-plus years.”

Other limitations cited by this neurologist are the lack of consistency in procedures among the various studies and the inclusion of only four RCTs, the most recent of which was published 8 years ago, suggesting “the study was probably done closer to 9 or 10 years ago,” the neurologist said.

Dr. Blake suggested some neurologists’ reluctance could be due to limited background on the procedure, which she said isn’t widely discussed at headache meetings and is covered mostly in plastic surgery journals, not neurology literature. Access to surgery is further limited by a lack of specialists who perform the procedure and inconsistent insurance coverage.

A closer collaboration between neurologists and surgeons who perform the procedure could benefit patients, Dr. Blake noted.

“The headache doctor’s role is to identify who’s a candidate for surgery, who meets the criteria for nerve compression, and then follow that patient postoperatively, managing their medications, although usually we get them off their medications,” she added.

From Dr. Janis’s perspective, things are starting to change.

“I’m definitely seeing a greater comfort level among neurologists who are understanding where this sits in the algorithm for treatment, especially for complicated patients,” he said.

Dr. Janis receives royalties from Thieme and Springer Publishing. Dr. Blake reported no relevant conflicts. Dr. Diener received research support from the German Research Council; serves on the editorial boards of Cephalalgia, Lancet Neurology, and Drugs; and has received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva, Weber & Weber, and WebMD.

A version of this article appeared on Medscape.com.

Jeffrey E. Janis, MD, is on a mission. The professor of plastic surgery, surgery, neurosurgery, and neurology at The Ohio State University Wexner Medical Center, Columbus, Ohio, wants to convince neurologists of the safety and efficacy of nerve decompression surgery for treatment-resistant headache. However, many neurologists remain unconvinced.

“Headache surgery is a viable alternative for complex patients who have failed medical management and who could benefit from this treatment approach. There’s 24 years of evidence behind this surgical technique across hundreds of different studies with different study designs,” Dr. Janis said. 

Yet this treatment approach — surgery on peripheral nerves rather than the brain or spinal cord — hasn’t garnered much support from neurologists. A scan of the agenda of topics at the recently held 2024 annual meeting of the American Headache Society showed few if any studies or presentations on this topic. And neurologists this news organization spoke to said they believe the surgery is experimental and unproven.

Experts do agree drugs don’t work for all patients with migraines. Up to 30% of patients don’t respond to the “laundry list of medications” available to treat the condition, said Dr. Janis.

Many patients have also tried, and failed, alternative treatment approaches such as massage, acupuncture, craniosacral therapy, transdermal patches, electrical stimulation, cryoablation, neurostimulation, and radiofrequency ablation.

If nothing else works, is surgery for headaches the answer?
 

Long-Held Theory

The idea that pinched, irritated, or compressed peripheral nerves can trigger migraine attacks has been around for nearly 25 years. Studies suggest that in addition to migraine, nerve compression can lead to other headache conditions, including occipital neuralgia, supraorbital neuralgia , and post-traumatic headaches.

This has led to the development of surgical techniques to deactivate various compression trigger sites — what Dr. Janis calls “pinch points” — which could involve muscles, bone, fascia, blood vessels, or scar tissue from prior trauma or surgery.

The procedure is predominantly performed by plastic surgeons, but to a lesser degree by neurosurgeons and ear, nose, and throat specialists.

Target nerves in surgical interventions include those in the frontal region of the head above the eye, temporal region, neck region, and nasal region. Affected areas are usually identified either through patient self-reports or by using a nerve block agent such as lidocaine or Botox at specific points, Dr. Janis noted. If pain subsides after an injection, that location is marked as a target.

One of the barriers to referring complicated patients for surgery is that neurologists evaluating migraine treatments “speak a different language” than surgeons performing the procedure, said Dr. Janis.

Neurologists tend to focus on reduction in monthly migraine days (MMD), while surgeons typically use the Migraine Headache Index that incorporates the frequency, intensity, and duration of migraine attacks.

“Rather than try to convince somebody to speak a different language, we thought, why don’t we just learn their language so we can build bridges and take down barriers,” said Dr. Janis, coauthor of a systematic review and meta-analysis published online recently in Plastic and Reconstructive Surgery.

Investigators examined 19 studies in the review, including five randomized controlled trials (RCTs), published from January 2020 to September 2023, with a total of 1603 participants who were mostly female and ranged in age from 9 to 72 years. Study follow-ups extended from 6 to 38 months. All but three studies were carried out in the United States, and six different compression sites were addressed during surgery.

Investigators found that across studies and by a number of measures, migraine frequency and severity improved after surgery.

Monthly migraine days decreased by 36%-92% and the number of overall migraine attacks per month dropped 25%-87.5%. Patients also reported decreases in attack duration of 41%-75% and intensity of 28%-82% across studies.

“Even using the neurologist-standard language of monthly migraine days, this surgery works,” said Dr. Janis. “Now this is documented both in the surgical literature and the nonsurgical literature.”

The most common complications were ecchymosis, hair loss or thinning, itching, dryness, and rhinorrhea, all of which Dr. Janis described as “fairly minor.” Major complications such as intraoperative bleeding and wound dehiscence were rare, occurring in 1% or less of participants.
 

‘One And Done?’

These surgeries are usually done on an outpatient basis and generally offer long-term results, Dr. Janis said.

“The idea is one and done,” he said. “The literature around this type of surgery says that whatever type of effect you get at 1 year is likely to be permanent.”

The American Society of Plastic Surgeons agrees. A 2018 position paper developed by experts and commissioned by the society reports that the intervention is safe and effective for appropriate patients, based on a comprehensive literature search and review of a large body of peer-reviewed scientific evidence.

“There is substantial, extensively replicated clinical data that demonstrates a significant reduction in [migraine headache] symptoms and frequency (even complete elimination of headache pain) following trigger site surgery,” the authors noted.

Pamela Blake, MD, a neurologist, board-certified headache specialist, and medical director at the Headache Center of River Oaks, Houston, is a proponent of what she said can be “lifesaving” headache surgery.

“If a doctor told you that you can either treat this problem with medications that you’ll need to take for the rest of your life or you can have a surgical procedure as an outpatient that has extremely low risk and has, in my experience, a 75% chance of reducing or eliminating your pain, you probably would be interested in surgery,” she said.
 

Continued Skepticism

However, other neurologists and clinicians appear doubtful about this intervention, including Hans-Christoph Diener, MD, PhD, professor of neurology and director, Essen Headache Centre, University of Duisburg-Essen in Germany.

During a debate on the topic a decade ago at the International Headache Congress, Dr. Diener argued that, as migraine is a complex multigene-related disorder of the brain, it doesn’t make sense that surgery would affect the epigenetics of 22 different genes.

Recently, he said that his views have not changed.

The topic remains controversial, and some neurologists are uncomfortable even openly discussing the procedure. Two clinicians who previously commented on this article later asked not to be included.

One neurologist, who asked to remain anonymous, said that Dr. Janis’s review article is “merely a review collecting 19 studies over the previous 10-plus years.”

Other limitations cited by this neurologist are the lack of consistency in procedures among the various studies and the inclusion of only four RCTs, the most recent of which was published 8 years ago, suggesting “the study was probably done closer to 9 or 10 years ago,” the neurologist said.

Dr. Blake suggested some neurologists’ reluctance could be due to limited background on the procedure, which she said isn’t widely discussed at headache meetings and is covered mostly in plastic surgery journals, not neurology literature. Access to surgery is further limited by a lack of specialists who perform the procedure and inconsistent insurance coverage.

A closer collaboration between neurologists and surgeons who perform the procedure could benefit patients, Dr. Blake noted.

“The headache doctor’s role is to identify who’s a candidate for surgery, who meets the criteria for nerve compression, and then follow that patient postoperatively, managing their medications, although usually we get them off their medications,” she added.

From Dr. Janis’s perspective, things are starting to change.

“I’m definitely seeing a greater comfort level among neurologists who are understanding where this sits in the algorithm for treatment, especially for complicated patients,” he said.

Dr. Janis receives royalties from Thieme and Springer Publishing. Dr. Blake reported no relevant conflicts. Dr. Diener received research support from the German Research Council; serves on the editorial boards of Cephalalgia, Lancet Neurology, and Drugs; and has received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva, Weber & Weber, and WebMD.

A version of this article appeared on Medscape.com.

Jeffrey E. Janis, MD, is on a mission. The professor of plastic surgery, surgery, neurosurgery, and neurology at The Ohio State University Wexner Medical Center, Columbus, Ohio, wants to convince neurologists of the safety and efficacy of nerve decompression surgery for treatment-resistant headache. However, many neurologists remain unconvinced.

“Headache surgery is a viable alternative for complex patients who have failed medical management and who could benefit from this treatment approach. There’s 24 years of evidence behind this surgical technique across hundreds of different studies with different study designs,” Dr. Janis said. 

Yet this treatment approach — surgery on peripheral nerves rather than the brain or spinal cord — hasn’t garnered much support from neurologists. A scan of the agenda of topics at the recently held 2024 annual meeting of the American Headache Society showed few if any studies or presentations on this topic. And neurologists this news organization spoke to said they believe the surgery is experimental and unproven.

Experts do agree drugs don’t work for all patients with migraines. Up to 30% of patients don’t respond to the “laundry list of medications” available to treat the condition, said Dr. Janis.

Many patients have also tried, and failed, alternative treatment approaches such as massage, acupuncture, craniosacral therapy, transdermal patches, electrical stimulation, cryoablation, neurostimulation, and radiofrequency ablation.

If nothing else works, is surgery for headaches the answer?
 

Long-Held Theory

The idea that pinched, irritated, or compressed peripheral nerves can trigger migraine attacks has been around for nearly 25 years. Studies suggest that in addition to migraine, nerve compression can lead to other headache conditions, including occipital neuralgia, supraorbital neuralgia , and post-traumatic headaches.

This has led to the development of surgical techniques to deactivate various compression trigger sites — what Dr. Janis calls “pinch points” — which could involve muscles, bone, fascia, blood vessels, or scar tissue from prior trauma or surgery.

The procedure is predominantly performed by plastic surgeons, but to a lesser degree by neurosurgeons and ear, nose, and throat specialists.

Target nerves in surgical interventions include those in the frontal region of the head above the eye, temporal region, neck region, and nasal region. Affected areas are usually identified either through patient self-reports or by using a nerve block agent such as lidocaine or Botox at specific points, Dr. Janis noted. If pain subsides after an injection, that location is marked as a target.

One of the barriers to referring complicated patients for surgery is that neurologists evaluating migraine treatments “speak a different language” than surgeons performing the procedure, said Dr. Janis.

Neurologists tend to focus on reduction in monthly migraine days (MMD), while surgeons typically use the Migraine Headache Index that incorporates the frequency, intensity, and duration of migraine attacks.

“Rather than try to convince somebody to speak a different language, we thought, why don’t we just learn their language so we can build bridges and take down barriers,” said Dr. Janis, coauthor of a systematic review and meta-analysis published online recently in Plastic and Reconstructive Surgery.

Investigators examined 19 studies in the review, including five randomized controlled trials (RCTs), published from January 2020 to September 2023, with a total of 1603 participants who were mostly female and ranged in age from 9 to 72 years. Study follow-ups extended from 6 to 38 months. All but three studies were carried out in the United States, and six different compression sites were addressed during surgery.

Investigators found that across studies and by a number of measures, migraine frequency and severity improved after surgery.

Monthly migraine days decreased by 36%-92% and the number of overall migraine attacks per month dropped 25%-87.5%. Patients also reported decreases in attack duration of 41%-75% and intensity of 28%-82% across studies.

“Even using the neurologist-standard language of monthly migraine days, this surgery works,” said Dr. Janis. “Now this is documented both in the surgical literature and the nonsurgical literature.”

The most common complications were ecchymosis, hair loss or thinning, itching, dryness, and rhinorrhea, all of which Dr. Janis described as “fairly minor.” Major complications such as intraoperative bleeding and wound dehiscence were rare, occurring in 1% or less of participants.
 

‘One And Done?’

These surgeries are usually done on an outpatient basis and generally offer long-term results, Dr. Janis said.

“The idea is one and done,” he said. “The literature around this type of surgery says that whatever type of effect you get at 1 year is likely to be permanent.”

The American Society of Plastic Surgeons agrees. A 2018 position paper developed by experts and commissioned by the society reports that the intervention is safe and effective for appropriate patients, based on a comprehensive literature search and review of a large body of peer-reviewed scientific evidence.

“There is substantial, extensively replicated clinical data that demonstrates a significant reduction in [migraine headache] symptoms and frequency (even complete elimination of headache pain) following trigger site surgery,” the authors noted.

Pamela Blake, MD, a neurologist, board-certified headache specialist, and medical director at the Headache Center of River Oaks, Houston, is a proponent of what she said can be “lifesaving” headache surgery.

“If a doctor told you that you can either treat this problem with medications that you’ll need to take for the rest of your life or you can have a surgical procedure as an outpatient that has extremely low risk and has, in my experience, a 75% chance of reducing or eliminating your pain, you probably would be interested in surgery,” she said.
 

Continued Skepticism

However, other neurologists and clinicians appear doubtful about this intervention, including Hans-Christoph Diener, MD, PhD, professor of neurology and director, Essen Headache Centre, University of Duisburg-Essen in Germany.

During a debate on the topic a decade ago at the International Headache Congress, Dr. Diener argued that, as migraine is a complex multigene-related disorder of the brain, it doesn’t make sense that surgery would affect the epigenetics of 22 different genes.

Recently, he said that his views have not changed.

The topic remains controversial, and some neurologists are uncomfortable even openly discussing the procedure. Two clinicians who previously commented on this article later asked not to be included.

One neurologist, who asked to remain anonymous, said that Dr. Janis’s review article is “merely a review collecting 19 studies over the previous 10-plus years.”

Other limitations cited by this neurologist are the lack of consistency in procedures among the various studies and the inclusion of only four RCTs, the most recent of which was published 8 years ago, suggesting “the study was probably done closer to 9 or 10 years ago,” the neurologist said.

Dr. Blake suggested some neurologists’ reluctance could be due to limited background on the procedure, which she said isn’t widely discussed at headache meetings and is covered mostly in plastic surgery journals, not neurology literature. Access to surgery is further limited by a lack of specialists who perform the procedure and inconsistent insurance coverage.

A closer collaboration between neurologists and surgeons who perform the procedure could benefit patients, Dr. Blake noted.

“The headache doctor’s role is to identify who’s a candidate for surgery, who meets the criteria for nerve compression, and then follow that patient postoperatively, managing their medications, although usually we get them off their medications,” she added.

From Dr. Janis’s perspective, things are starting to change.

“I’m definitely seeing a greater comfort level among neurologists who are understanding where this sits in the algorithm for treatment, especially for complicated patients,” he said.

Dr. Janis receives royalties from Thieme and Springer Publishing. Dr. Blake reported no relevant conflicts. Dr. Diener received research support from the German Research Council; serves on the editorial boards of Cephalalgia, Lancet Neurology, and Drugs; and has received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva, Weber & Weber, and WebMD.

A version of this article appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved vorasidenib (Voranigo, Servier) for the treatment of certain isocitrate dehydrogenase (IDH)–mutant diffuse gliomas, marking the first approval of a targeted therapy for these types of brain tumors.

Specifically, the oral targeted inhibitor of IDH1 and IDH2 was approved for use after surgery in adults and children aged 12 years or older who have grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. According to the FDA, surgery includes biopsy, subtotal resection, or gross total resection. 

Mutations in IDH1 are present in around 80% of grade 2 gliomas, whereas IDH2 mutations are more infrequent, occurring in about 4%. 

Prior to the approval, which was based on progression-free survival (PFS) and safety findings from the pivotal phase 3 INDIGO trial, patients with this type of glioma had limited treatment options, said a Servier spokesperson.

The approval of vorasidenib marks “one of the biggest advances in low-grade glioma in more than two decades” and “will empower patients to take active control of their disease with a once-daily pill,” according to the spokesperson.

In the INDIGO trial, 331 patients were randomly assigned to receive 40 mg of vorasidenib once daily (n = 168) or placebo (n = 163). At a median follow-up of 14.2 months, the median PFS was more than twice as long among those who received vorasidenib vs placebo: 27.7 months vs 11.1 months, respectively (hazard ratio [HR] for disease progression or death, 0.39). The time to next intervention was also significantly longer with vorasidenib vs placebo (median not reached vs 17.8 months, respectively; HR, 0.26).

The 61% reduction in the risk for tumor progression or death observed in the trial represents “a significant sign of efficacy that has the potential to change the landscape in this disease,” first author Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York City, told this news organization in 2023, when presenting the findings at the 2023 American Society of Clinical Oncology conference. These findings were simultaneously published in The New England Journal of Medicine.

Glenn Lesser, MD, a discussant at the 2023 meeting, commented on the “striking” findings. The results are “statistically highly significant, and more importantly, they’re clinically very, very significant,” said Dr. Lesser, from Wake Forest Baptist Health in Winston-Salem, North Carolina.

Vorasidenib can also potentially delay the use of toxic chemotherapies and radiation for many years in patients with these tumors, Dr. Lesser added.

Adverse events of grade 3 or higher occurred in 22.8% of those who received vorasidenib and in 13.5% of those in the placebo group. Increased alanine aminotransferase levels of grade 3 or higher occurred in 9.6 vs 0% of patients in the groups, respectively.

The most common adverse reactions with vorasidenib, affecting at least 15% of treated patients, include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as decreased neutrophils. 

The recommended dose of vorasidenib for adults is 40 mg given orally once daily until disease progression or unacceptable toxicity. In children aged 12 or older, the recommended dose is 40 mg given orally once daily for those weighing ≥ 40 kg, and 20 mg given orally once daily for those weighing < 40 kg.

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

The US Food and Drug Administration (FDA) has approved vorasidenib (Voranigo, Servier) for the treatment of certain isocitrate dehydrogenase (IDH)–mutant diffuse gliomas, marking the first approval of a targeted therapy for these types of brain tumors.

Specifically, the oral targeted inhibitor of IDH1 and IDH2 was approved for use after surgery in adults and children aged 12 years or older who have grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. According to the FDA, surgery includes biopsy, subtotal resection, or gross total resection. 

Mutations in IDH1 are present in around 80% of grade 2 gliomas, whereas IDH2 mutations are more infrequent, occurring in about 4%. 

Prior to the approval, which was based on progression-free survival (PFS) and safety findings from the pivotal phase 3 INDIGO trial, patients with this type of glioma had limited treatment options, said a Servier spokesperson.

The approval of vorasidenib marks “one of the biggest advances in low-grade glioma in more than two decades” and “will empower patients to take active control of their disease with a once-daily pill,” according to the spokesperson.

In the INDIGO trial, 331 patients were randomly assigned to receive 40 mg of vorasidenib once daily (n = 168) or placebo (n = 163). At a median follow-up of 14.2 months, the median PFS was more than twice as long among those who received vorasidenib vs placebo: 27.7 months vs 11.1 months, respectively (hazard ratio [HR] for disease progression or death, 0.39). The time to next intervention was also significantly longer with vorasidenib vs placebo (median not reached vs 17.8 months, respectively; HR, 0.26).

The 61% reduction in the risk for tumor progression or death observed in the trial represents “a significant sign of efficacy that has the potential to change the landscape in this disease,” first author Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York City, told this news organization in 2023, when presenting the findings at the 2023 American Society of Clinical Oncology conference. These findings were simultaneously published in The New England Journal of Medicine.

Glenn Lesser, MD, a discussant at the 2023 meeting, commented on the “striking” findings. The results are “statistically highly significant, and more importantly, they’re clinically very, very significant,” said Dr. Lesser, from Wake Forest Baptist Health in Winston-Salem, North Carolina.

Vorasidenib can also potentially delay the use of toxic chemotherapies and radiation for many years in patients with these tumors, Dr. Lesser added.

Adverse events of grade 3 or higher occurred in 22.8% of those who received vorasidenib and in 13.5% of those in the placebo group. Increased alanine aminotransferase levels of grade 3 or higher occurred in 9.6 vs 0% of patients in the groups, respectively.

The most common adverse reactions with vorasidenib, affecting at least 15% of treated patients, include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as decreased neutrophils. 

The recommended dose of vorasidenib for adults is 40 mg given orally once daily until disease progression or unacceptable toxicity. In children aged 12 or older, the recommended dose is 40 mg given orally once daily for those weighing ≥ 40 kg, and 20 mg given orally once daily for those weighing < 40 kg.

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

The US Food and Drug Administration (FDA) has approved vorasidenib (Voranigo, Servier) for the treatment of certain isocitrate dehydrogenase (IDH)–mutant diffuse gliomas, marking the first approval of a targeted therapy for these types of brain tumors.

Specifically, the oral targeted inhibitor of IDH1 and IDH2 was approved for use after surgery in adults and children aged 12 years or older who have grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation. According to the FDA, surgery includes biopsy, subtotal resection, or gross total resection. 

Mutations in IDH1 are present in around 80% of grade 2 gliomas, whereas IDH2 mutations are more infrequent, occurring in about 4%. 

Prior to the approval, which was based on progression-free survival (PFS) and safety findings from the pivotal phase 3 INDIGO trial, patients with this type of glioma had limited treatment options, said a Servier spokesperson.

The approval of vorasidenib marks “one of the biggest advances in low-grade glioma in more than two decades” and “will empower patients to take active control of their disease with a once-daily pill,” according to the spokesperson.

In the INDIGO trial, 331 patients were randomly assigned to receive 40 mg of vorasidenib once daily (n = 168) or placebo (n = 163). At a median follow-up of 14.2 months, the median PFS was more than twice as long among those who received vorasidenib vs placebo: 27.7 months vs 11.1 months, respectively (hazard ratio [HR] for disease progression or death, 0.39). The time to next intervention was also significantly longer with vorasidenib vs placebo (median not reached vs 17.8 months, respectively; HR, 0.26).

The 61% reduction in the risk for tumor progression or death observed in the trial represents “a significant sign of efficacy that has the potential to change the landscape in this disease,” first author Ingo K. Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center, New York City, told this news organization in 2023, when presenting the findings at the 2023 American Society of Clinical Oncology conference. These findings were simultaneously published in The New England Journal of Medicine.

Glenn Lesser, MD, a discussant at the 2023 meeting, commented on the “striking” findings. The results are “statistically highly significant, and more importantly, they’re clinically very, very significant,” said Dr. Lesser, from Wake Forest Baptist Health in Winston-Salem, North Carolina.

Vorasidenib can also potentially delay the use of toxic chemotherapies and radiation for many years in patients with these tumors, Dr. Lesser added.

Adverse events of grade 3 or higher occurred in 22.8% of those who received vorasidenib and in 13.5% of those in the placebo group. Increased alanine aminotransferase levels of grade 3 or higher occurred in 9.6 vs 0% of patients in the groups, respectively.

The most common adverse reactions with vorasidenib, affecting at least 15% of treated patients, include fatigue, headache, COVID-19, musculoskeletal pain, diarrhea, nausea, and seizure. The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase as well as decreased neutrophils. 

The recommended dose of vorasidenib for adults is 40 mg given orally once daily until disease progression or unacceptable toxicity. In children aged 12 or older, the recommended dose is 40 mg given orally once daily for those weighing ≥ 40 kg, and 20 mg given orally once daily for those weighing < 40 kg.

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

For most of my formative years in medicine it was taken as gospel that 1-2 drinks/day, particularly red wine, was good for you.

Today though, the pendulum has swung the other way (granted, that could change in a year).

Recent re-analysis of the data now suggests there’s no benefit to any amount of alcohol. Zero. Zip. Nada.

This certainly isn’t the first time in medicine this has happened. It’s amazing how many studies end up getting re-analyzed, and re-re-analyzed, years later, with different conclusions reached.

It makes you wonder how these things happen. Possible explanations include flawed methodologies that either weren’t recognized at the time, confirmation bias, a rush to publish, and, rarely, outright fraud.

All of them, except for the last, are understandable. We all make mistakes. We’re all susceptible to the same statistical and psychological biases. Isn’t that part of the reason we do the peer-review process, so more than one pair of eyes can look for errors?

So, basically, no amount of alcohol is good for you.

Do I really think this is going to change anything? Hell no.

A huge amount of our culture revolves around alcohol. I’m not much of a drinker, but have no desire to give up my 2-3 beers per month, either. Just shopping in the store you see T-shirts, kitchen towels, gift bags, etc., that say things like “wine is just fruit salad” or “1 tequila, 2, tequila, 3 tequila, floor.”

The archaeological record suggests we began making alcoholic beverages 13,000 years ago. That’s a long time, and a pretty hard cultural habit to break. For comparison, tobacco has only been used for 3000 years.

In one of our strangest moments, America launched a 13-year experiment in prohibition, which failed miserably. Think about that. One hundred years ago, in 1924, you couldn’t legally buy alcohol anywhere in the United States. You had to break the law to get a drink, which most people did. Even then it was dangerous —in order to keep industrial ethanol from being sold to the public it was denatured with various toxins. As a result several thousand Americans died from their routine nightcap — with the government’s blessing.

Basically, alcohol isn’t going away. Not now, probably not ever.

There may be some out there who will alter their drinking habits based on the study, but I doubt it. I just don’t see too many people having a glass solely for the same reason they might take Lipitor or a multivitamin.

But I have no issue with correcting the original data. In medicine, and life in general, finding out what works is just as important as learning what doesn’t.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

For most of my formative years in medicine it was taken as gospel that 1-2 drinks/day, particularly red wine, was good for you.

Today though, the pendulum has swung the other way (granted, that could change in a year).

Recent re-analysis of the data now suggests there’s no benefit to any amount of alcohol. Zero. Zip. Nada.

This certainly isn’t the first time in medicine this has happened. It’s amazing how many studies end up getting re-analyzed, and re-re-analyzed, years later, with different conclusions reached.

It makes you wonder how these things happen. Possible explanations include flawed methodologies that either weren’t recognized at the time, confirmation bias, a rush to publish, and, rarely, outright fraud.

All of them, except for the last, are understandable. We all make mistakes. We’re all susceptible to the same statistical and psychological biases. Isn’t that part of the reason we do the peer-review process, so more than one pair of eyes can look for errors?

So, basically, no amount of alcohol is good for you.

Do I really think this is going to change anything? Hell no.

A huge amount of our culture revolves around alcohol. I’m not much of a drinker, but have no desire to give up my 2-3 beers per month, either. Just shopping in the store you see T-shirts, kitchen towels, gift bags, etc., that say things like “wine is just fruit salad” or “1 tequila, 2, tequila, 3 tequila, floor.”

The archaeological record suggests we began making alcoholic beverages 13,000 years ago. That’s a long time, and a pretty hard cultural habit to break. For comparison, tobacco has only been used for 3000 years.

In one of our strangest moments, America launched a 13-year experiment in prohibition, which failed miserably. Think about that. One hundred years ago, in 1924, you couldn’t legally buy alcohol anywhere in the United States. You had to break the law to get a drink, which most people did. Even then it was dangerous —in order to keep industrial ethanol from being sold to the public it was denatured with various toxins. As a result several thousand Americans died from their routine nightcap — with the government’s blessing.

Basically, alcohol isn’t going away. Not now, probably not ever.

There may be some out there who will alter their drinking habits based on the study, but I doubt it. I just don’t see too many people having a glass solely for the same reason they might take Lipitor or a multivitamin.

But I have no issue with correcting the original data. In medicine, and life in general, finding out what works is just as important as learning what doesn’t.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

For most of my formative years in medicine it was taken as gospel that 1-2 drinks/day, particularly red wine, was good for you.

Today though, the pendulum has swung the other way (granted, that could change in a year).

Recent re-analysis of the data now suggests there’s no benefit to any amount of alcohol. Zero. Zip. Nada.

This certainly isn’t the first time in medicine this has happened. It’s amazing how many studies end up getting re-analyzed, and re-re-analyzed, years later, with different conclusions reached.

It makes you wonder how these things happen. Possible explanations include flawed methodologies that either weren’t recognized at the time, confirmation bias, a rush to publish, and, rarely, outright fraud.

All of them, except for the last, are understandable. We all make mistakes. We’re all susceptible to the same statistical and psychological biases. Isn’t that part of the reason we do the peer-review process, so more than one pair of eyes can look for errors?

So, basically, no amount of alcohol is good for you.

Do I really think this is going to change anything? Hell no.

A huge amount of our culture revolves around alcohol. I’m not much of a drinker, but have no desire to give up my 2-3 beers per month, either. Just shopping in the store you see T-shirts, kitchen towels, gift bags, etc., that say things like “wine is just fruit salad” or “1 tequila, 2, tequila, 3 tequila, floor.”

The archaeological record suggests we began making alcoholic beverages 13,000 years ago. That’s a long time, and a pretty hard cultural habit to break. For comparison, tobacco has only been used for 3000 years.

In one of our strangest moments, America launched a 13-year experiment in prohibition, which failed miserably. Think about that. One hundred years ago, in 1924, you couldn’t legally buy alcohol anywhere in the United States. You had to break the law to get a drink, which most people did. Even then it was dangerous —in order to keep industrial ethanol from being sold to the public it was denatured with various toxins. As a result several thousand Americans died from their routine nightcap — with the government’s blessing.

Basically, alcohol isn’t going away. Not now, probably not ever.

There may be some out there who will alter their drinking habits based on the study, but I doubt it. I just don’t see too many people having a glass solely for the same reason they might take Lipitor or a multivitamin.

But I have no issue with correcting the original data. In medicine, and life in general, finding out what works is just as important as learning what doesn’t.
 

Dr. Block has a solo neurology practice in Scottsdale, Arizona.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

The ability of advanced diffusion MRI (dMRI) techniques to detect microstructural neurological changes in military patients with remote mild traumatic brain injury (mTBI) supports wider adoption of these techniques, according to authors of a recent study. In particular, they said, using neurite orientation dispersion and density imaging (NODDI) to monitor long-term mTBI impact on brain regions related to cognitive and emotional processing can help clinicians assess recovery, predict progression, and optimize treatment.

“Currently,” said co-senior study author Ping-Hong Yeh, PhD, “there is a lack of minimally invasive, quantitative diagnostic biomarkers for monitoring progression or recovery after mild TBI. However, mild TBI can be quite disabling, with many patients reporting symptoms months or even years after injury. This is the most difficult part to diagnose.” Dr. Yeh is a researcher at the National Intrepid Center of Excellence (NICoE) at Walter Reed National Military Medical Center, Bethesda, Maryland.

The NICoE, a Department of Defense organization and the senior member of Defense Intrepid Network for Traumatic Brain Injury and Brain Health, is among several centers charged with improving support for injured service members’ recovery, rehabilitation, and reintegration into their communities. The overarching goal, said Dr. Yeh, is to enable community neurologists to refer service members and veterans to these centers for treatment and advanced imaging when needed.
 

Invisible Wounds

Limitations of conventional MRI and CT make it tough to discern which patients with mTBI will return to baseline functioning, and which will develop long-term complications. Addressing the silent or invisible wounds of mTBI will require improved diagnostic, prognostic, and therapeutic tools, he said.

For their study, published in JAMA Network Open, Dr. Yeh and colleagues compared diffusion tensor imaging (DTI) and NODDI data from 65 male service members with remote (more than 2 years old) mTBI against scans of 33 noninjured controls matched for age, sex, and active-duty status.

“Although DTI is very sensitive in detecting microstructural changes in mild TBI,” he said, “it is not specific to the underlying pathophysiological changes.”

Conversely, NODDI uses biophysical modeling of intracellular diffusion, extracellular diffusion, and free water to help physicians to understand subtle pathophysiological changes with greater sensitivity and specificity than does DTI. “This will allow us to correlate symptoms with brain structural changes, making the invisible wound visible.”

In the study, the greatest differences between injured and control patients appeared in the following NODDI metrics (P <.001 in all analyses):

• Intracellular volume fraction (ICVF) of the right corticospinal tract (CST)
• Orientation dispersion index (ODI) of the left posterior thalamic radiation (PTR)
• ODI of the left uncinate fasciculus (UNC)

Regarding patient-reported neurobehavioral symptoms, Neurobehavioral Symptom Inventory cognitive subscores were associated with fractional anisotropy of the left UNC. In addition, PTSD Checklist–Civilian version total scores and avoidance subscores corresponded, respectively, with isotropic volume fraction (ISOVF) of the genu of corpus callosum and with ODI of the left fornix and stria terminalis.
 

Next Steps

Presently, Dr. Yeh said, conventional MRI and CT usually cannot differentiate between axonal injury, axonal inflammation (which develops during the chronic phase of mTBI), and demyelination. “But newer biophysical modeling, such as NODDI, will allow us to tell the difference.” Along with providing prognostic information, he said, such technology can guide appropriate treatment, such as anti-inflammatory agents for chronic inflammation.

Most community neurologists refer patients with persistent mTBI symptoms in the absence of red flags using CT and conventional MRI for advanced neuroimaging, said Dr. Yeh. But because few community neurologists are familiar with NODDI, he said, broadening its reach will require educating these providers. Additional steps that Dr. Yeh said could occur over the next decade or more include boosting advanced dMRI sensitivity levels through improved hardware, software, and diagnostic tools.

“We need to make these techniques clinically feasible,” he added. Currently, protocols that allow advanced dMRI scans in about 10 minutes can be achievable.

The investments required to implement advanced dMRI techniques will be substantial. A state-of-the-art 3T MRI scanner that can support NODDI and DTI can easily cost $1 million, said Dr. Yeh. Factor in additional equipment options and construction costs, he added, and the total price tag can easily exceed $2 million. But rather than replacing all existing MRI systems, said Dr. Yeh, AI one day may help translate high-gradient capability even to widely used lower-field MRI scanners operating at 0.5T.

Streamlining systems that incorporate disparate scanners with different acquisition parameters will require standardized data acquisition and sharing parameters. Along with helping to evaluate new techniques as they become available, data harmonization and sharing can facilitate a shift from research comparisons between large groups to comparing a single patient against many others — a move that Dr. Yeh said must occur for advanced dMRI techniques to achieve clinical relevance.

In addition, experts will need to revise clinical guidelines for use of new technologies as their availability grows. “Improper use of these techniques will not only increase health costs, but also probably result in adverse health results.” Such guidelines could be very useful in evaluating the suitability and quality of referrals for diagnostic images, Dr. Yeh said.

Dr. Yeh reports no relevant financial interests. The project was partially funded by the US Army Medical Research and Materiel Command.

Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government’s complaint “serves as a warning” to healthcare providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to this news organization, Erlanger denied the allegations and said it would “vigorously” defend the lawsuit. 

“Erlanger paid physicians based on amounts that outside experts advised was fair market value,” Erlanger officials said in the statement. “Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims.”

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

“There is a tendency by physicians when contracting ... to rely on [hospitals’] perceived compliance and legal expertise,” Mr. Sarraille told this news organization. “This case illustrates the risks in doing so. Sometimes bigger doesn’t translate into more sophisticated or more effective from a compliance perspective.” 
 

Stark Law Prohibits Kickbacks

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

“HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase healthcare costs, and erode public trust in the healthcare system,” Ms. Miles said in a statement. 
 

Suit: Health System’s Money Woes Led to Illegal Arrangements

Erlanger’s financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government’s complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger’s agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government’s lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger’s physicians were expected to treat patients at Erlanger’s hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger’s CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.

In addition, Erlanger ignored patient safety concerns about some of its high revenue-generating physicians, the government claims. 

For instance, Erlanger received multiple complaints that a cardiothoracic surgeon was misusing an expensive form of life support in which pumps and oxygenators take over heart and lung function. Overuse of the equipment prolonged patients’ hospital stays and increased the hospital fees generated by the surgeon, according to the complaint. Staff also raised concerns about the cardiothoracic surgeon’s patient outcomes. 

But Erlanger disregarded the concerns and in 2018, increased the cardiothoracic surgeon’s retention bonus from $100,000 to $250,000, the suit alleges. A year later, the health system increased his base salary from $1,070,000 to $1,195,000.

Health care compensation and billing consultants alerted Erlanger that it was overpaying salaries and handing out bonuses based on measures that overstated the work physicians were performing, but Erlanger ignored the warnings, according to the complaint. 

Administrators allegedly resisted efforts by the chief compliance officer to hire an outside consultant to review its compensation models. Erlanger fired the compliance officer in 2019. 

The former chief compliance officer and another administrator filed a whistleblower lawsuit against Erlanger in 2021. The two administrators are relators in the government’s July 2024 lawsuit. 
 

How to Protect Yourself From Illegal Hospital Deals

The Erlanger case is the latest in a series of recent complaints by the federal government involving financial arrangements between hospitals and physicians.

In December 2023, Indianapolis-based Community Health Network Inc. agreed to pay the government $345 million to resolve claims that it paid physicians above fair market value and awarded bonuses tied to referrals in violation of the Stark Law. 

Also in 2023, Saginaw, Michigan–based Covenant HealthCare and two physicians paid the government $69 million to settle allegations that administrators engaged in improper financial arrangements with referring physicians and a physician-owned investment group. In another 2023 case, Massachusetts Eye and Ear in Boston agreed to pay $5.7 million to resolve claims that some of its physician compensation plans violated the Stark Law. 

Before you enter into a financial arrangement with a hospital, it’s also important to examine what percentile the aggregate compensation would reflect, law professor Mr. Sarraille said. The Erlanger case highlights federal officials’ suspicion of compensation, in aggregate, that exceeds the 90th percentile and increased attention to compensation that exceeds the 75th percentile, he said. 

To research compensation levels, doctors can review the Medical Group Management Association’s annual compensation report or search its compensation data. 

Before signing any contracts, Mr. Sarraille suggests, physicians should also consider whether the hospital shares the same values. Ask physicians at the hospital what they have to say about the hospital’s culture, vision, and values. Have physicians left the hospital after their practices were acquired? Consider speaking with them to learn why. 

Keep in mind that a doctor’s reputation could be impacted by a compliance complaint, regardless of whether it’s directed at the hospital and not the employed physician, Mr. Sarraille said. 

“The [Erlanger] complaint focuses on the compensation of specific, named physicians saying they were wildly overcompensated,” he said. “The implication is that they sold their referral power in exchange for a pay day. It’s a bad look, no matter how the case evolves from here.” 

Physicians could also face their own liability risk under the Stark Law and False Claims Act, depending on the circumstances. In the event of related quality-of-care issues, medical liability could come into play, Mr. Sarraille noted. In such cases, plaintiffs’ attorneys may see an opportunity to boost their claims with allegations that the patient harm was a function of “chasing compensation dollars,” Mr. Sarraille said. 

“Where that happens, plaintiff lawyers see the potential for crippling punitive damages, which might not be covered by an insurer,” he said.

A version of this article appeared on Medscape.com.

Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government’s complaint “serves as a warning” to healthcare providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to this news organization, Erlanger denied the allegations and said it would “vigorously” defend the lawsuit. 

“Erlanger paid physicians based on amounts that outside experts advised was fair market value,” Erlanger officials said in the statement. “Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims.”

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

“There is a tendency by physicians when contracting ... to rely on [hospitals’] perceived compliance and legal expertise,” Mr. Sarraille told this news organization. “This case illustrates the risks in doing so. Sometimes bigger doesn’t translate into more sophisticated or more effective from a compliance perspective.” 
 

Stark Law Prohibits Kickbacks

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

“HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase healthcare costs, and erode public trust in the healthcare system,” Ms. Miles said in a statement. 
 

Suit: Health System’s Money Woes Led to Illegal Arrangements

Erlanger’s financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government’s complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger’s agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government’s lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger’s physicians were expected to treat patients at Erlanger’s hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger’s CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.

In addition, Erlanger ignored patient safety concerns about some of its high revenue-generating physicians, the government claims. 

For instance, Erlanger received multiple complaints that a cardiothoracic surgeon was misusing an expensive form of life support in which pumps and oxygenators take over heart and lung function. Overuse of the equipment prolonged patients’ hospital stays and increased the hospital fees generated by the surgeon, according to the complaint. Staff also raised concerns about the cardiothoracic surgeon’s patient outcomes. 

But Erlanger disregarded the concerns and in 2018, increased the cardiothoracic surgeon’s retention bonus from $100,000 to $250,000, the suit alleges. A year later, the health system increased his base salary from $1,070,000 to $1,195,000.

Health care compensation and billing consultants alerted Erlanger that it was overpaying salaries and handing out bonuses based on measures that overstated the work physicians were performing, but Erlanger ignored the warnings, according to the complaint. 

Administrators allegedly resisted efforts by the chief compliance officer to hire an outside consultant to review its compensation models. Erlanger fired the compliance officer in 2019. 

The former chief compliance officer and another administrator filed a whistleblower lawsuit against Erlanger in 2021. The two administrators are relators in the government’s July 2024 lawsuit. 
 

How to Protect Yourself From Illegal Hospital Deals

The Erlanger case is the latest in a series of recent complaints by the federal government involving financial arrangements between hospitals and physicians.

In December 2023, Indianapolis-based Community Health Network Inc. agreed to pay the government $345 million to resolve claims that it paid physicians above fair market value and awarded bonuses tied to referrals in violation of the Stark Law. 

Also in 2023, Saginaw, Michigan–based Covenant HealthCare and two physicians paid the government $69 million to settle allegations that administrators engaged in improper financial arrangements with referring physicians and a physician-owned investment group. In another 2023 case, Massachusetts Eye and Ear in Boston agreed to pay $5.7 million to resolve claims that some of its physician compensation plans violated the Stark Law. 

Before you enter into a financial arrangement with a hospital, it’s also important to examine what percentile the aggregate compensation would reflect, law professor Mr. Sarraille said. The Erlanger case highlights federal officials’ suspicion of compensation, in aggregate, that exceeds the 90th percentile and increased attention to compensation that exceeds the 75th percentile, he said. 

To research compensation levels, doctors can review the Medical Group Management Association’s annual compensation report or search its compensation data. 

Before signing any contracts, Mr. Sarraille suggests, physicians should also consider whether the hospital shares the same values. Ask physicians at the hospital what they have to say about the hospital’s culture, vision, and values. Have physicians left the hospital after their practices were acquired? Consider speaking with them to learn why. 

Keep in mind that a doctor’s reputation could be impacted by a compliance complaint, regardless of whether it’s directed at the hospital and not the employed physician, Mr. Sarraille said. 

“The [Erlanger] complaint focuses on the compensation of specific, named physicians saying they were wildly overcompensated,” he said. “The implication is that they sold their referral power in exchange for a pay day. It’s a bad look, no matter how the case evolves from here.” 

Physicians could also face their own liability risk under the Stark Law and False Claims Act, depending on the circumstances. In the event of related quality-of-care issues, medical liability could come into play, Mr. Sarraille noted. In such cases, plaintiffs’ attorneys may see an opportunity to boost their claims with allegations that the patient harm was a function of “chasing compensation dollars,” Mr. Sarraille said. 

“Where that happens, plaintiff lawyers see the potential for crippling punitive damages, which might not be covered by an insurer,” he said.

A version of this article appeared on Medscape.com.

Strapped for cash and searching for new profits, Tennessee-based Erlanger Health System illegally paid excessive salaries to physicians in exchange for patient referrals, the US government alleged in a federal lawsuit.

Erlanger changed its compensation model to entice revenue-generating doctors, paying some two to three times the median salary for their specialty, according to the complaint. 

The physicians in turn referred numerous patients to Erlanger, and the health system submitted claims to Medicare for the referred services in violation of the Stark Law, according to the suit, filed in US District Court for the Western District of North Carolina. 

The government’s complaint “serves as a warning” to healthcare providers who try to boost profits through improper financial arrangements with referring physicians, said Tamala E. Miles, Special Agent in Charge for the US Department of Health and Human Services (HHS) Office of Inspector General (OIG).

In a statement provided to this news organization, Erlanger denied the allegations and said it would “vigorously” defend the lawsuit. 

“Erlanger paid physicians based on amounts that outside experts advised was fair market value,” Erlanger officials said in the statement. “Erlanger did not pay for referrals. A complete picture of the facts will demonstrate that the allegations lack merit and tell a very different story than what the government now claims.”

The Erlanger case is a reminder to physicians to consult their own knowledgeable advisors when considering financial arrangements with hospitals, said William Sarraille, JD, adjunct professor for the University of Maryland Francis King Carey School of Law in Baltimore and a regulatory consultant. 

“There is a tendency by physicians when contracting ... to rely on [hospitals’] perceived compliance and legal expertise,” Mr. Sarraille told this news organization. “This case illustrates the risks in doing so. Sometimes bigger doesn’t translate into more sophisticated or more effective from a compliance perspective.” 
 

Stark Law Prohibits Kickbacks

The Stark Law prohibits hospitals from billing the Centers for Medicare & Medicaid Services (CMS) for services referred by a physician with whom the hospital has an improper financial relationship.

CMS paid Erlanger about $27.8 million for claims stemming from the improper financial arrangements, the government contends. 

“HHS-OIG will continue to investigate such deals to prevent financial arrangements that could compromise impartial medical judgment, increase healthcare costs, and erode public trust in the healthcare system,” Ms. Miles said in a statement. 
 

Suit: Health System’s Money Woes Led to Illegal Arrangements

Erlanger’s financial troubles allegedly started after a previous run-in with the US government over false claims. 

In 2005, Erlanger Health System agreed to pay the government $40 million to resolve allegations that it knowingly submitted false claims to Medicare, according to the government’s complaint. At the time, Erlanger entered into a Corporate Integrity Agreement (CIA) with the OIG that required Erlanger to put controls in place to ensure its financial relationships did not violate the Stark Law. 

Erlanger’s agreement with OIG ended in 2010. Over the next 3 years, the health system lost nearly $32 million and in fiscal year 2013, had only 65 days of cash on hand, according to the government’s lawsuit. 

Beginning in 2013, Erlanger allegedly implemented a strategy to increase profits by employing more physicians, particularly specialists from competing hospitals whose patients would need costly hospital stays, according to the complaint. 

Once hired, Erlanger’s physicians were expected to treat patients at Erlanger’s hospitals and refer them to other providers within the health system, the suit claims. Erlanger also relaxed or eliminated the oversight and controls on physician compensation put in place under the CIA. For example, Erlanger’s CEO signed some compensation contracts before its chief compliance officer could review them and no longer allowed the compliance officer to vote on whether to approve compensation arrangements, according to the complaint. 

Erlanger also changed its compensation model to include large salaries for medical director and academic positions and allegedly paid such salaries to physicians without ensuring the required work was performed. As a result, Erlanger physicians with profitable referrals were among the highest paid in the nation for their specialties, the government claims. For example, according to the complaint:

• Erlanger paid an electrophysiologist an annual clinical salary of $816,701, a medical director salary of $101,080, an academic salary of $59,322, and a productivity incentive based on work relative value units (wRVUs). The medical director and academic salaries paid were near the 90th percentile of comparable salaries in the specialty.
• The health system paid a neurosurgeon a base salary of $654,735, a productivity incentive based on wRVUs, and payments for excess call coverage ranging from $400 to $1000 per 24-hour shift. In 2016, the neurosurgeon made $500,000 in excess call payments.
• Erlanger paid a cardiothoracic surgeon a base clinical salary of $1,070,000, a sign-on bonus of $150,000, a retention bonus of $100,000 (payable in the 4th year of the contract), and a program incentive of up to $150,000 per year.

In addition, Erlanger ignored patient safety concerns about some of its high revenue-generating physicians, the government claims. 

For instance, Erlanger received multiple complaints that a cardiothoracic surgeon was misusing an expensive form of life support in which pumps and oxygenators take over heart and lung function. Overuse of the equipment prolonged patients’ hospital stays and increased the hospital fees generated by the surgeon, according to the complaint. Staff also raised concerns about the cardiothoracic surgeon’s patient outcomes. 

But Erlanger disregarded the concerns and in 2018, increased the cardiothoracic surgeon’s retention bonus from $100,000 to $250,000, the suit alleges. A year later, the health system increased his base salary from $1,070,000 to $1,195,000.

Health care compensation and billing consultants alerted Erlanger that it was overpaying salaries and handing out bonuses based on measures that overstated the work physicians were performing, but Erlanger ignored the warnings, according to the complaint. 

Administrators allegedly resisted efforts by the chief compliance officer to hire an outside consultant to review its compensation models. Erlanger fired the compliance officer in 2019. 

The former chief compliance officer and another administrator filed a whistleblower lawsuit against Erlanger in 2021. The two administrators are relators in the government’s July 2024 lawsuit. 
 

How to Protect Yourself From Illegal Hospital Deals

The Erlanger case is the latest in a series of recent complaints by the federal government involving financial arrangements between hospitals and physicians.

In December 2023, Indianapolis-based Community Health Network Inc. agreed to pay the government $345 million to resolve claims that it paid physicians above fair market value and awarded bonuses tied to referrals in violation of the Stark Law. 

Also in 2023, Saginaw, Michigan–based Covenant HealthCare and two physicians paid the government $69 million to settle allegations that administrators engaged in improper financial arrangements with referring physicians and a physician-owned investment group. In another 2023 case, Massachusetts Eye and Ear in Boston agreed to pay $5.7 million to resolve claims that some of its physician compensation plans violated the Stark Law. 

Before you enter into a financial arrangement with a hospital, it’s also important to examine what percentile the aggregate compensation would reflect, law professor Mr. Sarraille said. The Erlanger case highlights federal officials’ suspicion of compensation, in aggregate, that exceeds the 90th percentile and increased attention to compensation that exceeds the 75th percentile, he said. 

To research compensation levels, doctors can review the Medical Group Management Association’s annual compensation report or search its compensation data. 

Before signing any contracts, Mr. Sarraille suggests, physicians should also consider whether the hospital shares the same values. Ask physicians at the hospital what they have to say about the hospital’s culture, vision, and values. Have physicians left the hospital after their practices were acquired? Consider speaking with them to learn why. 

Keep in mind that a doctor’s reputation could be impacted by a compliance complaint, regardless of whether it’s directed at the hospital and not the employed physician, Mr. Sarraille said. 

“The [Erlanger] complaint focuses on the compensation of specific, named physicians saying they were wildly overcompensated,” he said. “The implication is that they sold their referral power in exchange for a pay day. It’s a bad look, no matter how the case evolves from here.” 

Physicians could also face their own liability risk under the Stark Law and False Claims Act, depending on the circumstances. In the event of related quality-of-care issues, medical liability could come into play, Mr. Sarraille noted. In such cases, plaintiffs’ attorneys may see an opportunity to boost their claims with allegations that the patient harm was a function of “chasing compensation dollars,” Mr. Sarraille said. 

“Where that happens, plaintiff lawyers see the potential for crippling punitive damages, which might not be covered by an insurer,” he said.

A version of this article appeared on Medscape.com.

In a case that spotlights the importance of comprehensive financial controls in medical offices, a leading New York City emergency medicine physician stands accused of using his business credit card to steal nearly $1.5 million from his clinical practice and spend it on cash advances, personal travel, lavish pet services, and more.

Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”

Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.

Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.

The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.

“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.

SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.

Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
 

Size of Alleged Theft Is ‘Very Unusual’

David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”

William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).

Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).

The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
 

Even Small Medical Offices Can Act to Prevent Fraud

What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”

Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”

One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
 

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

In a case that spotlights the importance of comprehensive financial controls in medical offices, a leading New York City emergency medicine physician stands accused of using his business credit card to steal nearly $1.5 million from his clinical practice and spend it on cash advances, personal travel, lavish pet services, and more.

Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”

Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.

Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.

The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.

“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.

SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.

Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
 

Size of Alleged Theft Is ‘Very Unusual’

David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”

William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).

Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).

The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
 

Even Small Medical Offices Can Act to Prevent Fraud

What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”

Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”

One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
 

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

In a case that spotlights the importance of comprehensive financial controls in medical offices, a leading New York City emergency medicine physician stands accused of using his business credit card to steal nearly $1.5 million from his clinical practice and spend it on cash advances, personal travel, lavish pet services, and more.

Michael Lucchesi, MD, who had served as chairman of Emergency Medicine at SUNY Downstate Medical Center in New York City, was arraigned on July 9 and pleaded not guilty. Dr. Lucchesi’s attorney, Earl Ward, did not respond to messages from this news organization, but he told the New York Post that “the funds he used were not stolen funds.”

Dr. Lucchesi, who’s in his late 60s, faces nine counts of first- and second-degree grand larceny, first-degree falsifying business records, and third-degree criminal tax fraud. According to a press statement from the district attorney of Kings County, which encompasses the borough of Brooklyn, Dr. Lucchesi is accused of using his clinical practice’s business card for cash advances (about $115,000), high-end pet care ($176,000), personal travel ($348,000), gym membership and personal training ($109,000), catering ($52,000), tuition payments for his children ($46,000), and other expenses such as online shopping, flowers, liquor, and electronics.

Most of the alleged pet care spending — $120,000 — went to the Green Leaf Pet Resort, which has two locations in New Jersey, including one with “56 acres of nature and lots of tail wagging.” Some of the alleged spending on gym membership was at the New York Sports Clubs chain, where monthly membership tops out at $139.99.

The alleged spending occurred between 2016 and 2023 and was discovered by SUNY Downstate during an audit. Dr. Lucchesi reportedly left his position at the hospital, where he made $399,712 in 2022 as a professor, according to public records.

“As a high-ranking doctor at this vital healthcare institution, this defendant was entrusted with access to significant funds, which he allegedly exploited, stealing more than 1 million dollars to pay for a lavish lifestyle,” District Attorney Eric Gonzalez said in a statement.

SUNY Downstate is in a fight for its life amid efforts by New York Governor Kathy Hochul to shut it down. According to The New York Times, it is the only state-run hospital in New York City.

Dr. Lucchesi, who had previously served as the hospital’s chief medical officer and acting head, was released without bail. His next court date is September 25, 2024.
 

Size of Alleged Theft Is ‘Very Unusual’

David P. Weber, JD, DBA, a professor and fraud specialist at Salisbury University, Salisbury, Maryland, told this news organization that the fraudulent use of a business or purchase credit card is a form of embezzlement and “one of the most frequently seen types of frauds against organizations.”

William J. Kresse, JD, MSA, CPA/CFF, who studies fraud at Governors State University in University Park, Illinois, noted in an interview with this news organization that the high amount of alleged fraud in this case is “very unusual,” as is the period it is said to have occurred (over 6 years).

Mr. Kresse highlighted a 2024 report by the Association of Certified Fraud Examiners, which found that the median fraud loss in healthcare, on the basis of 117 cases, is $100,000. The most common form of fraud in the industry is corruption (47%), followed by billing (38%), noncash theft such as inventory (22%), and expense reimbursement (21%).

The details of the current case suggest that “SUNY Downstate had weak or insufficient internal controls to prevent this type of fraud,” Salisbury University’s Mr. Weber said. “However, research also makes clear that the tenure and position of the perpetrator play a significant role in the size of the fraud. Internal controls are supposed to apply to all employees, but the higher in the organization the perpetrator is, the easier it can be to engage in fraud.”
 

Even Small Medical Offices Can Act to Prevent Fraud

What can be done to prevent this kind of fraud? “Each employee should be required to submit actual receipts or scanned copies, and the reimbursement requests should be reviewed and inputted by a separate department or office of the organization to ensure that the expenses are legitimate,” Mr. Weber said. “In addition, all credit card statements should be available for review by the organization either simultaneously with the bill going to the employee or available for audit or review at any time without notification to the employee. Expenses that are in certain categories should be prohibited automatically and coded to the card so such a charge is rejected by the credit card bank.”

Smaller businesses — like many medical practices — may not have the manpower to handle these roles. In that case, Mr. Weber said, “The key is segregation or separation of duties. The bookkeeper cannot be the person receiving the bank statements, the payments from patients, and the invoices from vendors. There needs to be at least one other person in the loop to have some level of control.”

One strategy, he said, “is that the practice should institute a policy that only the doctor or owner of the practice can receive the mail, not the bookkeeper. Even if the practice leader does not actually review the bank statements, simply opening them before handing them off to the bookkeeper can provide a level of deterrence [since] the employee may get caught if someone else is reviewing the bank statements.”
 

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

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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