Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

Seventeen years ago, Philip Segal, a retired accountant from suburban Toronto, Canada, was diagnosed with prostate cancer in a private clinic. After rejecting brachytherapy recommended by an oncologist, he went on active surveillance to watch, but not treat, the Gleason 6 (grade group 1) tumor. As he approaches his 80th birthday later this year, Mr. Segal said he plans to maintain the status quo. “It definitely brings me some peace of mind. I’d rather do that than not follow it and kick myself if there was a serious change,” he said.

Meanwhile, 2 years ago and 200 miles away in suburban Detroit, Bruno Barrey, a robotics engineer, was diagnosed with three cores of Gleason 6 and went on active surveillance.

Six months after the original diagnosis, however, Mr. Barrey, 57, underwent a follow-up biopsy. This time, all 16 cores were positive, with a mix of low-risk Gleason 6 and more advanced Gleason 3 + 4 lesions. His tumor was so large he underwent radiation therapy in 2023, ending his brief stint on the monitoring approach.

The two cases illustrate the complicated truth of active surveillance. For some men, the strategy can prove to be short-lived, perhaps 5 years or less, or a life-long approach lasting until the man dies from another cause.

Which kind of race a man will run depends on a wide range of factors: His comfort level living with a cancer, or at least a tumor that might well evolve into an aggressive malignancy, changes in his prostate-specific antigen (PSA) level and results of a magnetic resonance imaging test, the volume of his cancer, results of genetic testing of the patient himself and his lesion, and his urologist’s philosophy about surveillance. Where a patient lives matters, too, because variations in surveillance levels exist in different geographic areas, domestically and internationally.

“Active surveillance is a strategy of monitoring until it is necessary to be treated. For some people, it is very short, and for others, essentially indefinite,” said Michael Leapman, MD, clinical lead at Yale Cancer Center in New Haven, Connecticut. “While there are differences, I think they are mainly about who is the ideal patient.”

Most studies show that roughly half of men in the United States who go on active surveillance abandon it within 5 years of diagnosis. Rashid Sayyid, MD, a clinical fellow at the University of Toronto, Canada, found in a paper presented to the American Urological Association in 2022 that the number leaving active surveillance increased to nearly two thirds at 10 years.

Peter Carroll, MD, a urologist at the University of California, San Francisco, and a pioneer in the active surveillance in the late 1990s, said the major reason men abandon the strategy is because monitoring reveals the presence of a more aggressive cancer, typically a grade group 2 (Gleason 3 + 4) lesion. But other reasons include anxiety and other emotional distress and upgrades in blood levels of PSA and increases in the rating scale for MRI for the likelihood of the presence of clinically significant prostate cancer.

Laurence Klotz, MD, of the University of Toronto, Toronto, Ontario, who coined the term active surveillance strategy in 1997 and published the first studies in the early 2000s, said it is important to consider when the data on surveillance were collected.

Since 2013, when MRI began to be adopted as a surveillance modality for men with prostate cancer, the dropout rate began declining. The reason? According to Dr. Klotz, MRIs and targeted biopsies result in greater accuracy in staging the disease, determining which patients need to be biopsied, which helps some men avoid being diagnosed to begin with.

Dr. Klotz cited as an example of the emerging change a 2020 study in the Journal of Urology, which found a 24% dropout rate for surveillance at 5 years, 36% at 10 years, and 42% at 15 years in a series of 2664 grade group 1 patients on active surveillance at Memorial Sloan Kettering Cancer Center in New York City from 2000 to 2017.

Dr. Leapman cited a 2023 study in JNCI Cancer Spectrum using the National Cancer Database that found a decline in the percentage of patients who had grade group 1 in biopsies from 45% in 2010 to 25% in 2019.

“There is more judicious use of PSA testing and biopsy in individuals who are more likely to have significant prostate cancer,” Dr. Leapman told this news organization. “And MRI could also play a role by finding more high-grade cancers that would have otherwise been hidden.”

The changing statistics of prostate cancer also may reflect decreases in screening in response to a 2012 statement from the US Preventive Services Task Force advising against PSA testing. The American Cancer Society in January 2023 said that statement could be driving more diagnoses of late-stage disease, which has been surging for the first time in two decades, especially among Black men.

Dr. Sayyid said patients must be selected carefully for active surveillance. And he said urologists should not promise their active surveillance patients that they will avoid treatment. “There are numerous factors at stake that influence the ultimate outcome,” he said.

Progression of Gleason scores is estimated at 1%-2% per year, Dr. Sayyid added. When active surveillance fails in the short to medium term — 5-10 years — the reason usually is that higher-grade cancers with Gleason 3 + 4 or above were initially missed.

Dr. Sayyid said he counsels patients aged 70 years and older differently than those in their 50s, telling younger patients they are more likely to need treatment eventually than the older patients.

Factors that can affect the longevity of active surveillance include the presence or absence of germline mutations and the overall health and life expectancy and comorbidities such as heart disease and diabetes in a given patient, he said.

Urologists hold varying philosophies here, especially involving younger patients and the presence of any level of Gleason 4 cancer.

William Catalona, MD, of Northwestern University Feinberg School of Medicine in Chicago, Illinois, who developed the concept of mass screening with PSA testing, originally opposed active surveillance. In recent years, he has modified his views but still takes a more conservative approach.

“I consider active surveillance a foolish strategy or, at best, a short-term strategy for young, otherwise healthy men, especially those having any Gleason pattern 4 disease.”

“More than half will ultimately convert to active treatment, some too late, and will require multiple treatments with multiple side effects. Some will develop metastases, and some will die of prostate cancer.”

Dr. Sayyid takes a more liberal approach. “I would counsel an eligible patient considering active surveillance that at the current time, I see no strong reason why you should be subjected to treatment and the associated side effects,” he said. “And as long as your overall disease ‘state’ [the combination of grade, volume, PSA, and imaging tests] remains relatively stable, there should be no reason for us to ‘jump ship’. In my practice, another term for active surveillance is ‘active partnership’ — working together to decide if this is a sprint or a lifelong marathon.”

Dr. Carroll reported research funding from the National Institutes of Health.

A version of this article appeared on Medscape.com.

A virtual visit with one’s own primary care physician (PCP) is less likely to result in a subsequent emergency department (ED) visit compared with a visit with an outside physician, research suggested.

A cohort study of more than 5 million Ontario residents with a PCP found that those who had a virtual visit with a physician other than their own were 66% more likely to visit the ED within 7 days.

“Because our study relied on health administrative data only, we cannot know for sure how necessary each ED visit was,” lead author Lauren Lapointe-Shaw, MD, PhD, assistant professor of medicine at the University of Toronto, told this news organization. “We did note, however, that the association between the type of virtual visit and ED use was stronger for low-acuity ED visits — those that are most likely to have been avoided with timely access to a PCP familiar with the patient.”

The study was published online on December 27, 2023, in JAMA Network Open.
 

Existing Relationship Beneficial

To investigate potential differences in subsequent ED use between patients who had a virtual visit with their own PCP and patients who had a virtual visit with an outside physician, the researchers conducted a propensity score–matched cohort study among all Ontario residents with a PCP who had a virtual PCP visit from April 2021 through March 2022. In a secondary analysis, visits with one’s own physician were compared with visits with a physician working in direct-to-consumer telemedicine. The primary outcome was an ED visit within 7 days after the virtual visit.

Among 5,229,240 patients, 79.8% (mean age, 49.3 years; 58% women) had a virtual visit with their own physician, and 20.2% (mean age, 41.8 years; 57.4% women) had a virtual visit with an outside physician.

In the matched cohort of 1,885,966 patients, those who saw an outside physician were 66% more likely to visit an ED within 7 days than those who had a virtual visit with their own physician (3.3% vs 2.0%). This corresponds to one additional ED visit for every 77 virtual visits with an outside physician. The increased risk was greater for low-acuity patients (0.8% vs 0.4%; relative risk [RR], 1.90) than for high-acuity patients (0.7% vs 0.5%; RR, 1.46).

Increased use of the ED associated with low-continuity virtual visits was front-loaded in the first few days. Therefore, the authors suggested that virtual visits may serve a triaging function, enabling the identification of patients who would benefit from an in-person assessment.

Patients who had an outside-physician virtual visit also were more likely than those with an own-physician visit to have an in-person PCP visit within 7 days of the virtual visit (6.1% vs 4.9%; RR, 1.25), but that visit was less likely to be with their own physician (1.1% vs 4.2%; RR, 0.25).

Similarly, they were nearly twice as likely to have a repeat virtual visit within 7 days (8.9% vs 4.7%; RR, 1.88), but again, the visit was less likely to be with their own physician (2.1% vs 4.2%; RR, 0.50).

A subgroup analysis showed that the increased risk for a 7-day ED visit associated with an outside-physician virtual visit was greater for younger age groups. Children and adolescents were at the highest risk (RR, 1.96), followed by adults aged 18-64 years (RR, 1.69) and those aged 65 years or older (RR, 1.40).

Furthermore, the increased risk for ED visits was greater when comparing patients with direct-to-consumer telemedicine visits with patients with own-physician visits (RR, 2.99). As in the main cohort, the increased risk was front-loaded in the first 2 days.

“Our findings add to a growing body of evidence suggesting that virtual care is most efficient when used within an existing therapeutic relationship,” said Dr. Lapointe-Shaw. The team currently is studying patient outcomes of physicians who provide walk-in clinic care.
 

Insurance Coverage Questions

Asif Ansari, MD, regional medical director at Montefiore Medical Group in New York, told this news organization that his experience as a PCP “has led to the conclusion that care delivered by a patient’s own provider is superior, whether in person or via telemedicine. Nothing can replace that relationship, level of familiarity, and access to personal health information.” Dr. Ansari was not involved in the study.

The study did not include virtual visits with another physician in the same clinical group, he noted. A physician in the same group “likely operates on the same electronic health record, which contains valuable information including medical problem lists, lab results, medication lists, and allergies. Theoretically, access to such information would lower ED utilization. This is a significant missing piece when we look at the overall impact of virtual care.”

More patients are now looking for the convenience and access that virtual medicine provides, noted Dr. Ansari. “If we do not appropriately leverage this tool in primary care, we will see more and more external entities enter the field, leading to further care fragmentation.”

“The rate-limiting step may be what the insurers cover as they review future trends in utilization and quality metrics,” he added. “It is important [for us] as clinicians to thoughtfully engage and help determine where the future leads us in the interest of our patients.”

Steven Shook, MD, lead for virtual health at Cleveland Clinic in Ohio, also commented on the study for this news organization. He noted that without additional information, “it’s hard to say that the two groups they’re comparing are identical. For example, patients who are self-selecting to do virtual visits with an outside physician or direct-to-consumer telemedicine may have good reasons — maybe they can’t see their own doctor in the hours available, or maybe their own doctor doesn’t do virtual visits. We don’t know the urgency of the need to see a doctor. So, lots of factors aren’t included or measured in this study.”

Future studies need to assess how virtual visits affect the total cost of care, Dr. Shook added. “It’s not just whether the patients end up in the ED, but whether we may be more likely to order an MRI because we can’t lay hands on the patient. And we need to know how the need for any additional tests affects the patient’s diagnosis and outcome.”

Overall, Dr. Shook said, “virtual visits need to be integrated into patient care. They need to be part of a comprehensive program that primary care practices provide to a patient, to balance the access, convenience, and continuity that comes with that.”

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care. The study also received funding from the MOH through a grant awarded to Dr. Lapointe-Shaw and a project grant from the Canadian Institutes of Health Research awarded to Dr. Lapointe-Shaw and another coauthor. Dr. Lapointe-Shaw, Dr. Ansari, and Dr. Shook reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A virtual visit with one’s own primary care physician (PCP) is less likely to result in a subsequent emergency department (ED) visit compared with a visit with an outside physician, research suggested.

A cohort study of more than 5 million Ontario residents with a PCP found that those who had a virtual visit with a physician other than their own were 66% more likely to visit the ED within 7 days.

“Because our study relied on health administrative data only, we cannot know for sure how necessary each ED visit was,” lead author Lauren Lapointe-Shaw, MD, PhD, assistant professor of medicine at the University of Toronto, told this news organization. “We did note, however, that the association between the type of virtual visit and ED use was stronger for low-acuity ED visits — those that are most likely to have been avoided with timely access to a PCP familiar with the patient.”

The study was published online on December 27, 2023, in JAMA Network Open.
 

Existing Relationship Beneficial

To investigate potential differences in subsequent ED use between patients who had a virtual visit with their own PCP and patients who had a virtual visit with an outside physician, the researchers conducted a propensity score–matched cohort study among all Ontario residents with a PCP who had a virtual PCP visit from April 2021 through March 2022. In a secondary analysis, visits with one’s own physician were compared with visits with a physician working in direct-to-consumer telemedicine. The primary outcome was an ED visit within 7 days after the virtual visit.

Among 5,229,240 patients, 79.8% (mean age, 49.3 years; 58% women) had a virtual visit with their own physician, and 20.2% (mean age, 41.8 years; 57.4% women) had a virtual visit with an outside physician.

In the matched cohort of 1,885,966 patients, those who saw an outside physician were 66% more likely to visit an ED within 7 days than those who had a virtual visit with their own physician (3.3% vs 2.0%). This corresponds to one additional ED visit for every 77 virtual visits with an outside physician. The increased risk was greater for low-acuity patients (0.8% vs 0.4%; relative risk [RR], 1.90) than for high-acuity patients (0.7% vs 0.5%; RR, 1.46).

Increased use of the ED associated with low-continuity virtual visits was front-loaded in the first few days. Therefore, the authors suggested that virtual visits may serve a triaging function, enabling the identification of patients who would benefit from an in-person assessment.

Patients who had an outside-physician virtual visit also were more likely than those with an own-physician visit to have an in-person PCP visit within 7 days of the virtual visit (6.1% vs 4.9%; RR, 1.25), but that visit was less likely to be with their own physician (1.1% vs 4.2%; RR, 0.25).

Similarly, they were nearly twice as likely to have a repeat virtual visit within 7 days (8.9% vs 4.7%; RR, 1.88), but again, the visit was less likely to be with their own physician (2.1% vs 4.2%; RR, 0.50).

A subgroup analysis showed that the increased risk for a 7-day ED visit associated with an outside-physician virtual visit was greater for younger age groups. Children and adolescents were at the highest risk (RR, 1.96), followed by adults aged 18-64 years (RR, 1.69) and those aged 65 years or older (RR, 1.40).

Furthermore, the increased risk for ED visits was greater when comparing patients with direct-to-consumer telemedicine visits with patients with own-physician visits (RR, 2.99). As in the main cohort, the increased risk was front-loaded in the first 2 days.

“Our findings add to a growing body of evidence suggesting that virtual care is most efficient when used within an existing therapeutic relationship,” said Dr. Lapointe-Shaw. The team currently is studying patient outcomes of physicians who provide walk-in clinic care.
 

Insurance Coverage Questions

Asif Ansari, MD, regional medical director at Montefiore Medical Group in New York, told this news organization that his experience as a PCP “has led to the conclusion that care delivered by a patient’s own provider is superior, whether in person or via telemedicine. Nothing can replace that relationship, level of familiarity, and access to personal health information.” Dr. Ansari was not involved in the study.

The study did not include virtual visits with another physician in the same clinical group, he noted. A physician in the same group “likely operates on the same electronic health record, which contains valuable information including medical problem lists, lab results, medication lists, and allergies. Theoretically, access to such information would lower ED utilization. This is a significant missing piece when we look at the overall impact of virtual care.”

More patients are now looking for the convenience and access that virtual medicine provides, noted Dr. Ansari. “If we do not appropriately leverage this tool in primary care, we will see more and more external entities enter the field, leading to further care fragmentation.”

“The rate-limiting step may be what the insurers cover as they review future trends in utilization and quality metrics,” he added. “It is important [for us] as clinicians to thoughtfully engage and help determine where the future leads us in the interest of our patients.”

Steven Shook, MD, lead for virtual health at Cleveland Clinic in Ohio, also commented on the study for this news organization. He noted that without additional information, “it’s hard to say that the two groups they’re comparing are identical. For example, patients who are self-selecting to do virtual visits with an outside physician or direct-to-consumer telemedicine may have good reasons — maybe they can’t see their own doctor in the hours available, or maybe their own doctor doesn’t do virtual visits. We don’t know the urgency of the need to see a doctor. So, lots of factors aren’t included or measured in this study.”

Future studies need to assess how virtual visits affect the total cost of care, Dr. Shook added. “It’s not just whether the patients end up in the ED, but whether we may be more likely to order an MRI because we can’t lay hands on the patient. And we need to know how the need for any additional tests affects the patient’s diagnosis and outcome.”

Overall, Dr. Shook said, “virtual visits need to be integrated into patient care. They need to be part of a comprehensive program that primary care practices provide to a patient, to balance the access, convenience, and continuity that comes with that.”

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care. The study also received funding from the MOH through a grant awarded to Dr. Lapointe-Shaw and a project grant from the Canadian Institutes of Health Research awarded to Dr. Lapointe-Shaw and another coauthor. Dr. Lapointe-Shaw, Dr. Ansari, and Dr. Shook reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A virtual visit with one’s own primary care physician (PCP) is less likely to result in a subsequent emergency department (ED) visit compared with a visit with an outside physician, research suggested.

A cohort study of more than 5 million Ontario residents with a PCP found that those who had a virtual visit with a physician other than their own were 66% more likely to visit the ED within 7 days.

“Because our study relied on health administrative data only, we cannot know for sure how necessary each ED visit was,” lead author Lauren Lapointe-Shaw, MD, PhD, assistant professor of medicine at the University of Toronto, told this news organization. “We did note, however, that the association between the type of virtual visit and ED use was stronger for low-acuity ED visits — those that are most likely to have been avoided with timely access to a PCP familiar with the patient.”

The study was published online on December 27, 2023, in JAMA Network Open.
 

Existing Relationship Beneficial

To investigate potential differences in subsequent ED use between patients who had a virtual visit with their own PCP and patients who had a virtual visit with an outside physician, the researchers conducted a propensity score–matched cohort study among all Ontario residents with a PCP who had a virtual PCP visit from April 2021 through March 2022. In a secondary analysis, visits with one’s own physician were compared with visits with a physician working in direct-to-consumer telemedicine. The primary outcome was an ED visit within 7 days after the virtual visit.

Among 5,229,240 patients, 79.8% (mean age, 49.3 years; 58% women) had a virtual visit with their own physician, and 20.2% (mean age, 41.8 years; 57.4% women) had a virtual visit with an outside physician.

In the matched cohort of 1,885,966 patients, those who saw an outside physician were 66% more likely to visit an ED within 7 days than those who had a virtual visit with their own physician (3.3% vs 2.0%). This corresponds to one additional ED visit for every 77 virtual visits with an outside physician. The increased risk was greater for low-acuity patients (0.8% vs 0.4%; relative risk [RR], 1.90) than for high-acuity patients (0.7% vs 0.5%; RR, 1.46).

Increased use of the ED associated with low-continuity virtual visits was front-loaded in the first few days. Therefore, the authors suggested that virtual visits may serve a triaging function, enabling the identification of patients who would benefit from an in-person assessment.

Patients who had an outside-physician virtual visit also were more likely than those with an own-physician visit to have an in-person PCP visit within 7 days of the virtual visit (6.1% vs 4.9%; RR, 1.25), but that visit was less likely to be with their own physician (1.1% vs 4.2%; RR, 0.25).

Similarly, they were nearly twice as likely to have a repeat virtual visit within 7 days (8.9% vs 4.7%; RR, 1.88), but again, the visit was less likely to be with their own physician (2.1% vs 4.2%; RR, 0.50).

A subgroup analysis showed that the increased risk for a 7-day ED visit associated with an outside-physician virtual visit was greater for younger age groups. Children and adolescents were at the highest risk (RR, 1.96), followed by adults aged 18-64 years (RR, 1.69) and those aged 65 years or older (RR, 1.40).

Furthermore, the increased risk for ED visits was greater when comparing patients with direct-to-consumer telemedicine visits with patients with own-physician visits (RR, 2.99). As in the main cohort, the increased risk was front-loaded in the first 2 days.

“Our findings add to a growing body of evidence suggesting that virtual care is most efficient when used within an existing therapeutic relationship,” said Dr. Lapointe-Shaw. The team currently is studying patient outcomes of physicians who provide walk-in clinic care.
 

Insurance Coverage Questions

Asif Ansari, MD, regional medical director at Montefiore Medical Group in New York, told this news organization that his experience as a PCP “has led to the conclusion that care delivered by a patient’s own provider is superior, whether in person or via telemedicine. Nothing can replace that relationship, level of familiarity, and access to personal health information.” Dr. Ansari was not involved in the study.

The study did not include virtual visits with another physician in the same clinical group, he noted. A physician in the same group “likely operates on the same electronic health record, which contains valuable information including medical problem lists, lab results, medication lists, and allergies. Theoretically, access to such information would lower ED utilization. This is a significant missing piece when we look at the overall impact of virtual care.”

More patients are now looking for the convenience and access that virtual medicine provides, noted Dr. Ansari. “If we do not appropriately leverage this tool in primary care, we will see more and more external entities enter the field, leading to further care fragmentation.”

“The rate-limiting step may be what the insurers cover as they review future trends in utilization and quality metrics,” he added. “It is important [for us] as clinicians to thoughtfully engage and help determine where the future leads us in the interest of our patients.”

Steven Shook, MD, lead for virtual health at Cleveland Clinic in Ohio, also commented on the study for this news organization. He noted that without additional information, “it’s hard to say that the two groups they’re comparing are identical. For example, patients who are self-selecting to do virtual visits with an outside physician or direct-to-consumer telemedicine may have good reasons — maybe they can’t see their own doctor in the hours available, or maybe their own doctor doesn’t do virtual visits. We don’t know the urgency of the need to see a doctor. So, lots of factors aren’t included or measured in this study.”

Future studies need to assess how virtual visits affect the total cost of care, Dr. Shook added. “It’s not just whether the patients end up in the ED, but whether we may be more likely to order an MRI because we can’t lay hands on the patient. And we need to know how the need for any additional tests affects the patient’s diagnosis and outcome.”

Overall, Dr. Shook said, “virtual visits need to be integrated into patient care. They need to be part of a comprehensive program that primary care practices provide to a patient, to balance the access, convenience, and continuity that comes with that.”

The study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health (MOH) and the Ministry of Long-Term Care. The study also received funding from the MOH through a grant awarded to Dr. Lapointe-Shaw and a project grant from the Canadian Institutes of Health Research awarded to Dr. Lapointe-Shaw and another coauthor. Dr. Lapointe-Shaw, Dr. Ansari, and Dr. Shook reported no conflicts of interest.

A version of this article appeared on Medscape.com.

ORLANDO — People with epilepsy are more likely to decline cognitively compared with those without epilepsy, new research suggests.

Results of the large, longitudinal study show that seizures predicted earlier conversion time from normal cognition to mild cognitive impairment (MCI) but were not associated with conversion from MCI to dementia.

“Modifiable cardiovascular risk factors such as hypertension and diabetes need to be treated more aggressively because they can impact cognition, but epilepsy is another risk factor that needs to be treated in a timely fashion because it appears to be also associated with cognitive impairment,” said study investigator Ifrah Zawar MD, assistant professor, Department of Neurology, University of Virginia in Charlottesville.

The study (abstract #2.172) was presented on December 2 at the American Epilepsy Society annual meeting.
 

An Understudied Issue

Comorbid seizures occur in up to 64% of those with dementia, and patients with dementia and epilepsy have a more aggressive disease course, faster cognitive decline, and more severe neuronal loss, Dr. Zawar told Medscape Medical News.

But the impact of seizures on the conversion of cognitively healthy to MCI and from MCI to dementia, after accounting for cardiovascular risk factors, has not been well studied.

Researchers analyzed longitudinal data of 13,726 patients, mean age about 70 years, who were cognitively healthy or had mild cognitive impairment (MCI). Participants were recruited from 39 Alzheimer’s Disease (AD) centers in the United States from 2005 to 2021. 

Investigators categorized participants into three groups: active (having had seizures in the past year and/or requiring active treatment; N = 118), resolved (not on any treatment for the past year and not having seizures; N = 226), and no seizures (never having had seizures; N = 13,382).

The primary outcome was conversion from cognitively healthy to MCI/dementia and from MCI to dementia in those with and without active epilepsy and resolved epilepsy.

Factors associated with conversion from cognitively healthy to MCI among those with current or active epilepsy included older age (P <.001 for ages 60-80 years and P =.002 for age 80 years or older vs younger than 60 years), male sex (P <.001), lower education (P <.001), hypertension (P <.001), and diabetes (P <.001).

The hazard ratio (HR) for earlier conversion from healthy to worse cognition among those with active epilepsy was 1.76 (95% CI, 1.38-2.24; P <.001), even after accounting for risk factors.

Kaplan-Meier curves showed that the median time to convert from healthy cognition to MCI among people with active epilepsy was about 5 years compared with about 9 years for those with resolved epilepsy and 10.5 years for those without epilepsy.

The story was similar for faster conversion from MCI to dementia. Compared with having no epilepsy, the HR for faster conversion for active epilepsy was 1.44 (95% CI, 1.20-1.73; P <.001).

In addition, the median time to conversion from MCI to dementia was about 3 years for those with active epilepsy compared with about 5 years for those with resolved epilepsy and about 5 years for those without epilepsy.

“It’s important for physicians to understand that uncontrolled epilepsy or active epilepsy is going to impact patients’ cognition adversely, which in itself is associated with increased comorbidity and mortality,” said Dr. Zawar.

The mechanism driving the acceleration to worse cognition in people with epilepsy is “complicated and involves a multitude of factors,” she said.

The researchers did not specifically investigate how use of antiseizure medications correlated with cognitive outcomes, but Dr. Zawar believes that “epilepsy in itself impacts cognition.”

The researchers also didn’t have EEG data for study participants who were recruited from Alzheimer’s disease centers where EEGs aren’t routinely carried out, so such data for many patients may not necessarily exist, said Dr. Zawar.
 

Important Research

Commenting for this news organization, Bruce Hermann, PhD, professor emeritus, Department of Neurology, University of Wisconsin School of Medicine and Public Health,  said that the study is important because of the, “tremendous interest and concern about aging with epilepsy.”

“We want to know how people with chronic epilepsy age cognitively and what’s the cognitive course of those who have late onset epilepsy, particularly those with unknown etiology,” he added. 

Dr. Hermann noted that much of the research in this area has been relatively small and single-center investigations. 

“These larger-scale investigations from outside the epilepsy community are so important because they have data on large numbers of subjects, they have cognitive data, and follow-ups over long periods of time, and they’re providing some really novel information,” Dr. Hermann said. 

He added that terms used in the dementia world such as MCI and frank dementia are somewhat foreign to epileptologists. In addition, interventions to delay, treat, or prevent cognitive decline such as exercise, diet, social activity, and mental stimulation that are regularly discussed by dementia experts are underrepresented in the epilepsy world.

“The things they talk about in memory clinics in the aging world almost routinely have not penetrated to the epilepsy clinics for aging individuals and for the epilepsy community in general.”

The study used the Montreal Cognitive Assessment to identify cognitive decline. “It would be nice to see how these people look with traditional neuropsychological tests,” said Dr. Hermann.

He added that information on the impact of epilepsy on different MCI phenotypes, for example, pure memory impairment subtype; pure nonmemory subtype; and multiple domain subtype, would also be useful.

The study was supported by the AES and the Alzheimer’s Association. 

Dr. Zawar and Dr. Hermann report no relevant disclosures.

A version of this article appeared on Medscape.com.

ORLANDO — People with epilepsy are more likely to decline cognitively compared with those without epilepsy, new research suggests.

Results of the large, longitudinal study show that seizures predicted earlier conversion time from normal cognition to mild cognitive impairment (MCI) but were not associated with conversion from MCI to dementia.

“Modifiable cardiovascular risk factors such as hypertension and diabetes need to be treated more aggressively because they can impact cognition, but epilepsy is another risk factor that needs to be treated in a timely fashion because it appears to be also associated with cognitive impairment,” said study investigator Ifrah Zawar MD, assistant professor, Department of Neurology, University of Virginia in Charlottesville.

The study (abstract #2.172) was presented on December 2 at the American Epilepsy Society annual meeting.
 

An Understudied Issue

Comorbid seizures occur in up to 64% of those with dementia, and patients with dementia and epilepsy have a more aggressive disease course, faster cognitive decline, and more severe neuronal loss, Dr. Zawar told Medscape Medical News.

But the impact of seizures on the conversion of cognitively healthy to MCI and from MCI to dementia, after accounting for cardiovascular risk factors, has not been well studied.

Researchers analyzed longitudinal data of 13,726 patients, mean age about 70 years, who were cognitively healthy or had mild cognitive impairment (MCI). Participants were recruited from 39 Alzheimer’s Disease (AD) centers in the United States from 2005 to 2021. 

Investigators categorized participants into three groups: active (having had seizures in the past year and/or requiring active treatment; N = 118), resolved (not on any treatment for the past year and not having seizures; N = 226), and no seizures (never having had seizures; N = 13,382).

The primary outcome was conversion from cognitively healthy to MCI/dementia and from MCI to dementia in those with and without active epilepsy and resolved epilepsy.

Factors associated with conversion from cognitively healthy to MCI among those with current or active epilepsy included older age (P <.001 for ages 60-80 years and P =.002 for age 80 years or older vs younger than 60 years), male sex (P <.001), lower education (P <.001), hypertension (P <.001), and diabetes (P <.001).

The hazard ratio (HR) for earlier conversion from healthy to worse cognition among those with active epilepsy was 1.76 (95% CI, 1.38-2.24; P <.001), even after accounting for risk factors.

Kaplan-Meier curves showed that the median time to convert from healthy cognition to MCI among people with active epilepsy was about 5 years compared with about 9 years for those with resolved epilepsy and 10.5 years for those without epilepsy.

The story was similar for faster conversion from MCI to dementia. Compared with having no epilepsy, the HR for faster conversion for active epilepsy was 1.44 (95% CI, 1.20-1.73; P <.001).

In addition, the median time to conversion from MCI to dementia was about 3 years for those with active epilepsy compared with about 5 years for those with resolved epilepsy and about 5 years for those without epilepsy.

“It’s important for physicians to understand that uncontrolled epilepsy or active epilepsy is going to impact patients’ cognition adversely, which in itself is associated with increased comorbidity and mortality,” said Dr. Zawar.

The mechanism driving the acceleration to worse cognition in people with epilepsy is “complicated and involves a multitude of factors,” she said.

The researchers did not specifically investigate how use of antiseizure medications correlated with cognitive outcomes, but Dr. Zawar believes that “epilepsy in itself impacts cognition.”

The researchers also didn’t have EEG data for study participants who were recruited from Alzheimer’s disease centers where EEGs aren’t routinely carried out, so such data for many patients may not necessarily exist, said Dr. Zawar.
 

Important Research

Commenting for this news organization, Bruce Hermann, PhD, professor emeritus, Department of Neurology, University of Wisconsin School of Medicine and Public Health,  said that the study is important because of the, “tremendous interest and concern about aging with epilepsy.”

“We want to know how people with chronic epilepsy age cognitively and what’s the cognitive course of those who have late onset epilepsy, particularly those with unknown etiology,” he added. 

Dr. Hermann noted that much of the research in this area has been relatively small and single-center investigations. 

“These larger-scale investigations from outside the epilepsy community are so important because they have data on large numbers of subjects, they have cognitive data, and follow-ups over long periods of time, and they’re providing some really novel information,” Dr. Hermann said. 

He added that terms used in the dementia world such as MCI and frank dementia are somewhat foreign to epileptologists. In addition, interventions to delay, treat, or prevent cognitive decline such as exercise, diet, social activity, and mental stimulation that are regularly discussed by dementia experts are underrepresented in the epilepsy world.

“The things they talk about in memory clinics in the aging world almost routinely have not penetrated to the epilepsy clinics for aging individuals and for the epilepsy community in general.”

The study used the Montreal Cognitive Assessment to identify cognitive decline. “It would be nice to see how these people look with traditional neuropsychological tests,” said Dr. Hermann.

He added that information on the impact of epilepsy on different MCI phenotypes, for example, pure memory impairment subtype; pure nonmemory subtype; and multiple domain subtype, would also be useful.

The study was supported by the AES and the Alzheimer’s Association. 

Dr. Zawar and Dr. Hermann report no relevant disclosures.

A version of this article appeared on Medscape.com.

ORLANDO — People with epilepsy are more likely to decline cognitively compared with those without epilepsy, new research suggests.

Results of the large, longitudinal study show that seizures predicted earlier conversion time from normal cognition to mild cognitive impairment (MCI) but were not associated with conversion from MCI to dementia.

“Modifiable cardiovascular risk factors such as hypertension and diabetes need to be treated more aggressively because they can impact cognition, but epilepsy is another risk factor that needs to be treated in a timely fashion because it appears to be also associated with cognitive impairment,” said study investigator Ifrah Zawar MD, assistant professor, Department of Neurology, University of Virginia in Charlottesville.

The study (abstract #2.172) was presented on December 2 at the American Epilepsy Society annual meeting.
 

An Understudied Issue

Comorbid seizures occur in up to 64% of those with dementia, and patients with dementia and epilepsy have a more aggressive disease course, faster cognitive decline, and more severe neuronal loss, Dr. Zawar told Medscape Medical News.

But the impact of seizures on the conversion of cognitively healthy to MCI and from MCI to dementia, after accounting for cardiovascular risk factors, has not been well studied.

Researchers analyzed longitudinal data of 13,726 patients, mean age about 70 years, who were cognitively healthy or had mild cognitive impairment (MCI). Participants were recruited from 39 Alzheimer’s Disease (AD) centers in the United States from 2005 to 2021. 

Investigators categorized participants into three groups: active (having had seizures in the past year and/or requiring active treatment; N = 118), resolved (not on any treatment for the past year and not having seizures; N = 226), and no seizures (never having had seizures; N = 13,382).

The primary outcome was conversion from cognitively healthy to MCI/dementia and from MCI to dementia in those with and without active epilepsy and resolved epilepsy.

Factors associated with conversion from cognitively healthy to MCI among those with current or active epilepsy included older age (P <.001 for ages 60-80 years and P =.002 for age 80 years or older vs younger than 60 years), male sex (P <.001), lower education (P <.001), hypertension (P <.001), and diabetes (P <.001).

The hazard ratio (HR) for earlier conversion from healthy to worse cognition among those with active epilepsy was 1.76 (95% CI, 1.38-2.24; P <.001), even after accounting for risk factors.

Kaplan-Meier curves showed that the median time to convert from healthy cognition to MCI among people with active epilepsy was about 5 years compared with about 9 years for those with resolved epilepsy and 10.5 years for those without epilepsy.

The story was similar for faster conversion from MCI to dementia. Compared with having no epilepsy, the HR for faster conversion for active epilepsy was 1.44 (95% CI, 1.20-1.73; P <.001).

In addition, the median time to conversion from MCI to dementia was about 3 years for those with active epilepsy compared with about 5 years for those with resolved epilepsy and about 5 years for those without epilepsy.

“It’s important for physicians to understand that uncontrolled epilepsy or active epilepsy is going to impact patients’ cognition adversely, which in itself is associated with increased comorbidity and mortality,” said Dr. Zawar.

The mechanism driving the acceleration to worse cognition in people with epilepsy is “complicated and involves a multitude of factors,” she said.

The researchers did not specifically investigate how use of antiseizure medications correlated with cognitive outcomes, but Dr. Zawar believes that “epilepsy in itself impacts cognition.”

The researchers also didn’t have EEG data for study participants who were recruited from Alzheimer’s disease centers where EEGs aren’t routinely carried out, so such data for many patients may not necessarily exist, said Dr. Zawar.
 

Important Research

Commenting for this news organization, Bruce Hermann, PhD, professor emeritus, Department of Neurology, University of Wisconsin School of Medicine and Public Health,  said that the study is important because of the, “tremendous interest and concern about aging with epilepsy.”

“We want to know how people with chronic epilepsy age cognitively and what’s the cognitive course of those who have late onset epilepsy, particularly those with unknown etiology,” he added. 

Dr. Hermann noted that much of the research in this area has been relatively small and single-center investigations. 

“These larger-scale investigations from outside the epilepsy community are so important because they have data on large numbers of subjects, they have cognitive data, and follow-ups over long periods of time, and they’re providing some really novel information,” Dr. Hermann said. 

He added that terms used in the dementia world such as MCI and frank dementia are somewhat foreign to epileptologists. In addition, interventions to delay, treat, or prevent cognitive decline such as exercise, diet, social activity, and mental stimulation that are regularly discussed by dementia experts are underrepresented in the epilepsy world.

“The things they talk about in memory clinics in the aging world almost routinely have not penetrated to the epilepsy clinics for aging individuals and for the epilepsy community in general.”

The study used the Montreal Cognitive Assessment to identify cognitive decline. “It would be nice to see how these people look with traditional neuropsychological tests,” said Dr. Hermann.

He added that information on the impact of epilepsy on different MCI phenotypes, for example, pure memory impairment subtype; pure nonmemory subtype; and multiple domain subtype, would also be useful.

The study was supported by the AES and the Alzheimer’s Association. 

Dr. Zawar and Dr. Hermann report no relevant disclosures.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Imposing a new prior authorization requirement increased the likelihood that older patients with cancer will delay or stop filling their prescription for oral anticancer drugs, a new study showed.

METHODOLOGY:

• Prior authorization requirements, especially in oncology, continue to increase, but how these policies affect patients’ access to care remains less clear.
• Researchers analyzed Medicare Part D claims from 2010 to 2020 to assess the effects of prior authorization changes on prescriptions fills for 1 of 11 oral anticancer drugs.
• The study included 2495 patients filling a prescription for these medications prior to their health plan imposing a new prior authorization policy and 22,641 patients filling prescriptions for the same drugs with no change in prior authorization policy (control).
• Beneficiaries had at least three 30-day fills in the 120 days before the new prior authorization policy was established on January 1 and continued to be enrolled in the same plan 120 days after the policy change.
• The researchers focused on how often patients discontinued their therapy within 120 days following a prior authorization policy change, as well as the time to fill a prescription after this change.

TAKEAWAY:

• Patients subjected to a new prior authorization policy on an established drug had a sevenfold higher likelihood of stopping the drug within 120 days than those who had no change in prior authorization requirements (adjusted odds ratio, 7.1).
• The adjusted probability of discontinuing an oral cancer regimen within 120 days after an index date of January 1 (when most health plan policy changes occur) was 5.8% for those with a new prior authorization policy vs 1.4% for the control group.
• A new prior authorization requirement was also associated with an average 10-day delay to refill the first prescription following the policy change (P < .001).
• The probability of a delay of more than 30 days was 22% after a policy change vs 7% after no policy change.

IN PRACTICE:

“Our results suggest concerns about delayed and foregone care related to prior authorization are warranted,” the authors said. Overall, this study found that “prior authorization wasted time and undermined the policy priorities of access to care and oral anticancer drug adherence for patients who were regular users of a particular medication.”

SOURCE:

The study by Michael Anna Kyle, PhD, RN, and Nancy Keating, MD, MPH, with Harvard Medical School, Boston, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

The study did not look at patients starting new oral anticancer drugs, which may come with more complex prior authorization processes and create more significant access issues. The results are also limited to patients taking 1 of 11 oral anticancer agents in Medicare Part D.

DISCLOSURES:

Funding for the study was provided by the National Cancer Institute. The authors reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Imposing a new prior authorization requirement increased the likelihood that older patients with cancer will delay or stop filling their prescription for oral anticancer drugs, a new study showed.

METHODOLOGY:

• Prior authorization requirements, especially in oncology, continue to increase, but how these policies affect patients’ access to care remains less clear.
• Researchers analyzed Medicare Part D claims from 2010 to 2020 to assess the effects of prior authorization changes on prescriptions fills for 1 of 11 oral anticancer drugs.
• The study included 2495 patients filling a prescription for these medications prior to their health plan imposing a new prior authorization policy and 22,641 patients filling prescriptions for the same drugs with no change in prior authorization policy (control).
• Beneficiaries had at least three 30-day fills in the 120 days before the new prior authorization policy was established on January 1 and continued to be enrolled in the same plan 120 days after the policy change.
• The researchers focused on how often patients discontinued their therapy within 120 days following a prior authorization policy change, as well as the time to fill a prescription after this change.

TAKEAWAY:

• Patients subjected to a new prior authorization policy on an established drug had a sevenfold higher likelihood of stopping the drug within 120 days than those who had no change in prior authorization requirements (adjusted odds ratio, 7.1).
• The adjusted probability of discontinuing an oral cancer regimen within 120 days after an index date of January 1 (when most health plan policy changes occur) was 5.8% for those with a new prior authorization policy vs 1.4% for the control group.
• A new prior authorization requirement was also associated with an average 10-day delay to refill the first prescription following the policy change (P < .001).
• The probability of a delay of more than 30 days was 22% after a policy change vs 7% after no policy change.

IN PRACTICE:

“Our results suggest concerns about delayed and foregone care related to prior authorization are warranted,” the authors said. Overall, this study found that “prior authorization wasted time and undermined the policy priorities of access to care and oral anticancer drug adherence for patients who were regular users of a particular medication.”

SOURCE:

The study by Michael Anna Kyle, PhD, RN, and Nancy Keating, MD, MPH, with Harvard Medical School, Boston, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

The study did not look at patients starting new oral anticancer drugs, which may come with more complex prior authorization processes and create more significant access issues. The results are also limited to patients taking 1 of 11 oral anticancer agents in Medicare Part D.

DISCLOSURES:

Funding for the study was provided by the National Cancer Institute. The authors reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Imposing a new prior authorization requirement increased the likelihood that older patients with cancer will delay or stop filling their prescription for oral anticancer drugs, a new study showed.

METHODOLOGY:

• Prior authorization requirements, especially in oncology, continue to increase, but how these policies affect patients’ access to care remains less clear.
• Researchers analyzed Medicare Part D claims from 2010 to 2020 to assess the effects of prior authorization changes on prescriptions fills for 1 of 11 oral anticancer drugs.
• The study included 2495 patients filling a prescription for these medications prior to their health plan imposing a new prior authorization policy and 22,641 patients filling prescriptions for the same drugs with no change in prior authorization policy (control).
• Beneficiaries had at least three 30-day fills in the 120 days before the new prior authorization policy was established on January 1 and continued to be enrolled in the same plan 120 days after the policy change.
• The researchers focused on how often patients discontinued their therapy within 120 days following a prior authorization policy change, as well as the time to fill a prescription after this change.

TAKEAWAY:

• Patients subjected to a new prior authorization policy on an established drug had a sevenfold higher likelihood of stopping the drug within 120 days than those who had no change in prior authorization requirements (adjusted odds ratio, 7.1).
• The adjusted probability of discontinuing an oral cancer regimen within 120 days after an index date of January 1 (when most health plan policy changes occur) was 5.8% for those with a new prior authorization policy vs 1.4% for the control group.
• A new prior authorization requirement was also associated with an average 10-day delay to refill the first prescription following the policy change (P < .001).
• The probability of a delay of more than 30 days was 22% after a policy change vs 7% after no policy change.

IN PRACTICE:

“Our results suggest concerns about delayed and foregone care related to prior authorization are warranted,” the authors said. Overall, this study found that “prior authorization wasted time and undermined the policy priorities of access to care and oral anticancer drug adherence for patients who were regular users of a particular medication.”

SOURCE:

The study by Michael Anna Kyle, PhD, RN, and Nancy Keating, MD, MPH, with Harvard Medical School, Boston, was published online in the Journal of Clinical Oncology.

LIMITATIONS:

The study did not look at patients starting new oral anticancer drugs, which may come with more complex prior authorization processes and create more significant access issues. The results are also limited to patients taking 1 of 11 oral anticancer agents in Medicare Part D.

DISCLOSURES:

Funding for the study was provided by the National Cancer Institute. The authors reported no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Mark Lewis, MD, saw the pain in his patient’s body. The man’s gastrointestinal tumor had metastasized to his bones. Even breathing had become agonizing.

It was a Friday afternoon. Dr. Lewis could see his patient would struggle to make it through the weekend without some pain relief.

When this happens, “the clock is ticking,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, Utah. “A patient, especially one with more advanced disease, only has so much time to wait for care.”

Dr. Lewis sent in an electronic request for an opioid prescription to help ease his patient’s pain through the weekend. Once the prescription had gone through, Dr. Lewis told his patient the medication should be ready to pick up at his local pharmacy.

Dr. Lewis left work that Friday feeling a little lighter, knowing the pain medication would help his patient over the weekend.

Moments after walking into the clinic on Monday morning, Dr. Lewis received an unexpected message: “Your patient is in the hospital.”

The events of the weekend soon unfolded.

Dr. Lewis learned that when his patient went to the pharmacy to pick up his pain medication, the pharmacist told him the prescription required prior authorization.

The patient left the pharmacy empty-handed. Hours later, he was in the emergency room (ER) in extreme pain — the exact situation Dr. Lewis had been trying to avoid.

Dr. Lewis felt a sense of powerlessness in that moment.

“I had been left in the dark,” he said. The oncologist-patient relationship is predicated on trust and “that trust is eroded when I can’t give my patients the care they need,” he explained. “I can’t stand overpromising and underdelivering to them.”

Dr. Lewis had received no communication from the insurer that the prescription required prior authorization, no red flag that the request had been denied, and no notification to call the insurer.

Although physicians may need to tread carefully when prescribing opioids over the long term, “this was simply a prescription for 2-3 days of opioids for the exact patient who the drugs were developed to benefit,” Dr. Lewis said. But instead, “he ended up in ER with a pain crisis.”

Prior authorization delays like this often mean patients pay the price.

“These delays are not trivial,” Dr. Lewis said.

A recent study, presented at the ASCO Quality Care Symposium in October, found that among 3304 supportive care prescriptions requiring prior authorization, insurance companies denied 8% of requests, with final denials taking as long as 78 days. Among approved prescriptions, about 40% happened on the same day, while the remaining took anywhere from 1 to 54 days.

Denying or delaying necessary and cost-effective care, even briefly, can harm patients and lead to higher costs. A 2022 survey from the American Medical Association found that instead of reducing low-value care as insurance companies claim, prior authorization often leads to higher overall use of healthcare resources. More specifically, almost half of physicians surveyed said that prior authorization led to an ER visit or need for immediate care.

In this patient’s case, filling the opioid prescription that Friday would have cost no more than $300, possibly as little as $30. The ER visit to manage the patient’s pain crisis costs thousands.

The major issue overall, Dr. Lewis said, is the disconnect between the time spent waiting for prior authorization approvals and the necessity of these treatments. Dr. Lewis says even standard chemotherapy often requires prior authorization.

“The currency we all share is time,” Dr. Lewis said. “But it often feels like there’s very little urgency on insurance company side to approve a treatment, which places a heavy weight on patients and physicians.”

“It just shouldn’t be this hard,” he said.

A version of this article appeared on Medscape.com as part of the Gatekeepers of Care series on issues oncologists and people with cancer face navigating health insurance company requirements. Read more about the series here. Please email [email protected] to share experiences with prior authorization or other challenges receiving care.

Mark Lewis, MD, saw the pain in his patient’s body. The man’s gastrointestinal tumor had metastasized to his bones. Even breathing had become agonizing.

It was a Friday afternoon. Dr. Lewis could see his patient would struggle to make it through the weekend without some pain relief.

When this happens, “the clock is ticking,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, Utah. “A patient, especially one with more advanced disease, only has so much time to wait for care.”

Dr. Lewis sent in an electronic request for an opioid prescription to help ease his patient’s pain through the weekend. Once the prescription had gone through, Dr. Lewis told his patient the medication should be ready to pick up at his local pharmacy.

Dr. Lewis left work that Friday feeling a little lighter, knowing the pain medication would help his patient over the weekend.

Moments after walking into the clinic on Monday morning, Dr. Lewis received an unexpected message: “Your patient is in the hospital.”

The events of the weekend soon unfolded.

Dr. Lewis learned that when his patient went to the pharmacy to pick up his pain medication, the pharmacist told him the prescription required prior authorization.

The patient left the pharmacy empty-handed. Hours later, he was in the emergency room (ER) in extreme pain — the exact situation Dr. Lewis had been trying to avoid.

Dr. Lewis felt a sense of powerlessness in that moment.

“I had been left in the dark,” he said. The oncologist-patient relationship is predicated on trust and “that trust is eroded when I can’t give my patients the care they need,” he explained. “I can’t stand overpromising and underdelivering to them.”

Dr. Lewis had received no communication from the insurer that the prescription required prior authorization, no red flag that the request had been denied, and no notification to call the insurer.

Although physicians may need to tread carefully when prescribing opioids over the long term, “this was simply a prescription for 2-3 days of opioids for the exact patient who the drugs were developed to benefit,” Dr. Lewis said. But instead, “he ended up in ER with a pain crisis.”

Prior authorization delays like this often mean patients pay the price.

“These delays are not trivial,” Dr. Lewis said.

A recent study, presented at the ASCO Quality Care Symposium in October, found that among 3304 supportive care prescriptions requiring prior authorization, insurance companies denied 8% of requests, with final denials taking as long as 78 days. Among approved prescriptions, about 40% happened on the same day, while the remaining took anywhere from 1 to 54 days.

Denying or delaying necessary and cost-effective care, even briefly, can harm patients and lead to higher costs. A 2022 survey from the American Medical Association found that instead of reducing low-value care as insurance companies claim, prior authorization often leads to higher overall use of healthcare resources. More specifically, almost half of physicians surveyed said that prior authorization led to an ER visit or need for immediate care.

In this patient’s case, filling the opioid prescription that Friday would have cost no more than $300, possibly as little as $30. The ER visit to manage the patient’s pain crisis costs thousands.

The major issue overall, Dr. Lewis said, is the disconnect between the time spent waiting for prior authorization approvals and the necessity of these treatments. Dr. Lewis says even standard chemotherapy often requires prior authorization.

“The currency we all share is time,” Dr. Lewis said. “But it often feels like there’s very little urgency on insurance company side to approve a treatment, which places a heavy weight on patients and physicians.”

“It just shouldn’t be this hard,” he said.

A version of this article appeared on Medscape.com as part of the Gatekeepers of Care series on issues oncologists and people with cancer face navigating health insurance company requirements. Read more about the series here. Please email [email protected] to share experiences with prior authorization or other challenges receiving care.

Mark Lewis, MD, saw the pain in his patient’s body. The man’s gastrointestinal tumor had metastasized to his bones. Even breathing had become agonizing.

It was a Friday afternoon. Dr. Lewis could see his patient would struggle to make it through the weekend without some pain relief.

When this happens, “the clock is ticking,” said Dr. Lewis, director of gastrointestinal oncology at Intermountain Health in Salt Lake City, Utah. “A patient, especially one with more advanced disease, only has so much time to wait for care.”

Dr. Lewis sent in an electronic request for an opioid prescription to help ease his patient’s pain through the weekend. Once the prescription had gone through, Dr. Lewis told his patient the medication should be ready to pick up at his local pharmacy.

Dr. Lewis left work that Friday feeling a little lighter, knowing the pain medication would help his patient over the weekend.

Moments after walking into the clinic on Monday morning, Dr. Lewis received an unexpected message: “Your patient is in the hospital.”

The events of the weekend soon unfolded.

Dr. Lewis learned that when his patient went to the pharmacy to pick up his pain medication, the pharmacist told him the prescription required prior authorization.

The patient left the pharmacy empty-handed. Hours later, he was in the emergency room (ER) in extreme pain — the exact situation Dr. Lewis had been trying to avoid.

Dr. Lewis felt a sense of powerlessness in that moment.

“I had been left in the dark,” he said. The oncologist-patient relationship is predicated on trust and “that trust is eroded when I can’t give my patients the care they need,” he explained. “I can’t stand overpromising and underdelivering to them.”

Dr. Lewis had received no communication from the insurer that the prescription required prior authorization, no red flag that the request had been denied, and no notification to call the insurer.

Although physicians may need to tread carefully when prescribing opioids over the long term, “this was simply a prescription for 2-3 days of opioids for the exact patient who the drugs were developed to benefit,” Dr. Lewis said. But instead, “he ended up in ER with a pain crisis.”

Prior authorization delays like this often mean patients pay the price.

“These delays are not trivial,” Dr. Lewis said.

A recent study, presented at the ASCO Quality Care Symposium in October, found that among 3304 supportive care prescriptions requiring prior authorization, insurance companies denied 8% of requests, with final denials taking as long as 78 days. Among approved prescriptions, about 40% happened on the same day, while the remaining took anywhere from 1 to 54 days.

Denying or delaying necessary and cost-effective care, even briefly, can harm patients and lead to higher costs. A 2022 survey from the American Medical Association found that instead of reducing low-value care as insurance companies claim, prior authorization often leads to higher overall use of healthcare resources. More specifically, almost half of physicians surveyed said that prior authorization led to an ER visit or need for immediate care.

In this patient’s case, filling the opioid prescription that Friday would have cost no more than $300, possibly as little as $30. The ER visit to manage the patient’s pain crisis costs thousands.

The major issue overall, Dr. Lewis said, is the disconnect between the time spent waiting for prior authorization approvals and the necessity of these treatments. Dr. Lewis says even standard chemotherapy often requires prior authorization.

“The currency we all share is time,” Dr. Lewis said. “But it often feels like there’s very little urgency on insurance company side to approve a treatment, which places a heavy weight on patients and physicians.”

“It just shouldn’t be this hard,” he said.

A version of this article appeared on Medscape.com as part of the Gatekeepers of Care series on issues oncologists and people with cancer face navigating health insurance company requirements. Read more about the series here. Please email [email protected] to share experiences with prior authorization or other challenges receiving care.

Rapid surges in insulin following a meal are associated with favorable long-term cardiometabolic benefits, including improvements in beta cell function and a lower risk for the development of prediabetes or diabetes, contrary to some concerns of the surges being indicative of more negative effects.

“There are practitioners who subscribe to this notion of higher insulin levels being a bad thing, and sometimes are making recommendations to patients to limit their insulin fluctuations after the meal,” said first author Ravi Retnakaran, MD, an endocrinologist and Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at the Leadership Sinai Centre for Diabetes at Mount Sinai Hospital, Toronto, Ontario, in a press statement.

“But it’s not that simple,” he said. “We observed that a robust post-challenge insulin secretory response, once adjusted for glucose levels, is only associated with beneficial metabolic effects.”

The findings were published on December 13, 2023, in eClinicalMedicine, part of The Lancet Discovery Science.

Insulin levels increase after food consumption in the normal management of blood glucose; however, some research has suggested that more rapid spikes in insulin, especially after a high-carbohydrate meal, are linked to an anabolic state contributing to weight gain and insulin resistance.

As public awareness of those reports has grown, “patients are coming in concerned about the possibility of their insulin levels being high, and there is confusion about the physiology of these effects,” Dr. Retnakaran told this news organization. 

However, other studies have shown that the effects of insulin surges are important relative to baseline factors, including ambient glycemia and, specifically, baseline glucose levels prior to a meal.

Therefore, a more appropriate assessment is to use a corrected insulin response, measuring insulin secretion at 30 minutes after an oral glucose challenge, in relation to baseline glucose levels, research has suggested.

To investigate the issue in a longitudinal context, Dr. Retnakaran and colleagues conducted a prospective cohort study of 306 pregnant women representing a full range of glucose tolerance, who were enrolled at a hospital in Toronto between October 2003 and March 2014.

The women received comprehensive cardiometabolic testing, including oral glucose tolerance tests at 1-year, 3-year, and 5-year postpartum, and their baseline post-challenge insulinemia was established using corrected insulin response at 1 year.

Over 4 years of follow-up, a progressive worsening of cardiometabolic factors was associated with higher tertiles of corrected insulin responses at baseline, including waist circumference (P = .016), high-density lipoprotein (P = .018), C-reactive protein (CRP; P = .006), and insulin sensitivity (P < .001).

However, those trends were also associated with progressively improved beta cell function (P < .001).

After adjustment in the longitudinal analysis for the clinical risk factors for diabetes, including age, ethnicity, family history of diabetes, and body mass index (BMI) at 1 year, a higher corrected insulin response tertile at baseline was independently associated with improved Insulin Secretion-Sensitivity Index-2 and insulinogenic index/insulin resistance index (IGI/HOMA-IR), as well as lower glycemia, as observed on fasting and 2-hour glucose at 3 years and 5 years (all P < .001).

The insulin response was meanwhile not associated with BMI, waist, lipids, CRP, or insulin sensitivity or resistance.

Importantly, the highest corrected insulin response tertile at 1-year postpartum was also significantly associated with a lower risk for prediabetes or diabetes than the lowest tertile at 3 years (adjusted OR [aOR], 0.19) as well as 5 years (aOR, 0.18).

“The real question in my mind was whether we had the statistical power to be able to demonstrate a longitudinal beneficial effect on glucose regulation, but we did,” Dr. Retnakaran told this news organization. “The results show lower prediabetes and diabetes among people who had the most robust postprandial insulin excursion at 1-year postpartum.”

While the unadjusted analyses at baseline showed adverse as well as favorable outcomes, “adjusted longitudinal analyses revealed consistent independent associations of higher complete insulin response with better beta cell function, lower glycemia, and lower risk of prediabetes or diabetes in the years thereafter,” the authors reported.

“This evidence should help push back concern around the postprandial insulin spike,” Dr. Retnakaran said.

Commenting on the study, James D. Johnson, PhD, a professor of cellular and physiological sciences and director of the Life Sciences Institute at the University of British Columbia, Canada, noted that “it is already well-known that the loss of postprandial first phase insulin secretion can be a key and early defect in the transition to prediabetes and type 2 diabetes. That is not new, but the confirmatory data are welcome,” he told this news organization.

However, with other data linking high insulin with adiposity and insulin resistance, “the nuance and subtleties are critical for us to understand the directions of the causality,” he said.

“It is quite possible that both of these models are true at different life stages and/or in different people. There may be more than one pathway to diabetes. This is the nature of science and progress.”

A key caveat is that with a specific cohort of pregnant women, the question remains of the generalizability to men and to those younger or older than childbearing age.

Nevertheless, “I think this is an interesting and important study,” Dr. Johnson said. “More data on this topic is always welcome, but I am not sure this will be the final say in this debate.”

The authors and Dr. Johnson had no disclosures to report.

A version of this article appeared on Medscape.com.

Rapid surges in insulin following a meal are associated with favorable long-term cardiometabolic benefits, including improvements in beta cell function and a lower risk for the development of prediabetes or diabetes, contrary to some concerns of the surges being indicative of more negative effects.

“There are practitioners who subscribe to this notion of higher insulin levels being a bad thing, and sometimes are making recommendations to patients to limit their insulin fluctuations after the meal,” said first author Ravi Retnakaran, MD, an endocrinologist and Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at the Leadership Sinai Centre for Diabetes at Mount Sinai Hospital, Toronto, Ontario, in a press statement.

“But it’s not that simple,” he said. “We observed that a robust post-challenge insulin secretory response, once adjusted for glucose levels, is only associated with beneficial metabolic effects.”

The findings were published on December 13, 2023, in eClinicalMedicine, part of The Lancet Discovery Science.

Insulin levels increase after food consumption in the normal management of blood glucose; however, some research has suggested that more rapid spikes in insulin, especially after a high-carbohydrate meal, are linked to an anabolic state contributing to weight gain and insulin resistance.

As public awareness of those reports has grown, “patients are coming in concerned about the possibility of their insulin levels being high, and there is confusion about the physiology of these effects,” Dr. Retnakaran told this news organization. 

However, other studies have shown that the effects of insulin surges are important relative to baseline factors, including ambient glycemia and, specifically, baseline glucose levels prior to a meal.

Therefore, a more appropriate assessment is to use a corrected insulin response, measuring insulin secretion at 30 minutes after an oral glucose challenge, in relation to baseline glucose levels, research has suggested.

To investigate the issue in a longitudinal context, Dr. Retnakaran and colleagues conducted a prospective cohort study of 306 pregnant women representing a full range of glucose tolerance, who were enrolled at a hospital in Toronto between October 2003 and March 2014.

The women received comprehensive cardiometabolic testing, including oral glucose tolerance tests at 1-year, 3-year, and 5-year postpartum, and their baseline post-challenge insulinemia was established using corrected insulin response at 1 year.

Over 4 years of follow-up, a progressive worsening of cardiometabolic factors was associated with higher tertiles of corrected insulin responses at baseline, including waist circumference (P = .016), high-density lipoprotein (P = .018), C-reactive protein (CRP; P = .006), and insulin sensitivity (P < .001).

However, those trends were also associated with progressively improved beta cell function (P < .001).

After adjustment in the longitudinal analysis for the clinical risk factors for diabetes, including age, ethnicity, family history of diabetes, and body mass index (BMI) at 1 year, a higher corrected insulin response tertile at baseline was independently associated with improved Insulin Secretion-Sensitivity Index-2 and insulinogenic index/insulin resistance index (IGI/HOMA-IR), as well as lower glycemia, as observed on fasting and 2-hour glucose at 3 years and 5 years (all P < .001).

The insulin response was meanwhile not associated with BMI, waist, lipids, CRP, or insulin sensitivity or resistance.

Importantly, the highest corrected insulin response tertile at 1-year postpartum was also significantly associated with a lower risk for prediabetes or diabetes than the lowest tertile at 3 years (adjusted OR [aOR], 0.19) as well as 5 years (aOR, 0.18).

“The real question in my mind was whether we had the statistical power to be able to demonstrate a longitudinal beneficial effect on glucose regulation, but we did,” Dr. Retnakaran told this news organization. “The results show lower prediabetes and diabetes among people who had the most robust postprandial insulin excursion at 1-year postpartum.”

While the unadjusted analyses at baseline showed adverse as well as favorable outcomes, “adjusted longitudinal analyses revealed consistent independent associations of higher complete insulin response with better beta cell function, lower glycemia, and lower risk of prediabetes or diabetes in the years thereafter,” the authors reported.

“This evidence should help push back concern around the postprandial insulin spike,” Dr. Retnakaran said.

Commenting on the study, James D. Johnson, PhD, a professor of cellular and physiological sciences and director of the Life Sciences Institute at the University of British Columbia, Canada, noted that “it is already well-known that the loss of postprandial first phase insulin secretion can be a key and early defect in the transition to prediabetes and type 2 diabetes. That is not new, but the confirmatory data are welcome,” he told this news organization.

However, with other data linking high insulin with adiposity and insulin resistance, “the nuance and subtleties are critical for us to understand the directions of the causality,” he said.

“It is quite possible that both of these models are true at different life stages and/or in different people. There may be more than one pathway to diabetes. This is the nature of science and progress.”

A key caveat is that with a specific cohort of pregnant women, the question remains of the generalizability to men and to those younger or older than childbearing age.

Nevertheless, “I think this is an interesting and important study,” Dr. Johnson said. “More data on this topic is always welcome, but I am not sure this will be the final say in this debate.”

The authors and Dr. Johnson had no disclosures to report.

A version of this article appeared on Medscape.com.

Rapid surges in insulin following a meal are associated with favorable long-term cardiometabolic benefits, including improvements in beta cell function and a lower risk for the development of prediabetes or diabetes, contrary to some concerns of the surges being indicative of more negative effects.

“There are practitioners who subscribe to this notion of higher insulin levels being a bad thing, and sometimes are making recommendations to patients to limit their insulin fluctuations after the meal,” said first author Ravi Retnakaran, MD, an endocrinologist and Boehringer Ingelheim Chair in Beta-cell Preservation, Function and Regeneration at the Leadership Sinai Centre for Diabetes at Mount Sinai Hospital, Toronto, Ontario, in a press statement.

“But it’s not that simple,” he said. “We observed that a robust post-challenge insulin secretory response, once adjusted for glucose levels, is only associated with beneficial metabolic effects.”

The findings were published on December 13, 2023, in eClinicalMedicine, part of The Lancet Discovery Science.

Insulin levels increase after food consumption in the normal management of blood glucose; however, some research has suggested that more rapid spikes in insulin, especially after a high-carbohydrate meal, are linked to an anabolic state contributing to weight gain and insulin resistance.

As public awareness of those reports has grown, “patients are coming in concerned about the possibility of their insulin levels being high, and there is confusion about the physiology of these effects,” Dr. Retnakaran told this news organization. 

However, other studies have shown that the effects of insulin surges are important relative to baseline factors, including ambient glycemia and, specifically, baseline glucose levels prior to a meal.

Therefore, a more appropriate assessment is to use a corrected insulin response, measuring insulin secretion at 30 minutes after an oral glucose challenge, in relation to baseline glucose levels, research has suggested.

To investigate the issue in a longitudinal context, Dr. Retnakaran and colleagues conducted a prospective cohort study of 306 pregnant women representing a full range of glucose tolerance, who were enrolled at a hospital in Toronto between October 2003 and March 2014.

The women received comprehensive cardiometabolic testing, including oral glucose tolerance tests at 1-year, 3-year, and 5-year postpartum, and their baseline post-challenge insulinemia was established using corrected insulin response at 1 year.

Over 4 years of follow-up, a progressive worsening of cardiometabolic factors was associated with higher tertiles of corrected insulin responses at baseline, including waist circumference (P = .016), high-density lipoprotein (P = .018), C-reactive protein (CRP; P = .006), and insulin sensitivity (P < .001).

However, those trends were also associated with progressively improved beta cell function (P < .001).

After adjustment in the longitudinal analysis for the clinical risk factors for diabetes, including age, ethnicity, family history of diabetes, and body mass index (BMI) at 1 year, a higher corrected insulin response tertile at baseline was independently associated with improved Insulin Secretion-Sensitivity Index-2 and insulinogenic index/insulin resistance index (IGI/HOMA-IR), as well as lower glycemia, as observed on fasting and 2-hour glucose at 3 years and 5 years (all P < .001).

The insulin response was meanwhile not associated with BMI, waist, lipids, CRP, or insulin sensitivity or resistance.

Importantly, the highest corrected insulin response tertile at 1-year postpartum was also significantly associated with a lower risk for prediabetes or diabetes than the lowest tertile at 3 years (adjusted OR [aOR], 0.19) as well as 5 years (aOR, 0.18).

“The real question in my mind was whether we had the statistical power to be able to demonstrate a longitudinal beneficial effect on glucose regulation, but we did,” Dr. Retnakaran told this news organization. “The results show lower prediabetes and diabetes among people who had the most robust postprandial insulin excursion at 1-year postpartum.”

While the unadjusted analyses at baseline showed adverse as well as favorable outcomes, “adjusted longitudinal analyses revealed consistent independent associations of higher complete insulin response with better beta cell function, lower glycemia, and lower risk of prediabetes or diabetes in the years thereafter,” the authors reported.

“This evidence should help push back concern around the postprandial insulin spike,” Dr. Retnakaran said.

Commenting on the study, James D. Johnson, PhD, a professor of cellular and physiological sciences and director of the Life Sciences Institute at the University of British Columbia, Canada, noted that “it is already well-known that the loss of postprandial first phase insulin secretion can be a key and early defect in the transition to prediabetes and type 2 diabetes. That is not new, but the confirmatory data are welcome,” he told this news organization.

However, with other data linking high insulin with adiposity and insulin resistance, “the nuance and subtleties are critical for us to understand the directions of the causality,” he said.

“It is quite possible that both of these models are true at different life stages and/or in different people. There may be more than one pathway to diabetes. This is the nature of science and progress.”

A key caveat is that with a specific cohort of pregnant women, the question remains of the generalizability to men and to those younger or older than childbearing age.

Nevertheless, “I think this is an interesting and important study,” Dr. Johnson said. “More data on this topic is always welcome, but I am not sure this will be the final say in this debate.”

The authors and Dr. Johnson had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

The time arrived at peak blood pressure (BP) velocity (TAPV) was significantly earlier in children with moderate to severe (MS) obstructive sleep apnea (OSA) than in controls.

METHODOLOGY:

• The researchers compared 24-hour circadian BP in children with OSA and controls to examine the impact of OSA on circadian BP.
• The study population included 219 children aged 5-14 years: 52 with mild OSA, 50 with MS OSA, and 117 controls.
• Participants underwent 24-hour BP monitoring and actigraphy; models included the times of BP peaks and TAPV.

TAKEAWAY:

• Children with MS OSA had a TAPV for diastolic BP in the morning, an average of 51 minutes earlier than controls (P < .001).
• Evening TAPV was significantly earlier in the children with MS OSA than in controls for both systolic BP (SBP) and diastolic BP (DBP) (95 min, P < .001 and 28 min, P = .028, respectively).
• Midday SBP and DBP velocity nadirs were significantly earlier in the children with MS OSA than in controls (57 min, P < .001 and 38 min, P < .01, respectively).
• Overall, children with MS OSA reached most BP values significantly earlier than controls, and both SBP and DBP were significantly elevated in the MS OSA group compared with the control group.

IN PRACTICE:

“The findings provide an essential puzzle piece in our understanding of the cardiovascular effects of OSA in children,” wrote the authors of an accompanying editorial.

SOURCE:

The lead author of the study was Md Tareq Ferdous Khan, MD, of the University of Cincinnati, Cincinnati, Ohio; the authors of the accompanying editorial were Kate Ching-Ching Chan, MD, and Albert Martin Li, MD, of the Chinese University of Hong Kong, China. The study was published online in the journal Sleep on December 13, 2023, along with the accompanying editorial.

LIMITATIONS:

More research is needed to investigate the potential mechanisms of action, optimize methodology, and investigate circadian biology via actigraphy and biomarkers, the authors of an accompanying editorial wrote.

DISCLOSURES:

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The time arrived at peak blood pressure (BP) velocity (TAPV) was significantly earlier in children with moderate to severe (MS) obstructive sleep apnea (OSA) than in controls.

METHODOLOGY:

• The researchers compared 24-hour circadian BP in children with OSA and controls to examine the impact of OSA on circadian BP.
• The study population included 219 children aged 5-14 years: 52 with mild OSA, 50 with MS OSA, and 117 controls.
• Participants underwent 24-hour BP monitoring and actigraphy; models included the times of BP peaks and TAPV.

TAKEAWAY:

• Children with MS OSA had a TAPV for diastolic BP in the morning, an average of 51 minutes earlier than controls (P < .001).
• Evening TAPV was significantly earlier in the children with MS OSA than in controls for both systolic BP (SBP) and diastolic BP (DBP) (95 min, P < .001 and 28 min, P = .028, respectively).
• Midday SBP and DBP velocity nadirs were significantly earlier in the children with MS OSA than in controls (57 min, P < .001 and 38 min, P < .01, respectively).
• Overall, children with MS OSA reached most BP values significantly earlier than controls, and both SBP and DBP were significantly elevated in the MS OSA group compared with the control group.

IN PRACTICE:

“The findings provide an essential puzzle piece in our understanding of the cardiovascular effects of OSA in children,” wrote the authors of an accompanying editorial.

SOURCE:

The lead author of the study was Md Tareq Ferdous Khan, MD, of the University of Cincinnati, Cincinnati, Ohio; the authors of the accompanying editorial were Kate Ching-Ching Chan, MD, and Albert Martin Li, MD, of the Chinese University of Hong Kong, China. The study was published online in the journal Sleep on December 13, 2023, along with the accompanying editorial.

LIMITATIONS:

More research is needed to investigate the potential mechanisms of action, optimize methodology, and investigate circadian biology via actigraphy and biomarkers, the authors of an accompanying editorial wrote.

DISCLOSURES:

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

The time arrived at peak blood pressure (BP) velocity (TAPV) was significantly earlier in children with moderate to severe (MS) obstructive sleep apnea (OSA) than in controls.

METHODOLOGY:

• The researchers compared 24-hour circadian BP in children with OSA and controls to examine the impact of OSA on circadian BP.
• The study population included 219 children aged 5-14 years: 52 with mild OSA, 50 with MS OSA, and 117 controls.
• Participants underwent 24-hour BP monitoring and actigraphy; models included the times of BP peaks and TAPV.

TAKEAWAY:

• Children with MS OSA had a TAPV for diastolic BP in the morning, an average of 51 minutes earlier than controls (P < .001).
• Evening TAPV was significantly earlier in the children with MS OSA than in controls for both systolic BP (SBP) and diastolic BP (DBP) (95 min, P < .001 and 28 min, P = .028, respectively).
• Midday SBP and DBP velocity nadirs were significantly earlier in the children with MS OSA than in controls (57 min, P < .001 and 38 min, P < .01, respectively).
• Overall, children with MS OSA reached most BP values significantly earlier than controls, and both SBP and DBP were significantly elevated in the MS OSA group compared with the control group.

IN PRACTICE:

“The findings provide an essential puzzle piece in our understanding of the cardiovascular effects of OSA in children,” wrote the authors of an accompanying editorial.

SOURCE:

The lead author of the study was Md Tareq Ferdous Khan, MD, of the University of Cincinnati, Cincinnati, Ohio; the authors of the accompanying editorial were Kate Ching-Ching Chan, MD, and Albert Martin Li, MD, of the Chinese University of Hong Kong, China. The study was published online in the journal Sleep on December 13, 2023, along with the accompanying editorial.

LIMITATIONS:

More research is needed to investigate the potential mechanisms of action, optimize methodology, and investigate circadian biology via actigraphy and biomarkers, the authors of an accompanying editorial wrote.

DISCLOSURES:

The study received no outside funding. The researchers and editorialists had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

The mechanisms underlying poststroke depression (PSD), a common and debilitating complication of stroke, are unclear. Is it neurobiological, psychosocial, or both?

Two studies offer new insight into this question. In the first, investigators systematically reviewed studies comparing stroke and non-stroke participants with depression and found the groups were similar in most dimensions of depressive symptoms. But surprisingly, anhedonia was less severe in patients with PSD compared with non-stroke controls, and those with PSD also showed greater emotional dysregulation.

“Our findings support previous recommendations that clinicians should adapt the provision of psychological support to the specific needs and difficulties of stroke survivors,” said lead author Joshua Blake, DClinPsy, lecturer in clinical psychology, University of East Anglia, Norwich, United Kingdom.

The study was published online in Neuropsychology Review

A second study used a machine learning algorithm to analyze blood samples from adults who had suffered a stroke, determining whether plasma protein data could predict mood and identifying potential proteins associated with mood in these patients.

“We can now look at a stroke survivor’s blood and predict their mood,” senior author Marion Buckwalter, MD, PhD, professor of neurology and neurosurgery at Stanford Medicine, California, said in a news release. “This means there is a genuine association between what’s happening in the blood and what’s happening with a person’s mood. It also means that, down the road, we may be able to develop new treatments for PSD.”

The study was published in November 2023 in Brain, Behavior, and Immunity.
 

‘Surprising’ Findings

“There has long been uncertainty over whether PSD might differ in its causes, phenomenology, and treatability, due to the presence of brain injury, related biological changes, and the psychosocial context unique to this population,” Dr. Blake said. “We felt that understanding symptomatologic similarities and differences would constructively contribute to this debate.”

The researchers reviewed 12 papers that sampled both stroke and non-stroke participants. “We compared profiles of depression symptoms, correlation strengths of individual depression symptoms with general depression, and latent item severity,” Dr. Blake reported.

They extracted 38 symptoms from five standardized depression tools and then organized the symptoms into nine dimensions.

They found mostly nonsignificant differences between patients with PSD and non-stroke controls in most dimensions, including negative affect, negative cognitions, somatic features, anxiety/worry, and suicidal ideation. Those with PSD more frequently had cognitive impairment, and “work inhibition” was more common in PSD.

But the most striking finding was greater severity/prevalence of emotional dysregulation in PSD vs non-stroke depression and also less anhedonia.

Dr. Blake acknowledged being “surprised.”

One possible explanation is that stroke recovery “appears to be a highly emotional journey, with extreme findings of both positive and negative emotions reported by survivors as they psychologically adjust,” which might be protective against anhedonia, he suggested.

Moreover, neurologically driven emotional dysregulation “may similarly reduce experiences of anhedonia.”

However, there was a “considerable risk of bias in many of the included studies, meaning it’s important that these findings are experimentally confirmed before stronger conclusions about phenomenological differences can be drawn,” he cautioned.
 

Common, Undertreated

Dr. Buckwalter said her team was motivated to conduct the research because PSD is among the top problems reported by chronic stroke patients, and for most, it is not adequately treated.

However, “despite the high prevalence of PSD, it is very poorly studied in the chronic time period.” In particular, PSD isn’t “well understood at a molecular level.”

She added that inflammation is a “promising candidate” as a mechanism, since neuroinflammation occurs in the stroke scar for decades, and chronic peripheral inflammation can produce neuroinflammation. Aberrant immune activation has also been implicated in major depression without stroke. But large studies with broad panels of plasma biomarkers are lacking in PSD.

To address this gap, the researchers used a proteomic approach. They recruited 85 chronic stroke patients (mean age, 65 years [interquartile range, 55-71], 41.2% female, 65.9% White, 17.6% Asian, and 0% Black) from the Stanford Stroke Recovery Program. Participants were between 5 months and 9 years after an ischemic stroke.

They analyzed a comprehensive panel of 1196 proteins in plasma samples, applying a machine learning algorithm to see whether the plasma protein levels “could be used to predict mood scores, using either the proteomics data alone or adding age and time since stroke.” The proteomics data were then incorporated into multivariable regression models, along with relevant clinical features, to ascertain the model’s predictive ability.

Mood was assessed using the Stroke Impact Scale mood questionnaire, with participants’ mood dichotomized into better mood (> 63) or worse mood (≤ 63).
 

‘Beautiful Mechanistic Model’

Machine learning verified a relationship between plasma proteomic data and mood, with the most accurate prediction occurring when the researchers added age and time since the stroke to the analysis.

Independent univariate analyses identified 202 proteins that were most highly correlated with mood in PSD. These were then organized into functional groups, including immune proteins, integrins, growth factors, synaptic function proteins, serotonin activity-related proteins, and cell death and stress-related functional groupings.

Although no single protein could predict depression, significant changes in levels of several proteins were found in PSD patients. A high proportion (45%) were proteins previously implicated in major depression, “likely providing a link to the underlying mechanisms of chronic PSD,” the authors stated.

Moreover, 80% of correlated immune proteins were higher in the plasma of people with worse mood, and several immune proteins known to have anti-inflammatory effects were reduced in those with worse mood.

And several pro-inflammatory cytokines were implicated. For example, interleukin 6, which has been extensively studied as a potential plasma marker of major depression in non-stroke cohorts, was significantly elevated in patients with worse mood after stroke (P = .0325), «implicating a broadly overactive immune system in PSD.»

“We demonstrated for the first time that we can use plasma protein measurements to predict mood in people with chronic stroke,” Dr. Buckwalter summarized. “This means there is a biological correlate of mood but [it] doesn’t tell us causality.”

To tease out causality, the researchers used their own data, as well as information from a literature review of previous studies, to assemble a model of how the immune response following a stroke could change both serotonin and brain plasticity.

“We used the most highly correlated proteins to construct a beautiful mechanistic model of how poststroke depression may work and how it may relate to mechanisms in major depression,” Dr. Buckwalter said.

The model “posits an increased inflammatory response that leads to decreased tryptophan, serotonin, and less synaptic function, all of which contribute to symptoms of depression.”

Currently, selective serotonin reuptake inhibitors represent the “best treatment” for people with PSD, but “unfortunately they don’t work for many patients,” Dr. Buckwalter noted. The findings “provide clues as to other molecular targets that are candidates novel therapies for poststroke depression.”

Dr. Blake commented that the proteomic study “complements the work by us and others interested in understanding PSD.”

Mood disorders “must be understood in terms of the dynamic relationships between structural neurological alterations, cellular and microbiological changes, psychological processes, and the person’s interactions with their social landscape,” Dr. Blake said.
 

New Treatments on the Horizon?

Gustavo C. Medeiros, MD, assistant professor, Department of Psychiatry, of the University of Maryland School of Medicine, Baltimore, said that knowing which individuals are more likely to develop PSD “allows treatment teams to implement earlier and more intensive interventions in those who are at higher risk.”

The findings [of the proteomic study] may also “help clarify the neurobiological correlates of PSD…[which] may help the development of new treatments that target these neurobiological changes,” said Dr. Medeiros, who wasn’t involved with either study.

However, he warned, “we should interpret their results with caution due to methodological reasons, including the relatively small sample size.”

Also commenting, Bruce Ovbiagele, MD, MSc, MAS, MBA, MLS, professor of neurology, UCSF Weill Institute for Neurosciences, California, said the proteomic study has some “clear limitations,” including the lack of Black or African American patients in the cohort, which limits generalizability, “since we know that Black and African American people are disproportionately affected by stroke and have very high rates of PSD and very severe presentation.”

The study by Dr. Blake et al. “was interesting because the phenotype of depressive symptoms after stroke differs from what’s seen in the general population, and the authors figured out a way to better understand the nuances of such differences,” said Dr. Ovbiagele, who wasn’t involved with either study.

He said he was also surprised by the finding regarding anhedonia and suggested that the findings be replicated in a study directly comparing patients with PSD and patients with depression from the general population.

The study by Bidoki et al. was funded by AHA/Paul Allen Foundation, the Leducq Stroke-IMPaCT Transatlantic Network of Excellence (MSB), the Wu Tsai Neurosciences Institute (MSB), the Alfred E. Mann Foundation (NA), and an Alzheimer’s Association Research Fellowship to one of the authors. No source of funding was listed for the study by Dr. Blake et al. The authors of both studies, Dr. Medeiros and Dr. Ovbiagele, declare no relevant financial relationships.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.

A first-of-its-kind partial heart transplant in a neonate delivered valves that continue to grow and function beyond 1 year of age, researchers said.

The surgery was performed on the 18th day of life of a 5-pound newborn boy diagnosed prenatally with persistent truncus arteriosus and severe truncal valve dysfunction. The procedure involved transplantation of the part of the heart containing the aorta and pulmonary valves from an infant donor upon cardiac death.

The standard of care for neonatal heart valve implants are cadaver grafts. But these grafts are not viable and can’t grow or self-repair. Therefore, recipient neonates need to undergo repeated implant-exchange surgeries until an adult-sized heart valve can fit. Clinical outcomes generally are poor.

“We have learned that these partial heart transplant valves, when procured fresh and the [recipient] baby is placed on low-dose antirejection medicine, can grow with the child and function completely normally,” Joseph W. Turek, MD, PhD, MBA of Duke University Medical Center in Durham, North Carolina, told this news organization.

“This represents a new field in heart surgery that could dramatically change the way we care for children with poorly functioning heart valves by allowing valve implants that grow with them.”

A case report describing the novel intervention was published online on January 2, 2024, in JAMA.

‘Expected to Last a Lifetime’

The donor was a 2-day-old female weighing 8 pounds. Delivery had been complicated by hypoxic ischemic brain injury, but echocardiography showed structurally normal, functioning outflow heart valves. The heart was donated after cardiac death and procured using standard surgical techniques.

The recipient infant’s operation involved sternotomy, cardiopulmonary bypass, and cardioplegic arrest of the heart. The pulmonary artery ostia and coronary artery buttons were dissected, and the infant’s irreparable truncal valve was excised.

The donor aortic root was transplanted first, using donor tissue to close the ventricular septal defect. Then, the coronary artery buttons were reimplanted; the right ventricular outflow tract was enlarged; and the pulmonary root was transplanted. Postoperative immunosuppression followed.

On the follow-up at age 14 months, the transplanted valves showed no obstruction or insufficiency on echocardiography. Now, almost 21 months later, the recipient is doing well, Dr. Turek said. “His family has shared his many milestones with me, including eating his first birthday cake, videos of his first steps, and his newfound oral appetite (he was largely g-tube fed for a while).”

“The rationale for partial heart transplant is that pediatric heart transplants grow,” Dr. Turek and coauthors wrote. “Moreover, failure of heart transplant outflow valves is exceedingly rare. While heart transplant long-term outcomes are limited by inevitable ventricular dysfunction, partial heart transplants spare the native ventricles and are therefore expected to last a lifetime.”

‘Domino Hearts’

“While this particular baby had truncus arteriosus, this operation should prove to be beneficial for a host of congenital heart conditions with valves that are either too small or poorly functioning,” Dr. Turek said. “We have performed subsequent partial heart operations for babies with aortic stenosis, tetralogy of Fallot with pulmonary atresia, and biventricular outflow tract obstruction.”

The challenge is organ availability, he noted. “While this procedure does make use of hearts that would be otherwise unusable for full heart transplant, such as hearts with poor ventricular function or hearts removed from recipients of full heart transplants (aka domino hearts), the availability is still low compared to the need.”

With domino hearts, “you could potentially double the number of hearts that are used for the benefit of children with heart disease,” Dr. Turek said in a Duke communication released with the paper. In a domino heart procedure, a patient who has healthy valves but needs stronger heart muscle receives a full heart transplant, and the healthy valves are then donated to another patient in need, creating a domino effect.

Since this breakthrough procedure in 2022, partial heart transplants have been performed 13 times at four centers, including nine at Duke, three of which used the domino technique.

For now, Dr. Turek told this news organization, “we are hoping to receive funds for a clinical trial that will evaluate these partial heart transplant valves on a larger basis and determine an optimal antirejection dose necessary to maintain viability.”

Preclinical research leading to this case report was supported by the Brett Boyer Foundation. Dr. Turek reported no conflicts of interest.

A version of this article appeared on Medscape.com.