MDedge Neurology

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. The authors declared no conflicts of interest.

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

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. The authors declared no conflicts of interest.

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

TOPLINE: 

In patients with giant cell arteritis (GCA), intravenous methylprednisolone compared with oral glucocorticoids alone does not improve visual acuity and increases the risk for diabetes within the first year. Survival rates do not differ with these two treatments.

METHODOLOGY:

• Researchers conducted a population-based retrospective study at three centers in Sweden to assess the clinical characteristics, treatment-related toxicity, and mortality in patients with GCA who were receiving high-dose intravenous methylprednisolone.
• A total of 419 patients with biopsy-confirmed GCA (mean age at diagnosis, 75 years; 69% women) diagnosed from 2004 to 2019 were included.
• Patients were treated with either intravenous methylprednisolone (n = 111) at a dose of 500-1000 mg per day for 3 consecutive days or oral glucocorticoids alone (n = 308).
• Ischemic visual complications considered to indicate visual involvement were confirmed by an ophthalmologist, and data on visual acuity were collected from ophthalmologic clinic records at initial consultations and follow-up at 3-18 months.

TAKEAWAY:

• Despite a tendency toward improvement, no significant difference in visual acuity was observed with intravenous methylprednisolone compared with oral glucocorticoids.
• Patients treated with intravenous methylprednisolone had a higher risk for newly diagnosed diabetes within a year of GCA diagnosis (odds ratio [OR], 2.59; P = .01).
• The risk for diabetes remained elevated even after adjustment for the cumulative oral glucocorticoid dose at 3 months (adjusted OR, 3.30; P = .01).
• Survival rates did not significantly differ between the treatment groups over a mean follow-up of 6.6 years.

IN PRACTICE:

“In this study on the use of intravenous methylprednisolone treatment in GCA, we found no evidence of a beneficial effect in improving visual acuity or enabling more rapid tapering of the oral glucocorticoid dose,” the authors wrote. “The use of IVMP [intravenous methylprednisolone] was associated with an increased risk of diabetes during the first year compared with oral GC [glucocorticoid], raising questions about the value of IVMP in GCA treatment.”

SOURCE:

The study, led by Hampus Henningson, Department of Clinical Sciences, Rheumatology, Lund University, Lund, Sweden, was published online in Rheumatology.

LIMITATIONS: 

The retrospective nature of the study may have resulted in missing data and difficulty in accurately quantifying the cumulative glucocorticoid doses. The study did not validate the diagnoses of comorbidities but relied solely on diagnostic codes.

DISCLOSURES:

This study was supported by the Swedish Research Council, Swedish Rheumatism Association, Swedish Medical Society, Alfred Österlund’s Foundation, and King Gustaf V’s 80-year foundation. The authors declared no conflicts of interest.

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

Combining cognitive remediation with transcranial direct current stimulation (tDCS) was associated with slower cognitive decline for up to 6 years in older adults with major depressive disorder that is in remission (rMDD), mild cognitive impairment (MCI), or both, new research suggests.

The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function. 

Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease. 

“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto. 

The findings were published online in JAMA Psychiatry. 
 

High-Risk Group

Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.

A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.

The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.

Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.

tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.

The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted. 

A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months). 

Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.

To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.

Study participants and assessors were blinded to treatment assignment.
 

Slower Cognitive Decline

Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory. 

“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.

The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant. 

The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.

“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant. 

These results suggest the pathways to dementia among people with MCI and rMDD are different, he added. 

Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two. 

The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education. 
 

Promising, Important Findings

Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.

The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.

“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry. 

The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Combining cognitive remediation with transcranial direct current stimulation (tDCS) was associated with slower cognitive decline for up to 6 years in older adults with major depressive disorder that is in remission (rMDD), mild cognitive impairment (MCI), or both, new research suggests.

The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function. 

Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease. 

“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto. 

The findings were published online in JAMA Psychiatry. 
 

High-Risk Group

Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.

A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.

The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.

Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.

tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.

The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted. 

A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months). 

Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.

To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.

Study participants and assessors were blinded to treatment assignment.
 

Slower Cognitive Decline

Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory. 

“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.

The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant. 

The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.

“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant. 

These results suggest the pathways to dementia among people with MCI and rMDD are different, he added. 

Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two. 

The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education. 
 

Promising, Important Findings

Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.

The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.

“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry. 

The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.

A version of this article appeared on Medscape.com.

Combining cognitive remediation with transcranial direct current stimulation (tDCS) was associated with slower cognitive decline for up to 6 years in older adults with major depressive disorder that is in remission (rMDD), mild cognitive impairment (MCI), or both, new research suggests.

The cognitive remediation intervention included a series of progressively difficult computer-based and facilitator-monitored mental exercises designed to sharpen cognitive function. 

Researchers found that using cognitive remediation with tDCS slowed decline in executive function and verbal memory more than other cognitive functions. The effect was stronger among people with rMDD versus those with MCI and in those at low genetic risk for Alzheimer’s disease. 

“We have developed a novel intervention, combining two interventions that if used separately have a weak effect but together have substantial and clinically meaningful effect of slowing the progression of cognitive decline,” said study author Benoit H. Mulsant, MD, chair of the Department of Psychiatry, University of Toronto, Ontario, Canada, and senior scientist at the Center for Addiction and Mental Health, also in Toronto. 

The findings were published online in JAMA Psychiatry. 
 

High-Risk Group

Research shows that older adults with MDD or MCI are at high risk for cognitive decline and dementia. Evidence also suggests that depression in early or mid-life significantly increases the risk for dementia in late life, even if the depression has been in remission for decades.

A potential mechanism underlying this increased risk for dementia could be impaired cortical plasticity, or the ability of the brain to compensate for damage.

The PACt-MD trial included 375 older adults with rMDD, MCI, or both (mean age, 72 years; 62% women) at five academic hospitals in Toronto.

Participants received either cognitive remediation plus tDCS or sham intervention 5 days per week for 8 weeks (acute phase), followed by 5-day “boosters” every 6 months.

tDCS was administered by trained personnel and involved active stimulation for 30 minutes at the beginning of each cognitive remediation group session. The intervention targets the prefrontal cortex, a critical region for cognitive compensation in normal cognitive aging.

The sham group received a weakened version of cognitive remediation, with exercises that did not get progressively more difficult. For the sham stimulation, the current flowed at full intensity for only 54 seconds before and after 30-second ramp-up and ramp-down phases, to create a blinding effect, the authors noted. 

A geriatric psychiatrist followed all participants throughout the study, conducting assessments at baseline, month 2, and yearly for 3-7 years (mean follow-up, 48.3 months). 

Participants’ depressive symptoms were evaluated at baseline and at all follow-ups and underwent neuropsychological testing to assess six cognitive domains: processing speed, working memory, executive functioning, verbal memory, visual memory, and language.

To get a norm for the cognitive tests, researchers recruited a comparator group of 75 subjects similar in age, gender, and years of education, with no neuropsychiatric disorder or cognitive impairment. They completed the same assessments but not the intervention.

Study participants and assessors were blinded to treatment assignment.
 

Slower Cognitive Decline

Participants in the intervention group had a significantly slower decline in cognitive function, compared with those in the sham group (adjusted z score difference [active – sham] at month 60, 0.21; P = .006). This is equivalent to slowing cognitive decline by about 4 years, researchers reported. The intervention also showed a positive effect on executive function and verbal memory. 

“If I can push dementia from 85 to 89 years and you die at 86, in practice, I have prevented you from ever developing dementia,” Mulsant said.

The efficacy of cognitive remediation plus tDCS in rMDD could be tied to enhanced neuroplasticity, said Mulsant. 

The treatment worked well in people with a history of depression, regardless of MCI status, but was not as effective for people with just MCI, researchers noted. The intervention also did not work as well among people at genetic risk for Alzheimer’s disease.

“We don’t believe we have discovered an intervention to prevent dementia in people who are at high risk for Alzheimer disease, but we have discovered an intervention that could prevent dementia in people who have an history of depression,” said Mulsant. 

These results suggest the pathways to dementia among people with MCI and rMDD are different, he added. 

Because previous research showed either treatment alone demonstrated little efficacy, researchers said the new results indicate that there may be a synergistic effect of combining the two. 

The ideal amount of treatment and optimal age for initiation still need to be determined, said Mulsant. The study did not include a comparator group without rMDD or MCI, so the observed cognitive benefits might be specific to people with these high-risk conditions. Another study limitation is lack of diversity in terms of ethnicity, race, and education. 
 

Promising, Important Findings

Commenting on the research, Badr Ratnakaran, MD, assistant professor and division director of geriatric psychiatry at Carilion Clinic–Virginia Tech Carilion School of Medicine, Roanoke, said the results are promising and important because there are so few treatment options for the increasing number of older patients with depression and dementia.

The side-effect profile of the combined treatment is better than that of many pharmacologic treatments, Ratnakaran noted. As more research like this comes out, Ratnakaran predicts that cognitive remediation and tCDS will become more readily available.

“This is telling us that the field of psychiatry, and also dementia, is progressing beyond your usual pharmacotherapy treatments,” said Ratnakaran, who also is chair of the American Psychiatric Association’s Council on Geriatric Psychiatry. 

The study received support from the Canada Brain Research Fund of Brain Canada, Health Canada, the Chagnon Family, and the Centre for Addiction and Mental Health Discovery Fund. Mulsant reported holding and receiving support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto; being a member of the Center for Addiction and Mental Health Board of Trustees; research support from Brain Canada, Canadian Institutes of Health Research, Center for Addiction and Mental Health Foundation, Patient-Centered Outcomes Research Institute, and National Institutes of Health; and nonfinancial support from Capital Solution Design and HappyNeuron. Ratnakaran reported no relevant conflicts.

A version of this article appeared on Medscape.com.

A finger-prick blood test can accurately identify p-tau217 — a key biomarker of Alzheimer’s disease — without the need for temperature or storage control measures.

In a pilot study, researchers found a good correlation of p-tau217 levels from blood obtained via standard venous sampling and from a single finger prick.

“We see the potential that capillary p-tau217 from dried blood spots could overcome the limitations of standard venous collection of being invasive, dependent on centrifuges and ultra-low temperature freezers, and also requiring less volume than standard plasma analysis,” said lead investigator Hanna Huber, PhD, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden. 

The findings were presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
 

Strong Link Between Venous and Capillary Samples 

p-tau217 has emerged as the most effective blood test to identify Alzheimer’s disease. However, traditional venous blood sampling requires certain infrastructure and immediate processing. Increased and simplified access to this blood biomarker could be crucial for early diagnosis, proper patient management, and prompt initiation of disease-modifying treatments. 

The DROP-AD project is investigating the diagnostic performance of finger-prick collection to accurately measure p-tau217. In the current study, the research team obtained paired venous blood and capillary blood samples from 206 adults (mean age, 71.8 years; 59% women), with or without cognitive impairment, from five European centers. A subset of participants provided a second finger-prick sample collected without any supervision. 

The capillary blood samples were obtained via a single finger prick, and then single blood drops were applied to a dried plasma spot (DPS) card, which was then shipped to a lab (without temperature control or cooling) for p-tau217 measurement. Cerebrospinal fluid biomarkers were available for a subset of individuals.

Throughout the entire study population, there was a “very convincing correlation” between p-tau217 levels from capillary DPS and venous plasma, Huber told conference attendees. 

Additionally, capillary DPS p-tau217 levels were able to discriminate amyloid-positive from amyloid-negative individuals, with levels of this biomarker increasing in a stepwise fashion, “from cognitively unimpaired individuals to individuals with mild cognitive impairment and, finally, to dementia patients,” Huber said.

Of note, capillary p-tau217 levels from DPS samples that were collected by research staff did not differ from unsupervised self-collected samples. 

What about the stability of the samples? Capillary DPS p-tau-217 is “stable over 2 weeks at room temperature,” Huber said. 
 

Ready for Prime Time?

Preliminary data from the DROP-AD project highlight the potential of using finger-prick blood collection to identify neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), two other Alzheimer’s disease biomarkers.

“We think that capillary p-tau217, but also other biomarkers, could be a widely accessible and cheap alternative for clinical practice and clinical trials in individuals with cognitive decline if the results are confirmed in longitudinal and home-sampling cohorts,” Huber concluded. 

“Measuring biomarkers by a simple finger prick could facilitate regular and autonomous sampling at home, which would be particularly useful in remote and rural settings,” she noted. 

The findings in this study confirm and extend earlier findings that the study team reported last year at the Alzheimer’s Association International Conference (AAIC). 

“The data shared at CTAD 2024, along with the related material previously presented at AAIC 2023, reporting on a ‘finger prick’ blood test approach is interesting and emerging work but not yet ready for clinical use,” said Rebecca M. Edelmayer, PhD, Alzheimer’s Association vice president of scientific engagement.

“That said, the idea of a highly accessible and scalable tool that can aid in easier and more equitable diagnosis would be welcomed by researchers, clinicians, and individuals and families affected by Alzheimer’s disease and all other dementias,” Edelmayer said.

“This finger-prick blood testing technology for Alzheimer’s biomarkers still has to be validated more broadly, but it is very promising. Advancements in technology and practice demonstrate the simplicity, transportability, and diagnostic value of blood-based biomarkers for Alzheimer’s,” she added. 

The Alzheimer’s Association is currently conducting a systematic review of the evidence and preparing clinical practice guidelines on blood-based biomarker tests for specialized healthcare settings, with publications, clinical resources, and tools anticipated in 2025, Edelmayer noted. 

The study had no commercial funding. Huber and Edelmayer report no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A finger-prick blood test can accurately identify p-tau217 — a key biomarker of Alzheimer’s disease — without the need for temperature or storage control measures.

In a pilot study, researchers found a good correlation of p-tau217 levels from blood obtained via standard venous sampling and from a single finger prick.

“We see the potential that capillary p-tau217 from dried blood spots could overcome the limitations of standard venous collection of being invasive, dependent on centrifuges and ultra-low temperature freezers, and also requiring less volume than standard plasma analysis,” said lead investigator Hanna Huber, PhD, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden. 

The findings were presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
 

Strong Link Between Venous and Capillary Samples 

p-tau217 has emerged as the most effective blood test to identify Alzheimer’s disease. However, traditional venous blood sampling requires certain infrastructure and immediate processing. Increased and simplified access to this blood biomarker could be crucial for early diagnosis, proper patient management, and prompt initiation of disease-modifying treatments. 

The DROP-AD project is investigating the diagnostic performance of finger-prick collection to accurately measure p-tau217. In the current study, the research team obtained paired venous blood and capillary blood samples from 206 adults (mean age, 71.8 years; 59% women), with or without cognitive impairment, from five European centers. A subset of participants provided a second finger-prick sample collected without any supervision. 

The capillary blood samples were obtained via a single finger prick, and then single blood drops were applied to a dried plasma spot (DPS) card, which was then shipped to a lab (without temperature control or cooling) for p-tau217 measurement. Cerebrospinal fluid biomarkers were available for a subset of individuals.

Throughout the entire study population, there was a “very convincing correlation” between p-tau217 levels from capillary DPS and venous plasma, Huber told conference attendees. 

Additionally, capillary DPS p-tau217 levels were able to discriminate amyloid-positive from amyloid-negative individuals, with levels of this biomarker increasing in a stepwise fashion, “from cognitively unimpaired individuals to individuals with mild cognitive impairment and, finally, to dementia patients,” Huber said.

Of note, capillary p-tau217 levels from DPS samples that were collected by research staff did not differ from unsupervised self-collected samples. 

What about the stability of the samples? Capillary DPS p-tau-217 is “stable over 2 weeks at room temperature,” Huber said. 
 

Ready for Prime Time?

Preliminary data from the DROP-AD project highlight the potential of using finger-prick blood collection to identify neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), two other Alzheimer’s disease biomarkers.

“We think that capillary p-tau217, but also other biomarkers, could be a widely accessible and cheap alternative for clinical practice and clinical trials in individuals with cognitive decline if the results are confirmed in longitudinal and home-sampling cohorts,” Huber concluded. 

“Measuring biomarkers by a simple finger prick could facilitate regular and autonomous sampling at home, which would be particularly useful in remote and rural settings,” she noted. 

The findings in this study confirm and extend earlier findings that the study team reported last year at the Alzheimer’s Association International Conference (AAIC). 

“The data shared at CTAD 2024, along with the related material previously presented at AAIC 2023, reporting on a ‘finger prick’ blood test approach is interesting and emerging work but not yet ready for clinical use,” said Rebecca M. Edelmayer, PhD, Alzheimer’s Association vice president of scientific engagement.

“That said, the idea of a highly accessible and scalable tool that can aid in easier and more equitable diagnosis would be welcomed by researchers, clinicians, and individuals and families affected by Alzheimer’s disease and all other dementias,” Edelmayer said.

“This finger-prick blood testing technology for Alzheimer’s biomarkers still has to be validated more broadly, but it is very promising. Advancements in technology and practice demonstrate the simplicity, transportability, and diagnostic value of blood-based biomarkers for Alzheimer’s,” she added. 

The Alzheimer’s Association is currently conducting a systematic review of the evidence and preparing clinical practice guidelines on blood-based biomarker tests for specialized healthcare settings, with publications, clinical resources, and tools anticipated in 2025, Edelmayer noted. 

The study had no commercial funding. Huber and Edelmayer report no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

A finger-prick blood test can accurately identify p-tau217 — a key biomarker of Alzheimer’s disease — without the need for temperature or storage control measures.

In a pilot study, researchers found a good correlation of p-tau217 levels from blood obtained via standard venous sampling and from a single finger prick.

“We see the potential that capillary p-tau217 from dried blood spots could overcome the limitations of standard venous collection of being invasive, dependent on centrifuges and ultra-low temperature freezers, and also requiring less volume than standard plasma analysis,” said lead investigator Hanna Huber, PhD, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Sweden. 

The findings were presented at the 17th Clinical Trials on Alzheimer’s Disease (CTAD) conference.
 

Strong Link Between Venous and Capillary Samples 

p-tau217 has emerged as the most effective blood test to identify Alzheimer’s disease. However, traditional venous blood sampling requires certain infrastructure and immediate processing. Increased and simplified access to this blood biomarker could be crucial for early diagnosis, proper patient management, and prompt initiation of disease-modifying treatments. 

The DROP-AD project is investigating the diagnostic performance of finger-prick collection to accurately measure p-tau217. In the current study, the research team obtained paired venous blood and capillary blood samples from 206 adults (mean age, 71.8 years; 59% women), with or without cognitive impairment, from five European centers. A subset of participants provided a second finger-prick sample collected without any supervision. 

The capillary blood samples were obtained via a single finger prick, and then single blood drops were applied to a dried plasma spot (DPS) card, which was then shipped to a lab (without temperature control or cooling) for p-tau217 measurement. Cerebrospinal fluid biomarkers were available for a subset of individuals.

Throughout the entire study population, there was a “very convincing correlation” between p-tau217 levels from capillary DPS and venous plasma, Huber told conference attendees. 

Additionally, capillary DPS p-tau217 levels were able to discriminate amyloid-positive from amyloid-negative individuals, with levels of this biomarker increasing in a stepwise fashion, “from cognitively unimpaired individuals to individuals with mild cognitive impairment and, finally, to dementia patients,” Huber said.

Of note, capillary p-tau217 levels from DPS samples that were collected by research staff did not differ from unsupervised self-collected samples. 

What about the stability of the samples? Capillary DPS p-tau-217 is “stable over 2 weeks at room temperature,” Huber said. 
 

Ready for Prime Time?

Preliminary data from the DROP-AD project highlight the potential of using finger-prick blood collection to identify neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), two other Alzheimer’s disease biomarkers.

“We think that capillary p-tau217, but also other biomarkers, could be a widely accessible and cheap alternative for clinical practice and clinical trials in individuals with cognitive decline if the results are confirmed in longitudinal and home-sampling cohorts,” Huber concluded. 

“Measuring biomarkers by a simple finger prick could facilitate regular and autonomous sampling at home, which would be particularly useful in remote and rural settings,” she noted. 

The findings in this study confirm and extend earlier findings that the study team reported last year at the Alzheimer’s Association International Conference (AAIC). 

“The data shared at CTAD 2024, along with the related material previously presented at AAIC 2023, reporting on a ‘finger prick’ blood test approach is interesting and emerging work but not yet ready for clinical use,” said Rebecca M. Edelmayer, PhD, Alzheimer’s Association vice president of scientific engagement.

“That said, the idea of a highly accessible and scalable tool that can aid in easier and more equitable diagnosis would be welcomed by researchers, clinicians, and individuals and families affected by Alzheimer’s disease and all other dementias,” Edelmayer said.

“This finger-prick blood testing technology for Alzheimer’s biomarkers still has to be validated more broadly, but it is very promising. Advancements in technology and practice demonstrate the simplicity, transportability, and diagnostic value of blood-based biomarkers for Alzheimer’s,” she added. 

The Alzheimer’s Association is currently conducting a systematic review of the evidence and preparing clinical practice guidelines on blood-based biomarker tests for specialized healthcare settings, with publications, clinical resources, and tools anticipated in 2025, Edelmayer noted. 

The study had no commercial funding. Huber and Edelmayer report no relevant conflicts of interest. 
 

A version of this article appeared on Medscape.com.

Despite some recent progress in compensation equity, women in medicine continue to be paid significantly lower salaries than men.

According to the Female Compensation Report 2024 by Medscape, male doctors of any kind earned an average salary of about $400,000, whereas female doctors earned approximately $309,000 — a 29% gap.

The report analyzed survey data from 7000 practicing physicians who were recruited over a 4-month period starting in October 2023. The respondents comprised roughly 60% women representing over 29 specialties.

In the 2022 report, the pay gap between the genders was 32%. But some women in the field argued substantial headway is still needed.

“You can try and pick apart the data, but I’d say we’re not really making progress,” said Susan T. Hingle, MD, an internist in Illinois and president of the American Medical Women’s Association. “A decline by a couple of percentage points is not significantly addressing this pay gap that over a lifetime is huge, can be millions of dollars.”

The gender gap was narrower among female primary care physicians (PCPs) vs medical specialists. Female PCPs earned around $253,000 per year, whereas male PCPs earned about $295,000 per year. Hingle suggested that female PCPs may enjoy more pay equity because health systems have a harder time filling these positions.

On the other hand, the gap for specialists rose from 27% in 2022 to 31% in 2023. Differences in how aggressively women and men negotiate compensation packages may play a role, said Hingle.

“Taking negotiation out of the equation would be progress to me,” said Hingle.

Pay disparity did not appear to be the result of time spent on the job — female doctors reported an average of 49 work hours per week, whereas their male counterparts reported 50 work hours per week.

Meanwhile, the pay gap progressively worsened over time. Among doctors aged 28-34 years, men earned an average of $53,000 more than women. By ages 46-49, men earned an average of $157,000 more than women.

“I had to take my employer to court to get equal compensation, sad as it is to say,” said a hospitalist in North Carolina.

Nearly 60% of women surveyed felt they were not being paid fairly for their efforts, up from less than half reported in Medscape’s 2021 report. Hingle said that this figure may not only reflect sentiments about the compensation gap, but also less support on the job, including fewer physician assistants (PAs), nurses, and administrative staff.

“At my job, I do the work of multiple people,” said a survey respondent. “Junior resident, senior resident, social worker, nurse practitioner, PA — as well as try to be a teacher, researcher, [and] an excellent doctor and have the time to make patients feel as if they are not in a rush.”

Roughly 30% of women physicians said they would not choose to go into medicine again if given the chance compared with 26% of male physicians.

“Gender inequities in our profession have a direct impact,” said Shikha Jain, MD, an oncologist in Chicago and founder of the Women in Medicine nonprofit. “I think women in general don’t feel valued in the care they’re providing.” 

Jain cited bullying, harassment, and fewer opportunities for leadership and recognition as factors beyond pay that affect female physicians’ feelings of being valued.

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

Despite some recent progress in compensation equity, women in medicine continue to be paid significantly lower salaries than men.

According to the Female Compensation Report 2024 by Medscape, male doctors of any kind earned an average salary of about $400,000, whereas female doctors earned approximately $309,000 — a 29% gap.

The report analyzed survey data from 7000 practicing physicians who were recruited over a 4-month period starting in October 2023. The respondents comprised roughly 60% women representing over 29 specialties.

In the 2022 report, the pay gap between the genders was 32%. But some women in the field argued substantial headway is still needed.

“You can try and pick apart the data, but I’d say we’re not really making progress,” said Susan T. Hingle, MD, an internist in Illinois and president of the American Medical Women’s Association. “A decline by a couple of percentage points is not significantly addressing this pay gap that over a lifetime is huge, can be millions of dollars.”

The gender gap was narrower among female primary care physicians (PCPs) vs medical specialists. Female PCPs earned around $253,000 per year, whereas male PCPs earned about $295,000 per year. Hingle suggested that female PCPs may enjoy more pay equity because health systems have a harder time filling these positions.

On the other hand, the gap for specialists rose from 27% in 2022 to 31% in 2023. Differences in how aggressively women and men negotiate compensation packages may play a role, said Hingle.

“Taking negotiation out of the equation would be progress to me,” said Hingle.

Pay disparity did not appear to be the result of time spent on the job — female doctors reported an average of 49 work hours per week, whereas their male counterparts reported 50 work hours per week.

Meanwhile, the pay gap progressively worsened over time. Among doctors aged 28-34 years, men earned an average of $53,000 more than women. By ages 46-49, men earned an average of $157,000 more than women.

“I had to take my employer to court to get equal compensation, sad as it is to say,” said a hospitalist in North Carolina.

Nearly 60% of women surveyed felt they were not being paid fairly for their efforts, up from less than half reported in Medscape’s 2021 report. Hingle said that this figure may not only reflect sentiments about the compensation gap, but also less support on the job, including fewer physician assistants (PAs), nurses, and administrative staff.

“At my job, I do the work of multiple people,” said a survey respondent. “Junior resident, senior resident, social worker, nurse practitioner, PA — as well as try to be a teacher, researcher, [and] an excellent doctor and have the time to make patients feel as if they are not in a rush.”

Roughly 30% of women physicians said they would not choose to go into medicine again if given the chance compared with 26% of male physicians.

“Gender inequities in our profession have a direct impact,” said Shikha Jain, MD, an oncologist in Chicago and founder of the Women in Medicine nonprofit. “I think women in general don’t feel valued in the care they’re providing.” 

Jain cited bullying, harassment, and fewer opportunities for leadership and recognition as factors beyond pay that affect female physicians’ feelings of being valued.

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

Despite some recent progress in compensation equity, women in medicine continue to be paid significantly lower salaries than men.

According to the Female Compensation Report 2024 by Medscape, male doctors of any kind earned an average salary of about $400,000, whereas female doctors earned approximately $309,000 — a 29% gap.

The report analyzed survey data from 7000 practicing physicians who were recruited over a 4-month period starting in October 2023. The respondents comprised roughly 60% women representing over 29 specialties.

In the 2022 report, the pay gap between the genders was 32%. But some women in the field argued substantial headway is still needed.

“You can try and pick apart the data, but I’d say we’re not really making progress,” said Susan T. Hingle, MD, an internist in Illinois and president of the American Medical Women’s Association. “A decline by a couple of percentage points is not significantly addressing this pay gap that over a lifetime is huge, can be millions of dollars.”

The gender gap was narrower among female primary care physicians (PCPs) vs medical specialists. Female PCPs earned around $253,000 per year, whereas male PCPs earned about $295,000 per year. Hingle suggested that female PCPs may enjoy more pay equity because health systems have a harder time filling these positions.

On the other hand, the gap for specialists rose from 27% in 2022 to 31% in 2023. Differences in how aggressively women and men negotiate compensation packages may play a role, said Hingle.

“Taking negotiation out of the equation would be progress to me,” said Hingle.

Pay disparity did not appear to be the result of time spent on the job — female doctors reported an average of 49 work hours per week, whereas their male counterparts reported 50 work hours per week.

Meanwhile, the pay gap progressively worsened over time. Among doctors aged 28-34 years, men earned an average of $53,000 more than women. By ages 46-49, men earned an average of $157,000 more than women.

“I had to take my employer to court to get equal compensation, sad as it is to say,” said a hospitalist in North Carolina.

Nearly 60% of women surveyed felt they were not being paid fairly for their efforts, up from less than half reported in Medscape’s 2021 report. Hingle said that this figure may not only reflect sentiments about the compensation gap, but also less support on the job, including fewer physician assistants (PAs), nurses, and administrative staff.

“At my job, I do the work of multiple people,” said a survey respondent. “Junior resident, senior resident, social worker, nurse practitioner, PA — as well as try to be a teacher, researcher, [and] an excellent doctor and have the time to make patients feel as if they are not in a rush.”

Roughly 30% of women physicians said they would not choose to go into medicine again if given the chance compared with 26% of male physicians.

“Gender inequities in our profession have a direct impact,” said Shikha Jain, MD, an oncologist in Chicago and founder of the Women in Medicine nonprofit. “I think women in general don’t feel valued in the care they’re providing.” 

Jain cited bullying, harassment, and fewer opportunities for leadership and recognition as factors beyond pay that affect female physicians’ feelings of being valued.

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

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

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

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

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

Methadone has been shown to be highly effective for opioid use disorder. So why is it still so difficult to prescribe in the United States and is that about to change?

A recent study from Canada adds to the growing body of evidence supporting methadone’s effectiveness in treating opioid use disorder and bolsters efforts to expand access in the United States by removing restrictive barriers.

This paper included more than 30,000 patients with opioid use disorder and showed those on methadone were almost 60% significantly less likely to stop treatment at 24 months than their peers assigned to buprenorphine/naloxone (adjusted hazard ratio [aHR], 1.58), with no difference in mortality risk (aHR, 0.57).

“In Canada, unlike the US, methadone and buprenorphine/naloxone are both available in office-based settings. Methadone really outperforms buprenorphine/naloxone in being able to retain people in treatment, which is our main goal and comes with a host of benefits,” Bohdan Nosyk, PhD, with Simon Fraser University in Burnaby, British Columbia, Canada, who worked on the study, said in an interview.

In addition, a recent systematic review and meta-analysis of relevant research involving more than 1 million patients with opioid use disorder also showed better treatment retention with methadone than with buprenorphine.

During the COVID-19 pandemic, relaxed methadone regulations, that included take-home medications, did not lead to an increase in overdoses. Instead, these changes improved treatment retention and patient experiences, highlighting the potential benefits of further deregulation.
 

‘Atrocious’ Outdated Policies

However, despite methadone’s proven efficacy and safety for opioid use disorder, it remains vastly underutilized because of outdated US policies restricting its use to opioid treatment programs (OTPs).

“It’s absolutely atrocious that methadone policies have not kept up with the evidence. If you look at other countries that have expanded their access to methadone, their overdose rates have fallen dramatically,” said Leslie Suen, MD, with the University of California, San Francisco, and coauthor of a recent JAMA Viewpoint on this topic.

“Methadone is a very good medication that’s been shown over and over to be very effective and safe,” Alan Leshner, PhD, past director of the National Institute on Drug Abuse, said in an interview.

“There is no reason why it couldn’t be administered through pharmacies or through physicians’ offices as long as it’s done in a controlled and careful way,” said Leshner.

Leshner chaired the committee that produced the 2019 report Medications for Opioid Use Disorder Save Lives.

“We learned during COVID that increasing the amount of take-home methadone and increasing access does not lead to an increase in deaths or an increase in overdose, so it’s hard to find a reason not to do it,” he said.
 

Change Finally on the Horizon?

Several recent and proposed policy changes could revolutionize methadone delivery in the United States.

In March 2022, in response to the pandemic, the Drug Enforcement Administration (DEA) allowed hospitals to dispense up to a 3-day supply of methadone (known as the 72-hour rule) to bridge care transitions without needing OTPs.

In April 2024, the Substance Abuse and Mental Health Services Administration and DEA codified many methadone and buprenorphine delivery flexibilities granted temporarily during the pandemic, including increased use of telehealth assessments and earlier access to take-home methadone doses.

Another contemporary policy change is expansion of the Americans with Disabilities Act mandating that patients taking medications for opioid use disorder, such as methadone, be able to continue treatment when transitioning to settings such as hospitals, jails, and skilled nursing facilities.

At the state level, California Governor Gavin Newsom recently signed a bill, effective immediately, that expands access to methadone treatment in his state.

On the horizon at the federal level is the Modernizing Opioid Treatment Access Act (MOTAA) — the bipartisan and bicameral bill introduced by Sen. Ed Markey (D-MA) and Sen. Rand Paul (R-KY), along with Rep. Donald Norcross (D-NJ) and Rep. Don Bacon, (R-NE) — that would allow methadone to be prescribed by addiction specialists and dispensed in community pharmacies.
 

An Ethical Imperative

“With only about 2000 OTP clinics clustered in urban areas, less than 25% of people who are diagnosed with opioid use disorder are actually able to access methadone,” Caty Simon, with the National Survivors Union, Greensboro, North Carolina, and coauthor of the JAMA Viewpoint, said in an interview.

While MOTAA represents a major step forward, limiting methadone prescribing to addiction specialists may not fully address the treatment gap, particularly in rural and underserved areas, Simon said.

To optimize methadone’s potential, she’d like to see further expansion of prescribing privileges to general healthcare providers.

“As someone with lived and living experience of opioid use and treatment, and somebody who works nationally and locally in organizations of people impacted by drug use, I know people in my area right now — marginalized people of color — who would have much better chances of survival if they were able to access methadone. If MOTAA passed tomorrow, we could save so many lives. There is an ethical imperative to pass it,” Simon said.

Leshner said he is “always very concerned about access, particularly for underserved populations, poor people, people living in rural areas. If you can access the medications you need, you’re in big trouble.”

Is this methadone’s moment? “I’m a little optimistic, but I haven’t seen the progress I would like to see,” Leshner said.

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

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

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

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

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

The Food and Drug Administration (FDA) has approved a 10-mg dose of Roxybond (Protega Pharmaceuticals), an opioid analgesic indicated for the management of severe pain in cases where other treatments are not well-tolerated or prove ineffective.

Roxybond, an immediate-release (IR) formulation of oxycodone hydrochloride, is made with Protega’s SentryBond technology, which makes it harder for people to crush, inject, or snort, according to the company.

In a statement from Protega, Paul Howe, the company’s chief commercial officer, said the drug meets an “unmet need for an IR opioid with abuse-deterrent technology that may reduce misuse and abuse while providing pain relief to medically appropriate patients when used as indicated.”

To determine the tablet’s ability to withstand manipulation, more than 2000 in vitro tests were conducted, according to the release. The findings indicate Roxybond reduces — but does not entirely negate — the potential for intranasal and intravenous abuse.

Roxybond was previously approved in 5-, 15-, and 30-mg doses. The 10 mg option provides clinicians with the ability to better modify side effects, manage titration, and provide precision care for patients on opioid therapy, according to Protega.

“For patients, the range of doses can provide better pain control, reduce the risk of side effects, and provide a smoother transition during dosing transitions,” the company stated.

Roxybond is contraindicated in patients with significant respiratory depression, acute or severe bronchial asthma, gastrointestinal obstruction, or hypersensitivity to oxycodone. The drug is not intended for long-term use unless otherwise determined by a clinician. Roxybond also is subject to the FDA’s Risk Evaluation and Mitigation Strategies for opioids.

“The development of Roxybond with SentryBond is a step forward in fighting the national epidemic of prescription opioid overdose,” said Eric Kinzler, PhD, vice president of medical and regulatory affairs for Protega, in a release. “Protega is dedicated to our mission to block the path to abuse and work with healthcare professionals across the continuum of care to reduce misuse and abuse.”

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

In seconds, Ravi Parikh, MD, an oncologist at the Emory University School of Medicine in Atlanta, had a summary of his patient’s entire medical history. Normally, Parikh skimmed the cumbersome files before seeing a patient. However, the artificial intelligence (AI) tool his institution was testing could list the highlights he needed in a fraction of the time.

“On the whole, I like it ... it saves me time,” Parikh said of the tool. “But I’d be lying if I told you it was perfect all the time. It’s interpreting the [patient] history in some ways that may be inaccurate,” he said.

Within the first week of testing the tool, Parikh started to notice that the large language model (LLM) made a particular mistake in his patients with prostate cancer. If their prostate-specific antigen test results came back slightly elevated — which is part of normal variation — the LLM recorded it as disease progression. Because Parikh reviews all his notes — with or without using an AI tool — after a visit, he easily caught the mistake before it was added to the chart. “The problem, I think, is if these mistakes go under the hood,” he said.

In the data science world, these mistakes are called hallucinations. And a growing body of research suggests they’re happening more frequently than is safe for healthcare. The industry promised LLMs would alleviate administrative burden and reduce physician burnout. But so far, studies show these AI-tool mistakes often create more work for doctors, not less. To truly help physicians and be safe for patients, some experts say healthcare needs to build its own LLMs from the ground up. And all agree that the field desperately needs a way to vet these algorithms more thoroughly.
 

Prone to Error

Right now, “I think the industry is focused on taking existing LLMs and forcing them into usage for healthcare,” said Nigam H. Shah, MBBS, PhD, chief data scientist for Stanford Health. However, the value of deploying general LLMs in the healthcare space is questionable. “People are starting to wonder if we’re using these tools wrong,” he told this news organization.

In 2023, Shah and his colleagues evaluated seven LLMs on their ability to answer electronic health record–based questions. For realistic tasks, the error rate in the best cases was about 35%, he said. “To me, that rate seems a bit high ... to adopt for routine use.”

A study earlier this year by the UC San Diego School of Medicine showed that using LLMs to respond to patient messages increased the time doctors spent on messages. And this summer, a study by the clinical AI firm Mendel found that when GPT-4o or Llama-3 were used to summarize patient medical records, almost every summary contained at least one type of hallucination.

“We’ve seen cases where a patient does have drug allergies, but the system says ‘no known drug allergies’ ” in the medical history summary, said Wael Salloum, PhD, cofounder and chief science officer at Mendel. “That’s a serious hallucination.” And if physicians have to constantly verify what the system is telling them, that “defeats the purpose [of summarization],” he said.
 

A Higher Quality Diet

Part of the trouble with LLMs is that there’s just not enough high-quality information to feed them. The algorithms are insatiable, requiring vast swaths of data for training. GPT-3.5, for instance, was trained on 570 GB of data from the internet, more than 300 billion words. And to train GPT-4o, OpenAI reportedly transcribed more than 1 million hours of YouTube content.

However, the strategies that built these general LLMs don’t always translate well to healthcare. The internet is full of low-quality or misleading health information from wellness sites and supplement advertisements. And even data that are trustworthy, like the millions of clinical studies and the US Food and Drug Administration (FDA) statements, can be outdated, Salloum said. And “an LLM in training can’t distinguish good from bad,” he added.

The good news is that clinicians don’t rely on controversial information in the real world. Medical knowledge is standardized. “Healthcare is a domain rich with explicit knowledge,” Salloum said. So there’s potential to build a more reliable LLM that is guided by robust medical standards and guidelines.

It’s possible that healthcare could use small language models, which are LLM’s pocket-sized cousins, and perform tasks needing only bite-sized datasets requiring fewer resources and easier fine-tuning, according to Microsoft’s website. Shah said training these smaller models on real medical data might be an option, like an LLM meant to respond to patient messages that could be trained with real messages sent by physicians.

Several groups are already working on databases of standardized human medical knowledge or real physician responses. “Perhaps that will work better than using LLMs trained on the general internet. Those studies need to be done,” Shah said.

Jon Tamir, assistant professor of electrical and computer engineering and co-lead of the AI Health Lab at The University of Texas at Austin, said, “The community has recognized that we are entering a new era of AI where the dataset itself is the most important aspect. We need training sets that are highly curated and highly specialized.

“If the dataset is highly specialized, it will definitely help reduce hallucinations,” he said.
 

Cutting Overconfidence

A major problem with LLM mistakes is that they are often hard to detect. Hallucinations can be highly convincing even if they’re highly inaccurate, according to Tamir.

When Shah, for instance, was recently testing an LLM on de-identified patient data, he asked the LLM which blood test the patient last had. The model responded with “complete blood count [CBC].” But when he asked for the results, the model gave him white blood count and other values. “Turns out that record did not have a CBC done at all! The result was entirely made up,” he said.

Making healthcare LLMs safer and more reliable will mean training AI to acknowledge potential mistakes and uncertainty. Existing LLMs are trained to project confidence and produce a lot of answers, even when there isn’t one, Salloum said. They rarely respond with “I don’t know” even when their prediction has low confidence, he added.

Healthcare stands to benefit from a system that highlights uncertainty and potential errors. For instance, if a patient’s history shows they have smoked, stopped smoking, vaped, and started smoking again. The LLM might call them a smoker but flag the comment as uncertain because the chronology is complicated, Salloum said.

Tamir added that this strategy could improve LLM and doctor collaboration by honing in on where human expertise is needed most.
 

Too Little Evaluation

For any improvement strategy to work, LLMs — and all AI-assisted healthcare tools — first need a better evaluation framework. So far, LLMs have “been used in really exciting ways but not really well-vetted ways,” Tamir said.

While some AI-assisted tools, particularly in medical imaging, have undergone rigorous FDA evaluations and earned approval, most haven’t. And because the FDA only regulates algorithms that are considered medical devices, Parikh said that most LLMs used for administrative tasks and efficiency don’t fall under the regulatory agency’s purview.

But these algorithms still have access to patient information and can directly influence patient and doctor decisions. Third-party regulatory agencies are expected to emerge, but it’s still unclear who those will be. Before developers can build a safer and more efficient LLM for healthcare, they’ll need better guidelines and guardrails. “Unless we figure out evaluation, how would we know whether the healthcare-appropriate large language models are better or worse?” Shah asked.
 

A version of this article appeared on Medscape.com.

In seconds, Ravi Parikh, MD, an oncologist at the Emory University School of Medicine in Atlanta, had a summary of his patient’s entire medical history. Normally, Parikh skimmed the cumbersome files before seeing a patient. However, the artificial intelligence (AI) tool his institution was testing could list the highlights he needed in a fraction of the time.

“On the whole, I like it ... it saves me time,” Parikh said of the tool. “But I’d be lying if I told you it was perfect all the time. It’s interpreting the [patient] history in some ways that may be inaccurate,” he said.

Within the first week of testing the tool, Parikh started to notice that the large language model (LLM) made a particular mistake in his patients with prostate cancer. If their prostate-specific antigen test results came back slightly elevated — which is part of normal variation — the LLM recorded it as disease progression. Because Parikh reviews all his notes — with or without using an AI tool — after a visit, he easily caught the mistake before it was added to the chart. “The problem, I think, is if these mistakes go under the hood,” he said.

In the data science world, these mistakes are called hallucinations. And a growing body of research suggests they’re happening more frequently than is safe for healthcare. The industry promised LLMs would alleviate administrative burden and reduce physician burnout. But so far, studies show these AI-tool mistakes often create more work for doctors, not less. To truly help physicians and be safe for patients, some experts say healthcare needs to build its own LLMs from the ground up. And all agree that the field desperately needs a way to vet these algorithms more thoroughly.
 

Prone to Error

Right now, “I think the industry is focused on taking existing LLMs and forcing them into usage for healthcare,” said Nigam H. Shah, MBBS, PhD, chief data scientist for Stanford Health. However, the value of deploying general LLMs in the healthcare space is questionable. “People are starting to wonder if we’re using these tools wrong,” he told this news organization.

In 2023, Shah and his colleagues evaluated seven LLMs on their ability to answer electronic health record–based questions. For realistic tasks, the error rate in the best cases was about 35%, he said. “To me, that rate seems a bit high ... to adopt for routine use.”

A study earlier this year by the UC San Diego School of Medicine showed that using LLMs to respond to patient messages increased the time doctors spent on messages. And this summer, a study by the clinical AI firm Mendel found that when GPT-4o or Llama-3 were used to summarize patient medical records, almost every summary contained at least one type of hallucination.

“We’ve seen cases where a patient does have drug allergies, but the system says ‘no known drug allergies’ ” in the medical history summary, said Wael Salloum, PhD, cofounder and chief science officer at Mendel. “That’s a serious hallucination.” And if physicians have to constantly verify what the system is telling them, that “defeats the purpose [of summarization],” he said.
 

A Higher Quality Diet

Part of the trouble with LLMs is that there’s just not enough high-quality information to feed them. The algorithms are insatiable, requiring vast swaths of data for training. GPT-3.5, for instance, was trained on 570 GB of data from the internet, more than 300 billion words. And to train GPT-4o, OpenAI reportedly transcribed more than 1 million hours of YouTube content.

However, the strategies that built these general LLMs don’t always translate well to healthcare. The internet is full of low-quality or misleading health information from wellness sites and supplement advertisements. And even data that are trustworthy, like the millions of clinical studies and the US Food and Drug Administration (FDA) statements, can be outdated, Salloum said. And “an LLM in training can’t distinguish good from bad,” he added.

The good news is that clinicians don’t rely on controversial information in the real world. Medical knowledge is standardized. “Healthcare is a domain rich with explicit knowledge,” Salloum said. So there’s potential to build a more reliable LLM that is guided by robust medical standards and guidelines.

It’s possible that healthcare could use small language models, which are LLM’s pocket-sized cousins, and perform tasks needing only bite-sized datasets requiring fewer resources and easier fine-tuning, according to Microsoft’s website. Shah said training these smaller models on real medical data might be an option, like an LLM meant to respond to patient messages that could be trained with real messages sent by physicians.

Several groups are already working on databases of standardized human medical knowledge or real physician responses. “Perhaps that will work better than using LLMs trained on the general internet. Those studies need to be done,” Shah said.

Jon Tamir, assistant professor of electrical and computer engineering and co-lead of the AI Health Lab at The University of Texas at Austin, said, “The community has recognized that we are entering a new era of AI where the dataset itself is the most important aspect. We need training sets that are highly curated and highly specialized.

“If the dataset is highly specialized, it will definitely help reduce hallucinations,” he said.
 

Cutting Overconfidence

A major problem with LLM mistakes is that they are often hard to detect. Hallucinations can be highly convincing even if they’re highly inaccurate, according to Tamir.

When Shah, for instance, was recently testing an LLM on de-identified patient data, he asked the LLM which blood test the patient last had. The model responded with “complete blood count [CBC].” But when he asked for the results, the model gave him white blood count and other values. “Turns out that record did not have a CBC done at all! The result was entirely made up,” he said.

Making healthcare LLMs safer and more reliable will mean training AI to acknowledge potential mistakes and uncertainty. Existing LLMs are trained to project confidence and produce a lot of answers, even when there isn’t one, Salloum said. They rarely respond with “I don’t know” even when their prediction has low confidence, he added.

Healthcare stands to benefit from a system that highlights uncertainty and potential errors. For instance, if a patient’s history shows they have smoked, stopped smoking, vaped, and started smoking again. The LLM might call them a smoker but flag the comment as uncertain because the chronology is complicated, Salloum said.

Tamir added that this strategy could improve LLM and doctor collaboration by honing in on where human expertise is needed most.
 

Too Little Evaluation

For any improvement strategy to work, LLMs — and all AI-assisted healthcare tools — first need a better evaluation framework. So far, LLMs have “been used in really exciting ways but not really well-vetted ways,” Tamir said.

While some AI-assisted tools, particularly in medical imaging, have undergone rigorous FDA evaluations and earned approval, most haven’t. And because the FDA only regulates algorithms that are considered medical devices, Parikh said that most LLMs used for administrative tasks and efficiency don’t fall under the regulatory agency’s purview.

But these algorithms still have access to patient information and can directly influence patient and doctor decisions. Third-party regulatory agencies are expected to emerge, but it’s still unclear who those will be. Before developers can build a safer and more efficient LLM for healthcare, they’ll need better guidelines and guardrails. “Unless we figure out evaluation, how would we know whether the healthcare-appropriate large language models are better or worse?” Shah asked.
 

A version of this article appeared on Medscape.com.

In seconds, Ravi Parikh, MD, an oncologist at the Emory University School of Medicine in Atlanta, had a summary of his patient’s entire medical history. Normally, Parikh skimmed the cumbersome files before seeing a patient. However, the artificial intelligence (AI) tool his institution was testing could list the highlights he needed in a fraction of the time.

“On the whole, I like it ... it saves me time,” Parikh said of the tool. “But I’d be lying if I told you it was perfect all the time. It’s interpreting the [patient] history in some ways that may be inaccurate,” he said.

Within the first week of testing the tool, Parikh started to notice that the large language model (LLM) made a particular mistake in his patients with prostate cancer. If their prostate-specific antigen test results came back slightly elevated — which is part of normal variation — the LLM recorded it as disease progression. Because Parikh reviews all his notes — with or without using an AI tool — after a visit, he easily caught the mistake before it was added to the chart. “The problem, I think, is if these mistakes go under the hood,” he said.

In the data science world, these mistakes are called hallucinations. And a growing body of research suggests they’re happening more frequently than is safe for healthcare. The industry promised LLMs would alleviate administrative burden and reduce physician burnout. But so far, studies show these AI-tool mistakes often create more work for doctors, not less. To truly help physicians and be safe for patients, some experts say healthcare needs to build its own LLMs from the ground up. And all agree that the field desperately needs a way to vet these algorithms more thoroughly.
 

Prone to Error

Right now, “I think the industry is focused on taking existing LLMs and forcing them into usage for healthcare,” said Nigam H. Shah, MBBS, PhD, chief data scientist for Stanford Health. However, the value of deploying general LLMs in the healthcare space is questionable. “People are starting to wonder if we’re using these tools wrong,” he told this news organization.

In 2023, Shah and his colleagues evaluated seven LLMs on their ability to answer electronic health record–based questions. For realistic tasks, the error rate in the best cases was about 35%, he said. “To me, that rate seems a bit high ... to adopt for routine use.”

A study earlier this year by the UC San Diego School of Medicine showed that using LLMs to respond to patient messages increased the time doctors spent on messages. And this summer, a study by the clinical AI firm Mendel found that when GPT-4o or Llama-3 were used to summarize patient medical records, almost every summary contained at least one type of hallucination.

“We’ve seen cases where a patient does have drug allergies, but the system says ‘no known drug allergies’ ” in the medical history summary, said Wael Salloum, PhD, cofounder and chief science officer at Mendel. “That’s a serious hallucination.” And if physicians have to constantly verify what the system is telling them, that “defeats the purpose [of summarization],” he said.
 

A Higher Quality Diet

Part of the trouble with LLMs is that there’s just not enough high-quality information to feed them. The algorithms are insatiable, requiring vast swaths of data for training. GPT-3.5, for instance, was trained on 570 GB of data from the internet, more than 300 billion words. And to train GPT-4o, OpenAI reportedly transcribed more than 1 million hours of YouTube content.

However, the strategies that built these general LLMs don’t always translate well to healthcare. The internet is full of low-quality or misleading health information from wellness sites and supplement advertisements. And even data that are trustworthy, like the millions of clinical studies and the US Food and Drug Administration (FDA) statements, can be outdated, Salloum said. And “an LLM in training can’t distinguish good from bad,” he added.

The good news is that clinicians don’t rely on controversial information in the real world. Medical knowledge is standardized. “Healthcare is a domain rich with explicit knowledge,” Salloum said. So there’s potential to build a more reliable LLM that is guided by robust medical standards and guidelines.

It’s possible that healthcare could use small language models, which are LLM’s pocket-sized cousins, and perform tasks needing only bite-sized datasets requiring fewer resources and easier fine-tuning, according to Microsoft’s website. Shah said training these smaller models on real medical data might be an option, like an LLM meant to respond to patient messages that could be trained with real messages sent by physicians.

Several groups are already working on databases of standardized human medical knowledge or real physician responses. “Perhaps that will work better than using LLMs trained on the general internet. Those studies need to be done,” Shah said.

Jon Tamir, assistant professor of electrical and computer engineering and co-lead of the AI Health Lab at The University of Texas at Austin, said, “The community has recognized that we are entering a new era of AI where the dataset itself is the most important aspect. We need training sets that are highly curated and highly specialized.

“If the dataset is highly specialized, it will definitely help reduce hallucinations,” he said.
 

Cutting Overconfidence

A major problem with LLM mistakes is that they are often hard to detect. Hallucinations can be highly convincing even if they’re highly inaccurate, according to Tamir.

When Shah, for instance, was recently testing an LLM on de-identified patient data, he asked the LLM which blood test the patient last had. The model responded with “complete blood count [CBC].” But when he asked for the results, the model gave him white blood count and other values. “Turns out that record did not have a CBC done at all! The result was entirely made up,” he said.

Making healthcare LLMs safer and more reliable will mean training AI to acknowledge potential mistakes and uncertainty. Existing LLMs are trained to project confidence and produce a lot of answers, even when there isn’t one, Salloum said. They rarely respond with “I don’t know” even when their prediction has low confidence, he added.

Healthcare stands to benefit from a system that highlights uncertainty and potential errors. For instance, if a patient’s history shows they have smoked, stopped smoking, vaped, and started smoking again. The LLM might call them a smoker but flag the comment as uncertain because the chronology is complicated, Salloum said.

Tamir added that this strategy could improve LLM and doctor collaboration by honing in on where human expertise is needed most.
 

Too Little Evaluation

For any improvement strategy to work, LLMs — and all AI-assisted healthcare tools — first need a better evaluation framework. So far, LLMs have “been used in really exciting ways but not really well-vetted ways,” Tamir said.

While some AI-assisted tools, particularly in medical imaging, have undergone rigorous FDA evaluations and earned approval, most haven’t. And because the FDA only regulates algorithms that are considered medical devices, Parikh said that most LLMs used for administrative tasks and efficiency don’t fall under the regulatory agency’s purview.

But these algorithms still have access to patient information and can directly influence patient and doctor decisions. Third-party regulatory agencies are expected to emerge, but it’s still unclear who those will be. Before developers can build a safer and more efficient LLM for healthcare, they’ll need better guidelines and guardrails. “Unless we figure out evaluation, how would we know whether the healthcare-appropriate large language models are better or worse?” Shah asked.
 

A version of this article appeared on Medscape.com.

From the largest healthcare companies to solo practices, just every organization in medicine faces a risk for costly cyberattacks. In recent years, hackers have threatened to release the personal information of patients and employees — or paralyze online systems — unless they’re paid a ransom.

Should companies pay? It’s not an easy answer, a pair of experts told colleagues in an American Medical Association (AMA) cybersecurity webinar on October 18. It turns out that each choice — pay or don’t pay — can end up being costly.

This is just one of the new challenges facing the American medical system on the cybersecurity front, the speakers said. Others include the possibility that hackers will manipulate patient data — turning a medical test negative, for example, when it’s actually positive — and take advantage of the powers of artificial intelligence (AI).

The AMA held the webinar to educate physicians about cybersecurity risks and defenses, an especially hot topic in the wake of February’s Change Healthcare hack, which cost UnitedHealth Group an estimated $2.5 billion — so far — and deeply disrupted the American healthcare system.

Cautionary tales abound. Greg Garcia, executive director for cybersecurity of the Health Sector Coordinating Council, a coalition of medical industry organizations, pointed to a Pennsylvania clinic that refused to pay a ransom to prevent the release of hundreds of images of patients with breast cancer undressed from the waist up. Garcia told webinar participants that the ransom was $5 million.
 

Risky Choices

While the Federal Bureau of Investigation recommends against paying a ransom, this can be a risky choice, Garcia said. Hackers released the images, and the center has reportedly agreed to settle a class-action lawsuit for $65 million. “They traded $5 million for $60 million,” Garcia added, slightly misstating the settlement amount.

Health systems have been cagey about whether they’ve paid ransoms to prevent private data from being made public in cyberattacks. If a ransom is demanded, “it’s every organization for itself,” Garcia said.

He highlighted the case of a chain of psychiatry practices in Finland that suffered a ransomware attack in 2020. The hackers “contacted the patients and said: ‘Hey, call your clinic and tell them to pay the ransom. Otherwise, we’re going to release all your psychiatric notes to the public.’ ”

Cyberattacks continue. In October, Boston Children’s Health Physicians announced that it had suffered a “ recent security incident” involving data — possibly including Social Security numbers and treatment information — regarding patients and employees. A hacker group reportedly claimed responsibility and wants the system, which boasts more than 300 clinicians, to pay a ransom or else it will release the stolen information.
 

Should Paying Ransom Be a Crime?

Christian Dameff, MD, MS, an emergency medicine physician and director of the Center for Healthcare Cybersecurity at the University of California (UC), San Diego, noted that there are efforts to turn paying ransom into a crime. “If people aren’t paying ransoms, then ransomware operators will move to something else that makes them money.”

Dameff urged colleagues to understand we no longer live in a world where clinicians only bother to think of technology when they call the IT department to help them reset their password.

New challenges face clinicians, he said. “How do we develop better strategies, downtime procedures, and safe clinical care in an era where our vital technology may be gone, not just for an hour or 2, but as is the case with these ransomware attacks, sometimes weeks to months.”

Garcia said “cybersecurity is everybody’s responsibility, including frontline clinicians. Because you’re touching data, you’re touching technology, you’re touching patients, and all of those things combine to present some vulnerabilities in the digital world.”
 

Next Frontier: Hackers May Manipulate Patient Data

Dameff said future hackers may use AI to manipulate individual patient data in ways that threaten patient health. AI makes this easier to accomplish.

“What if I delete your allergies in your electronic health record, or I manipulate your chest x-ray, or I change your lab values so it looks like you’re in diabetic ketoacidosis when you’re not so a clinician gives you insulin when you don’t need it?”

Garcia highlighted another new threat: Phishing efforts that are harder to ignore thanks to AI.

“One of the most successful way that hackers get in, disrupt systems, and steal data is through email phishing, and it’s only going to get better because of artificial intelligence,” he said. “No longer are you going to have typos in that email written by a hacking group in Nigeria or in China. It’s going to be perfect looking.”

What can practices and healthcare systems do? Garcia highlighted federal health agency efforts to encourage organizations to adopt best practices in cybersecurity.

“If you’ve got a data breach, and you can show to the US Department of Health & Human Services [HHS] you have implemented generally recognized cybersecurity controls over the past year, that you have done your best, you did the right thing, and you still got hit, HHS is directed to essentially take it easy on you,” he said. “That’s a positive incentive.”
 

Ransomware Guide in the Works

Dameff said UC San Diego’s Center for Healthcare Cybersecurity plans to publish a free cybersecurity guide in 2025 that will include specific information about ransomware attacks for medical specialties such as cardiology, trauma surgery, and pediatrics.

“Then, should you ever be ransomed, you can pull out this guide. You’ll know what’s going to kind of happen, and you can better prepare for those effects.”

Will the future president prioritize healthcare cybersecurity? That remains to be seen, but crises do have the capacity to concentrate the mind, experts said.

The nation’s capital “has a very short memory, a short attention span. The policymakers tend to be reactive,” Dameff said. “All it takes is yet another Change Healthcare–like attack that disrupts 30% or more of the nation’s healthcare system for the policymakers to sit up, take notice, and try to come up with solutions.”

In addition, he said, an estimated two data breaches/ransomware attacks are occurring per day. “The fact is that we’re all patients, up to the President of the United States and every member of the Congress is a patient.”

There’s a “very existential, very palpable understanding that cyber safety is patient safety and cyber insecurity is patient insecurity,” Dameff said.

A version of this article appeared on Medscape.com.

From the largest healthcare companies to solo practices, just every organization in medicine faces a risk for costly cyberattacks. In recent years, hackers have threatened to release the personal information of patients and employees — or paralyze online systems — unless they’re paid a ransom.

Should companies pay? It’s not an easy answer, a pair of experts told colleagues in an American Medical Association (AMA) cybersecurity webinar on October 18. It turns out that each choice — pay or don’t pay — can end up being costly.

This is just one of the new challenges facing the American medical system on the cybersecurity front, the speakers said. Others include the possibility that hackers will manipulate patient data — turning a medical test negative, for example, when it’s actually positive — and take advantage of the powers of artificial intelligence (AI).

The AMA held the webinar to educate physicians about cybersecurity risks and defenses, an especially hot topic in the wake of February’s Change Healthcare hack, which cost UnitedHealth Group an estimated $2.5 billion — so far — and deeply disrupted the American healthcare system.

Cautionary tales abound. Greg Garcia, executive director for cybersecurity of the Health Sector Coordinating Council, a coalition of medical industry organizations, pointed to a Pennsylvania clinic that refused to pay a ransom to prevent the release of hundreds of images of patients with breast cancer undressed from the waist up. Garcia told webinar participants that the ransom was $5 million.
 

Risky Choices

While the Federal Bureau of Investigation recommends against paying a ransom, this can be a risky choice, Garcia said. Hackers released the images, and the center has reportedly agreed to settle a class-action lawsuit for $65 million. “They traded $5 million for $60 million,” Garcia added, slightly misstating the settlement amount.

Health systems have been cagey about whether they’ve paid ransoms to prevent private data from being made public in cyberattacks. If a ransom is demanded, “it’s every organization for itself,” Garcia said.

He highlighted the case of a chain of psychiatry practices in Finland that suffered a ransomware attack in 2020. The hackers “contacted the patients and said: ‘Hey, call your clinic and tell them to pay the ransom. Otherwise, we’re going to release all your psychiatric notes to the public.’ ”

Cyberattacks continue. In October, Boston Children’s Health Physicians announced that it had suffered a “ recent security incident” involving data — possibly including Social Security numbers and treatment information — regarding patients and employees. A hacker group reportedly claimed responsibility and wants the system, which boasts more than 300 clinicians, to pay a ransom or else it will release the stolen information.
 

Should Paying Ransom Be a Crime?

Christian Dameff, MD, MS, an emergency medicine physician and director of the Center for Healthcare Cybersecurity at the University of California (UC), San Diego, noted that there are efforts to turn paying ransom into a crime. “If people aren’t paying ransoms, then ransomware operators will move to something else that makes them money.”

Dameff urged colleagues to understand we no longer live in a world where clinicians only bother to think of technology when they call the IT department to help them reset their password.

New challenges face clinicians, he said. “How do we develop better strategies, downtime procedures, and safe clinical care in an era where our vital technology may be gone, not just for an hour or 2, but as is the case with these ransomware attacks, sometimes weeks to months.”

Garcia said “cybersecurity is everybody’s responsibility, including frontline clinicians. Because you’re touching data, you’re touching technology, you’re touching patients, and all of those things combine to present some vulnerabilities in the digital world.”
 

Next Frontier: Hackers May Manipulate Patient Data

Dameff said future hackers may use AI to manipulate individual patient data in ways that threaten patient health. AI makes this easier to accomplish.

“What if I delete your allergies in your electronic health record, or I manipulate your chest x-ray, or I change your lab values so it looks like you’re in diabetic ketoacidosis when you’re not so a clinician gives you insulin when you don’t need it?”

Garcia highlighted another new threat: Phishing efforts that are harder to ignore thanks to AI.

“One of the most successful way that hackers get in, disrupt systems, and steal data is through email phishing, and it’s only going to get better because of artificial intelligence,” he said. “No longer are you going to have typos in that email written by a hacking group in Nigeria or in China. It’s going to be perfect looking.”

What can practices and healthcare systems do? Garcia highlighted federal health agency efforts to encourage organizations to adopt best practices in cybersecurity.

“If you’ve got a data breach, and you can show to the US Department of Health & Human Services [HHS] you have implemented generally recognized cybersecurity controls over the past year, that you have done your best, you did the right thing, and you still got hit, HHS is directed to essentially take it easy on you,” he said. “That’s a positive incentive.”
 

Ransomware Guide in the Works

Dameff said UC San Diego’s Center for Healthcare Cybersecurity plans to publish a free cybersecurity guide in 2025 that will include specific information about ransomware attacks for medical specialties such as cardiology, trauma surgery, and pediatrics.

“Then, should you ever be ransomed, you can pull out this guide. You’ll know what’s going to kind of happen, and you can better prepare for those effects.”

Will the future president prioritize healthcare cybersecurity? That remains to be seen, but crises do have the capacity to concentrate the mind, experts said.

The nation’s capital “has a very short memory, a short attention span. The policymakers tend to be reactive,” Dameff said. “All it takes is yet another Change Healthcare–like attack that disrupts 30% or more of the nation’s healthcare system for the policymakers to sit up, take notice, and try to come up with solutions.”

In addition, he said, an estimated two data breaches/ransomware attacks are occurring per day. “The fact is that we’re all patients, up to the President of the United States and every member of the Congress is a patient.”

There’s a “very existential, very palpable understanding that cyber safety is patient safety and cyber insecurity is patient insecurity,” Dameff said.

A version of this article appeared on Medscape.com.

From the largest healthcare companies to solo practices, just every organization in medicine faces a risk for costly cyberattacks. In recent years, hackers have threatened to release the personal information of patients and employees — or paralyze online systems — unless they’re paid a ransom.

Should companies pay? It’s not an easy answer, a pair of experts told colleagues in an American Medical Association (AMA) cybersecurity webinar on October 18. It turns out that each choice — pay or don’t pay — can end up being costly.

This is just one of the new challenges facing the American medical system on the cybersecurity front, the speakers said. Others include the possibility that hackers will manipulate patient data — turning a medical test negative, for example, when it’s actually positive — and take advantage of the powers of artificial intelligence (AI).

The AMA held the webinar to educate physicians about cybersecurity risks and defenses, an especially hot topic in the wake of February’s Change Healthcare hack, which cost UnitedHealth Group an estimated $2.5 billion — so far — and deeply disrupted the American healthcare system.

Cautionary tales abound. Greg Garcia, executive director for cybersecurity of the Health Sector Coordinating Council, a coalition of medical industry organizations, pointed to a Pennsylvania clinic that refused to pay a ransom to prevent the release of hundreds of images of patients with breast cancer undressed from the waist up. Garcia told webinar participants that the ransom was $5 million.
 

Risky Choices

While the Federal Bureau of Investigation recommends against paying a ransom, this can be a risky choice, Garcia said. Hackers released the images, and the center has reportedly agreed to settle a class-action lawsuit for $65 million. “They traded $5 million for $60 million,” Garcia added, slightly misstating the settlement amount.

Health systems have been cagey about whether they’ve paid ransoms to prevent private data from being made public in cyberattacks. If a ransom is demanded, “it’s every organization for itself,” Garcia said.

He highlighted the case of a chain of psychiatry practices in Finland that suffered a ransomware attack in 2020. The hackers “contacted the patients and said: ‘Hey, call your clinic and tell them to pay the ransom. Otherwise, we’re going to release all your psychiatric notes to the public.’ ”

Cyberattacks continue. In October, Boston Children’s Health Physicians announced that it had suffered a “ recent security incident” involving data — possibly including Social Security numbers and treatment information — regarding patients and employees. A hacker group reportedly claimed responsibility and wants the system, which boasts more than 300 clinicians, to pay a ransom or else it will release the stolen information.
 

Should Paying Ransom Be a Crime?

Christian Dameff, MD, MS, an emergency medicine physician and director of the Center for Healthcare Cybersecurity at the University of California (UC), San Diego, noted that there are efforts to turn paying ransom into a crime. “If people aren’t paying ransoms, then ransomware operators will move to something else that makes them money.”

Dameff urged colleagues to understand we no longer live in a world where clinicians only bother to think of technology when they call the IT department to help them reset their password.

New challenges face clinicians, he said. “How do we develop better strategies, downtime procedures, and safe clinical care in an era where our vital technology may be gone, not just for an hour or 2, but as is the case with these ransomware attacks, sometimes weeks to months.”

Garcia said “cybersecurity is everybody’s responsibility, including frontline clinicians. Because you’re touching data, you’re touching technology, you’re touching patients, and all of those things combine to present some vulnerabilities in the digital world.”
 

Next Frontier: Hackers May Manipulate Patient Data

Dameff said future hackers may use AI to manipulate individual patient data in ways that threaten patient health. AI makes this easier to accomplish.

“What if I delete your allergies in your electronic health record, or I manipulate your chest x-ray, or I change your lab values so it looks like you’re in diabetic ketoacidosis when you’re not so a clinician gives you insulin when you don’t need it?”

Garcia highlighted another new threat: Phishing efforts that are harder to ignore thanks to AI.

“One of the most successful way that hackers get in, disrupt systems, and steal data is through email phishing, and it’s only going to get better because of artificial intelligence,” he said. “No longer are you going to have typos in that email written by a hacking group in Nigeria or in China. It’s going to be perfect looking.”

What can practices and healthcare systems do? Garcia highlighted federal health agency efforts to encourage organizations to adopt best practices in cybersecurity.

“If you’ve got a data breach, and you can show to the US Department of Health & Human Services [HHS] you have implemented generally recognized cybersecurity controls over the past year, that you have done your best, you did the right thing, and you still got hit, HHS is directed to essentially take it easy on you,” he said. “That’s a positive incentive.”
 

Ransomware Guide in the Works

Dameff said UC San Diego’s Center for Healthcare Cybersecurity plans to publish a free cybersecurity guide in 2025 that will include specific information about ransomware attacks for medical specialties such as cardiology, trauma surgery, and pediatrics.

“Then, should you ever be ransomed, you can pull out this guide. You’ll know what’s going to kind of happen, and you can better prepare for those effects.”

Will the future president prioritize healthcare cybersecurity? That remains to be seen, but crises do have the capacity to concentrate the mind, experts said.

The nation’s capital “has a very short memory, a short attention span. The policymakers tend to be reactive,” Dameff said. “All it takes is yet another Change Healthcare–like attack that disrupts 30% or more of the nation’s healthcare system for the policymakers to sit up, take notice, and try to come up with solutions.”

In addition, he said, an estimated two data breaches/ransomware attacks are occurring per day. “The fact is that we’re all patients, up to the President of the United States and every member of the Congress is a patient.”

There’s a “very existential, very palpable understanding that cyber safety is patient safety and cyber insecurity is patient insecurity,” Dameff said.

A version of this article appeared on Medscape.com.

TOPLINE:

Stroke rates in Californians with sickle cell disease (SCD) have increased in both children and adults in the post-STOP era. The cumulative incidence of first ischemic stroke was 2.1% by age 20 and 13.5% by age 60.

METHODOLOGY:

• Researchers analyzed data from the California Department of Health Care Access and Innovation (HCAI), covering emergency department and hospitalization records from 1991 to 2019.
• A total of 7636 patients with SCD were included in the study cohort.
• Cumulative incidence and rates for primary and recurrent strokes and transient ischemic attacks (TIAs) were determined pre- and post STOP trial.
• Patients with SCD were identified using ICD-9 and ICD-10 codes, with specific criteria for inclusion based on hospitalization records.
• The study utilized Fine and Gray methodology to calculate cumulative incidence functions, accounting for the competing risk for death.

TAKEAWAY:

• The cumulative incidence of first ischemic stroke in patients with SCD was 2.1% by age 20 and 13.5% by age 60.
• Ischemic stroke rates increased significantly in children and adults in the 2010-2019 period, compared with the preceding decade.
• Risk factors for stroke and TIA included increasing age, hypertension, and hyperlipidemia.
• The study found a significant increase in rates of intracranial hemorrhage in adults aged 18-30 years and TIAs in children younger than 18 years from 2010 to 2019, compared with the prior decade.

IN PRACTICE:

“Neurovascular complications, including strokes and transient ischemic attacks (TIAs), are common and cause significant morbidity in individuals with sickle cell disease (SCD). The STOP trial (1998) established chronic transfusions as the standard of care for children with SCD at high risk for stroke,” the study’s authors wrote.

SOURCE:

This study was led by Olubusola B. Oluwole, MD, MS, University of Pittsburgh in Pennsylvania, and was published online in Blood.

LIMITATIONS:

This study’s reliance on administrative data may have introduced systematic errors, particularly with the transition from ICD-9 to ICD-10 codes. The lack of laboratory results and medication data in the HCAI database limited the ability to fully assess patient conditions and treatments. Additionally, the methodology changes in 2014 likely underreported death rates in people without PDD/EDU encounters in the calendar year preceding their death.

DISCLOSURES:

The authors reported no relevant conflicts of interest.

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

TOPLINE:

Stroke rates in Californians with sickle cell disease (SCD) have increased in both children and adults in the post-STOP era. The cumulative incidence of first ischemic stroke was 2.1% by age 20 and 13.5% by age 60.

METHODOLOGY:

• Researchers analyzed data from the California Department of Health Care Access and Innovation (HCAI), covering emergency department and hospitalization records from 1991 to 2019.
• A total of 7636 patients with SCD were included in the study cohort.
• Cumulative incidence and rates for primary and recurrent strokes and transient ischemic attacks (TIAs) were determined pre- and post STOP trial.
• Patients with SCD were identified using ICD-9 and ICD-10 codes, with specific criteria for inclusion based on hospitalization records.
• The study utilized Fine and Gray methodology to calculate cumulative incidence functions, accounting for the competing risk for death.

TAKEAWAY:

• The cumulative incidence of first ischemic stroke in patients with SCD was 2.1% by age 20 and 13.5% by age 60.
• Ischemic stroke rates increased significantly in children and adults in the 2010-2019 period, compared with the preceding decade.
• Risk factors for stroke and TIA included increasing age, hypertension, and hyperlipidemia.
• The study found a significant increase in rates of intracranial hemorrhage in adults aged 18-30 years and TIAs in children younger than 18 years from 2010 to 2019, compared with the prior decade.

IN PRACTICE:

“Neurovascular complications, including strokes and transient ischemic attacks (TIAs), are common and cause significant morbidity in individuals with sickle cell disease (SCD). The STOP trial (1998) established chronic transfusions as the standard of care for children with SCD at high risk for stroke,” the study’s authors wrote.

SOURCE:

This study was led by Olubusola B. Oluwole, MD, MS, University of Pittsburgh in Pennsylvania, and was published online in Blood.

LIMITATIONS:

This study’s reliance on administrative data may have introduced systematic errors, particularly with the transition from ICD-9 to ICD-10 codes. The lack of laboratory results and medication data in the HCAI database limited the ability to fully assess patient conditions and treatments. Additionally, the methodology changes in 2014 likely underreported death rates in people without PDD/EDU encounters in the calendar year preceding their death.

DISCLOSURES:

The authors reported no relevant conflicts of interest.

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

TOPLINE:

Stroke rates in Californians with sickle cell disease (SCD) have increased in both children and adults in the post-STOP era. The cumulative incidence of first ischemic stroke was 2.1% by age 20 and 13.5% by age 60.

METHODOLOGY:

• Researchers analyzed data from the California Department of Health Care Access and Innovation (HCAI), covering emergency department and hospitalization records from 1991 to 2019.
• A total of 7636 patients with SCD were included in the study cohort.
• Cumulative incidence and rates for primary and recurrent strokes and transient ischemic attacks (TIAs) were determined pre- and post STOP trial.
• Patients with SCD were identified using ICD-9 and ICD-10 codes, with specific criteria for inclusion based on hospitalization records.
• The study utilized Fine and Gray methodology to calculate cumulative incidence functions, accounting for the competing risk for death.

TAKEAWAY:

• The cumulative incidence of first ischemic stroke in patients with SCD was 2.1% by age 20 and 13.5% by age 60.
• Ischemic stroke rates increased significantly in children and adults in the 2010-2019 period, compared with the preceding decade.
• Risk factors for stroke and TIA included increasing age, hypertension, and hyperlipidemia.
• The study found a significant increase in rates of intracranial hemorrhage in adults aged 18-30 years and TIAs in children younger than 18 years from 2010 to 2019, compared with the prior decade.

IN PRACTICE:

“Neurovascular complications, including strokes and transient ischemic attacks (TIAs), are common and cause significant morbidity in individuals with sickle cell disease (SCD). The STOP trial (1998) established chronic transfusions as the standard of care for children with SCD at high risk for stroke,” the study’s authors wrote.

SOURCE:

This study was led by Olubusola B. Oluwole, MD, MS, University of Pittsburgh in Pennsylvania, and was published online in Blood.

LIMITATIONS:

This study’s reliance on administrative data may have introduced systematic errors, particularly with the transition from ICD-9 to ICD-10 codes. The lack of laboratory results and medication data in the HCAI database limited the ability to fully assess patient conditions and treatments. Additionally, the methodology changes in 2014 likely underreported death rates in people without PDD/EDU encounters in the calendar year preceding their death.

DISCLOSURES:

The authors reported no relevant conflicts of interest.

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

ABU DHABI, UAE — The long-standing debate as to when to start anticoagulation in patients with an acute ischemic stroke and atrial fibrillation (AF) looks as though it’s settled.

Results of the OPTIMAS trial, the largest trial to address this question, showed that initiation of a direct oral anticoagulant (DOAC) within 4 days after ischemic stroke associated with AF was noninferior to delayed initiation (7-14 days) for the composite outcome of ischemic stroke, intracranial hemorrhage, unclassifiable stroke, or systemic embolism at 90 days. Importantly, early DOAC initiation was safe with a low rate of symptomatic hemorrhage, regardless of stroke severity.

In addition, a new meta-analysis, known as CATALYST, which included all four randomized trials now available on this issue, showed a clear benefit of earlier initiation (within 4 days) versus later (5 days and up) on its primary endpoint of new ischemic stroke, symptomatic intracerebral hemorrhage, and unclassified stroke at 30 days.

The results of the OPTIMAS trial and the meta-analysis were both presented at the 16th World Stroke Congress (WSC) 2024. The OPTIMAS trial was also simultaneously published online in The Lancet.

“Our findings do not support the guideline recommended practice of delaying DOAC initiation after ischemic stroke with AF regardless of clinical stroke severity, reperfusion or prior anticoagulation,” said OPTIMAS investigator David Werring, PhD, University College London in England.

Presenting the meta-analysis, Signild Åsberg, MD, Uppsala University, Uppsala, Sweden, said his group’s findings “support the early start of DOACs (within 4 days) in clinical practice.”

Werring pointed out that starting anticoagulation early also had important logistical advantages.

“This means we can start anticoagulation before patients are discharged from hospital, thus ensuring that this important secondary prevention medication is always prescribed, when appropriate. That’s going to be a key benefit in the real world.”
 

Clinical Dilemma

Werring noted that AF accounts for 20%-30% of ischemic strokes, which tend to be more severe than other stroke types. The pivotal trials of DOACs did not include patients within 30 days of an acute ischemic stroke, creating a clinical dilemma on when to start this treatment.

“On the one hand, we wish to start anticoagulation early to reduce early recurrence of ischemic stroke. But on the other hand, there are concerns that if we start anticoagulation early, it could cause intracranial bleeding, including hemorrhagic transformation of the acute infarct. Guidelines on this issue are inconsistent and have called for randomized control trials in this area,” he noted.

So far, three randomized trials on DOAC timing have been conducted, which Werring said suggested early DOAC treatment is safe. However, these trials have provided limited data on moderate to severe stroke, patients with hemorrhagic transformation, or those already taking oral anticoagulants — subgroups in which there are particular concerns about early oral anticoagulation.

The OPTIMAS trial included a broad population of patients with acute ischemic stroke associated with AF including these critical subgroups.

The trial, conducted at 100 hospitals in the United Kingdom, included 3648 patients with AF and acute ischemic stroke who were randomly assigned to early (≤ 4 days from stroke symptom onset) or delayed (7-14 days) anticoagulation initiation with any DOAC.

There was no restriction on stroke severity, and patients with hemorrhagic transformation were allowed, with the exception of parenchymal hematoma type 2, a rare and severe type of hemorrhagic transformation.

Approximately 35% of patients had been taking an oral anticoagulant, mainly DOACs, prior to their stroke, and about 30% had revascularization with thrombolysis, thrombectomy, or both. Nearly 900 participants (25%) had moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥ 11).

The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days. The initial analysis aimed to show noninferiority of early DOAC initiation, with a noninferiority margin of 2 percentage points, followed by testing for superiority.

Results showed that the primary outcome occurred in 3.3% of both groups (adjusted risk difference, 0.000; 95% CI, −0.011 to 0.012), with noninferiority criteria fulfilled. Superiority was not achieved.

Symptomatic intracranial hemorrhage occurred in 0.6% of patients in the early DOAC initiation group vs 0.7% of those in the delayed group — a nonsignificant difference.
 

Applicable to Real-World Practice

A time-to-event analysis of the primary outcome showed that there were fewer outcomes in the first 30 days in the early DOAC initiation group, but the curves subsequently came together.

Subgroup analysis showed consistent results across all whole trial population, with no modification of the effect of early DOAC initiation according to stroke severity, reperfusion treatment, or previous anticoagulation.

Werring said that strengths of the OPTIMAS trial included a large sample size, a broad population with generalizability to real-world practice, and the inclusion of patients at higher bleeding risk than included in previous studies.

During the discussion, it was noted that the trial included few (about 3%) patients — about 3% — with very severe stroke (NIHSS score > 21), with the question of whether the findings could be applied to this group.

Werring noted that there was no evidence of heterogeneity, and if anything, patients with more severe strokes may have had a slightly greater benefit with early DOAC initiation. “So my feeling is probably these results do generalize to the more severe patients,” he said.

In a commentary accompanying The Lancet publication of the OPTIMAS trial, Else Charlotte Sandset, MD, University of Oslo, in Norway, and Diana Aguiar de Sousa, MD, Central Lisbon University Hospital Centre, Lisbon, Portugal, noted that the “increasing body of evidence strongly supports the message that initiating anticoagulation early for patients with ischaemic stroke is safe. The consistent absence of heterogeneity in safety outcomes suggests that the risk of symptomatic intracranial haemorrhage is not a major concern, even in patients with large infarcts.”

Regardless of the size of the treatment effect, initiating early anticoagulation makes sense when it can be done safely, as it helps prevent recurrent ischemic strokes and other embolic events. Early intervention reduces embolization risk, particularly in high-risk patients, and allows secondary prevention measures to begin while patients are still hospitalized, they added.
 

CATALYST Findings

The CATALYST meta-analysis included four trials, namely, TIMING, ELAN, OPTIMAS, and START, of early versus later DOAC administration in a total of 5411 patients with acute ischemic stroke and AF. In this meta-analysis, early was defined as within 4 days of stroke and later as 5 days or more.

The primary outcome was a composite of ischemic stroke, symptomatic, intracerebral hemorrhage, or unclassified stroke at 30 days. This was significantly reduced in the early group (2.12%) versus 3.02% in the later group, giving an odds ratio of 0.70 (95% CI, 0.50-0.98; P =.04).

The results were consistent across all subgroups, all suggesting an advantage for early DOAC.

Further analysis showed a clear benefit of early DOAC initiation in ischemic stroke with the curves separating early.

The rate of symptomatic intracerebral hemorrhage was low in both groups (0.45% in the early group and 0.40% in the later group) as was extracranial hemorrhage (0.45% vs 0.55%).

At 90 days, there were still lower event rates in the early group than the later one, but the difference was no longer statistically significant.
 

‘Practice Changing’ Results

Commenting on both studies, chair of the WSC session where the results of both OPTIMAS trial and the meta-analysis were presented, Craig Anderson, MD, The George Institute for Global Health, Sydney, Australia, described these latest results as “practice changing.”

“When to start anticoagulation in acute ischemic stroke patients with AF has been uncertain for a long time. The dogma has always been that we should wait. Over the years, we’ve become a little bit more confident, but now we’ve got good data from randomized trials showing that early initiation is safe, with the meta-analysis showing benefit,” he said.

“These new data from OPTIMAS will reassure clinicians that there’s no excessive harm and, more importantly, no excessive harm across all patient groups. And the meta-analysis clearly showed an upfront benefit of starting anticoagulation early. That’s a very convincing result,” he added.

Anderson cautioned that there still may be concerns about starting DOACs early in some groups, including Asian populations that have a higher bleeding risk (these trials included predominantly White patients) and people who are older or frail, who may have extensive small vessel disease.

During the discussion, several questions centered on the lack of imaging data available on the patients in the studies. Anderson said imaging data would help reassure clinicians on the safety of early anticoagulation in patients with large infarcts.

“Stroke clinicians make decisions on the basis of the patient and on the basis of the brain, and we only have the patient information at the moment. We don’t have information on the brain — that comes from imaging.”

Regardless, he believes these new data will lead to a shift in practice. “But maybe, it won’t be as dramatic as we would hope because I think some clinicians may still hesitate to apply these results to patients at high risk of bleeding. With imaging data from the studies that might change.”

The OPTIMAS trial was funded by University College London and the British Heart Foundation. Werring reported consulting fees from Novo Nordisk, National Institute for Health and Care Excellence, and Alnylam; payments or speaker honoraria from Novo Nordisk, Bayer, and AstraZeneca/Alexion; participation on a data safety monitoring board for the OXHARP trial; and participation as steering committee chair for the MACE-ICH and PLINTH trials. Åsberg received institutional research grants and lecture fees to her institution from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Institut Produits Synthése. Sandset and de Sousa were both steering committee members of the ELAN trial. Anderson reported grant funding from Penumbra and Takeda China.
 

A version of this article appeared on Medscape.com.

ABU DHABI, UAE — The long-standing debate as to when to start anticoagulation in patients with an acute ischemic stroke and atrial fibrillation (AF) looks as though it’s settled.

Results of the OPTIMAS trial, the largest trial to address this question, showed that initiation of a direct oral anticoagulant (DOAC) within 4 days after ischemic stroke associated with AF was noninferior to delayed initiation (7-14 days) for the composite outcome of ischemic stroke, intracranial hemorrhage, unclassifiable stroke, or systemic embolism at 90 days. Importantly, early DOAC initiation was safe with a low rate of symptomatic hemorrhage, regardless of stroke severity.

In addition, a new meta-analysis, known as CATALYST, which included all four randomized trials now available on this issue, showed a clear benefit of earlier initiation (within 4 days) versus later (5 days and up) on its primary endpoint of new ischemic stroke, symptomatic intracerebral hemorrhage, and unclassified stroke at 30 days.

The results of the OPTIMAS trial and the meta-analysis were both presented at the 16th World Stroke Congress (WSC) 2024. The OPTIMAS trial was also simultaneously published online in The Lancet.

“Our findings do not support the guideline recommended practice of delaying DOAC initiation after ischemic stroke with AF regardless of clinical stroke severity, reperfusion or prior anticoagulation,” said OPTIMAS investigator David Werring, PhD, University College London in England.

Presenting the meta-analysis, Signild Åsberg, MD, Uppsala University, Uppsala, Sweden, said his group’s findings “support the early start of DOACs (within 4 days) in clinical practice.”

Werring pointed out that starting anticoagulation early also had important logistical advantages.

“This means we can start anticoagulation before patients are discharged from hospital, thus ensuring that this important secondary prevention medication is always prescribed, when appropriate. That’s going to be a key benefit in the real world.”
 

Clinical Dilemma

Werring noted that AF accounts for 20%-30% of ischemic strokes, which tend to be more severe than other stroke types. The pivotal trials of DOACs did not include patients within 30 days of an acute ischemic stroke, creating a clinical dilemma on when to start this treatment.

“On the one hand, we wish to start anticoagulation early to reduce early recurrence of ischemic stroke. But on the other hand, there are concerns that if we start anticoagulation early, it could cause intracranial bleeding, including hemorrhagic transformation of the acute infarct. Guidelines on this issue are inconsistent and have called for randomized control trials in this area,” he noted.

So far, three randomized trials on DOAC timing have been conducted, which Werring said suggested early DOAC treatment is safe. However, these trials have provided limited data on moderate to severe stroke, patients with hemorrhagic transformation, or those already taking oral anticoagulants — subgroups in which there are particular concerns about early oral anticoagulation.

The OPTIMAS trial included a broad population of patients with acute ischemic stroke associated with AF including these critical subgroups.

The trial, conducted at 100 hospitals in the United Kingdom, included 3648 patients with AF and acute ischemic stroke who were randomly assigned to early (≤ 4 days from stroke symptom onset) or delayed (7-14 days) anticoagulation initiation with any DOAC.

There was no restriction on stroke severity, and patients with hemorrhagic transformation were allowed, with the exception of parenchymal hematoma type 2, a rare and severe type of hemorrhagic transformation.

Approximately 35% of patients had been taking an oral anticoagulant, mainly DOACs, prior to their stroke, and about 30% had revascularization with thrombolysis, thrombectomy, or both. Nearly 900 participants (25%) had moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥ 11).

The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days. The initial analysis aimed to show noninferiority of early DOAC initiation, with a noninferiority margin of 2 percentage points, followed by testing for superiority.

Results showed that the primary outcome occurred in 3.3% of both groups (adjusted risk difference, 0.000; 95% CI, −0.011 to 0.012), with noninferiority criteria fulfilled. Superiority was not achieved.

Symptomatic intracranial hemorrhage occurred in 0.6% of patients in the early DOAC initiation group vs 0.7% of those in the delayed group — a nonsignificant difference.
 

Applicable to Real-World Practice

A time-to-event analysis of the primary outcome showed that there were fewer outcomes in the first 30 days in the early DOAC initiation group, but the curves subsequently came together.

Subgroup analysis showed consistent results across all whole trial population, with no modification of the effect of early DOAC initiation according to stroke severity, reperfusion treatment, or previous anticoagulation.

Werring said that strengths of the OPTIMAS trial included a large sample size, a broad population with generalizability to real-world practice, and the inclusion of patients at higher bleeding risk than included in previous studies.

During the discussion, it was noted that the trial included few (about 3%) patients — about 3% — with very severe stroke (NIHSS score > 21), with the question of whether the findings could be applied to this group.

Werring noted that there was no evidence of heterogeneity, and if anything, patients with more severe strokes may have had a slightly greater benefit with early DOAC initiation. “So my feeling is probably these results do generalize to the more severe patients,” he said.

In a commentary accompanying The Lancet publication of the OPTIMAS trial, Else Charlotte Sandset, MD, University of Oslo, in Norway, and Diana Aguiar de Sousa, MD, Central Lisbon University Hospital Centre, Lisbon, Portugal, noted that the “increasing body of evidence strongly supports the message that initiating anticoagulation early for patients with ischaemic stroke is safe. The consistent absence of heterogeneity in safety outcomes suggests that the risk of symptomatic intracranial haemorrhage is not a major concern, even in patients with large infarcts.”

Regardless of the size of the treatment effect, initiating early anticoagulation makes sense when it can be done safely, as it helps prevent recurrent ischemic strokes and other embolic events. Early intervention reduces embolization risk, particularly in high-risk patients, and allows secondary prevention measures to begin while patients are still hospitalized, they added.
 

CATALYST Findings

The CATALYST meta-analysis included four trials, namely, TIMING, ELAN, OPTIMAS, and START, of early versus later DOAC administration in a total of 5411 patients with acute ischemic stroke and AF. In this meta-analysis, early was defined as within 4 days of stroke and later as 5 days or more.

The primary outcome was a composite of ischemic stroke, symptomatic, intracerebral hemorrhage, or unclassified stroke at 30 days. This was significantly reduced in the early group (2.12%) versus 3.02% in the later group, giving an odds ratio of 0.70 (95% CI, 0.50-0.98; P =.04).

The results were consistent across all subgroups, all suggesting an advantage for early DOAC.

Further analysis showed a clear benefit of early DOAC initiation in ischemic stroke with the curves separating early.

The rate of symptomatic intracerebral hemorrhage was low in both groups (0.45% in the early group and 0.40% in the later group) as was extracranial hemorrhage (0.45% vs 0.55%).

At 90 days, there were still lower event rates in the early group than the later one, but the difference was no longer statistically significant.
 

‘Practice Changing’ Results

Commenting on both studies, chair of the WSC session where the results of both OPTIMAS trial and the meta-analysis were presented, Craig Anderson, MD, The George Institute for Global Health, Sydney, Australia, described these latest results as “practice changing.”

“When to start anticoagulation in acute ischemic stroke patients with AF has been uncertain for a long time. The dogma has always been that we should wait. Over the years, we’ve become a little bit more confident, but now we’ve got good data from randomized trials showing that early initiation is safe, with the meta-analysis showing benefit,” he said.

“These new data from OPTIMAS will reassure clinicians that there’s no excessive harm and, more importantly, no excessive harm across all patient groups. And the meta-analysis clearly showed an upfront benefit of starting anticoagulation early. That’s a very convincing result,” he added.

Anderson cautioned that there still may be concerns about starting DOACs early in some groups, including Asian populations that have a higher bleeding risk (these trials included predominantly White patients) and people who are older or frail, who may have extensive small vessel disease.

During the discussion, several questions centered on the lack of imaging data available on the patients in the studies. Anderson said imaging data would help reassure clinicians on the safety of early anticoagulation in patients with large infarcts.

“Stroke clinicians make decisions on the basis of the patient and on the basis of the brain, and we only have the patient information at the moment. We don’t have information on the brain — that comes from imaging.”

Regardless, he believes these new data will lead to a shift in practice. “But maybe, it won’t be as dramatic as we would hope because I think some clinicians may still hesitate to apply these results to patients at high risk of bleeding. With imaging data from the studies that might change.”

The OPTIMAS trial was funded by University College London and the British Heart Foundation. Werring reported consulting fees from Novo Nordisk, National Institute for Health and Care Excellence, and Alnylam; payments or speaker honoraria from Novo Nordisk, Bayer, and AstraZeneca/Alexion; participation on a data safety monitoring board for the OXHARP trial; and participation as steering committee chair for the MACE-ICH and PLINTH trials. Åsberg received institutional research grants and lecture fees to her institution from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Institut Produits Synthése. Sandset and de Sousa were both steering committee members of the ELAN trial. Anderson reported grant funding from Penumbra and Takeda China.
 

A version of this article appeared on Medscape.com.

ABU DHABI, UAE — The long-standing debate as to when to start anticoagulation in patients with an acute ischemic stroke and atrial fibrillation (AF) looks as though it’s settled.

Results of the OPTIMAS trial, the largest trial to address this question, showed that initiation of a direct oral anticoagulant (DOAC) within 4 days after ischemic stroke associated with AF was noninferior to delayed initiation (7-14 days) for the composite outcome of ischemic stroke, intracranial hemorrhage, unclassifiable stroke, or systemic embolism at 90 days. Importantly, early DOAC initiation was safe with a low rate of symptomatic hemorrhage, regardless of stroke severity.

In addition, a new meta-analysis, known as CATALYST, which included all four randomized trials now available on this issue, showed a clear benefit of earlier initiation (within 4 days) versus later (5 days and up) on its primary endpoint of new ischemic stroke, symptomatic intracerebral hemorrhage, and unclassified stroke at 30 days.

The results of the OPTIMAS trial and the meta-analysis were both presented at the 16th World Stroke Congress (WSC) 2024. The OPTIMAS trial was also simultaneously published online in The Lancet.

“Our findings do not support the guideline recommended practice of delaying DOAC initiation after ischemic stroke with AF regardless of clinical stroke severity, reperfusion or prior anticoagulation,” said OPTIMAS investigator David Werring, PhD, University College London in England.

Presenting the meta-analysis, Signild Åsberg, MD, Uppsala University, Uppsala, Sweden, said his group’s findings “support the early start of DOACs (within 4 days) in clinical practice.”

Werring pointed out that starting anticoagulation early also had important logistical advantages.

“This means we can start anticoagulation before patients are discharged from hospital, thus ensuring that this important secondary prevention medication is always prescribed, when appropriate. That’s going to be a key benefit in the real world.”
 

Clinical Dilemma

Werring noted that AF accounts for 20%-30% of ischemic strokes, which tend to be more severe than other stroke types. The pivotal trials of DOACs did not include patients within 30 days of an acute ischemic stroke, creating a clinical dilemma on when to start this treatment.

“On the one hand, we wish to start anticoagulation early to reduce early recurrence of ischemic stroke. But on the other hand, there are concerns that if we start anticoagulation early, it could cause intracranial bleeding, including hemorrhagic transformation of the acute infarct. Guidelines on this issue are inconsistent and have called for randomized control trials in this area,” he noted.

So far, three randomized trials on DOAC timing have been conducted, which Werring said suggested early DOAC treatment is safe. However, these trials have provided limited data on moderate to severe stroke, patients with hemorrhagic transformation, or those already taking oral anticoagulants — subgroups in which there are particular concerns about early oral anticoagulation.

The OPTIMAS trial included a broad population of patients with acute ischemic stroke associated with AF including these critical subgroups.

The trial, conducted at 100 hospitals in the United Kingdom, included 3648 patients with AF and acute ischemic stroke who were randomly assigned to early (≤ 4 days from stroke symptom onset) or delayed (7-14 days) anticoagulation initiation with any DOAC.

There was no restriction on stroke severity, and patients with hemorrhagic transformation were allowed, with the exception of parenchymal hematoma type 2, a rare and severe type of hemorrhagic transformation.

Approximately 35% of patients had been taking an oral anticoagulant, mainly DOACs, prior to their stroke, and about 30% had revascularization with thrombolysis, thrombectomy, or both. Nearly 900 participants (25%) had moderate to severe stroke (National Institutes of Health Stroke Scale [NIHSS] score ≥ 11).

The primary outcome was a composite of recurrent ischemic stroke, symptomatic intracranial hemorrhage, unclassifiable stroke, or systemic embolism incidence at 90 days. The initial analysis aimed to show noninferiority of early DOAC initiation, with a noninferiority margin of 2 percentage points, followed by testing for superiority.

Results showed that the primary outcome occurred in 3.3% of both groups (adjusted risk difference, 0.000; 95% CI, −0.011 to 0.012), with noninferiority criteria fulfilled. Superiority was not achieved.

Symptomatic intracranial hemorrhage occurred in 0.6% of patients in the early DOAC initiation group vs 0.7% of those in the delayed group — a nonsignificant difference.
 

Applicable to Real-World Practice

A time-to-event analysis of the primary outcome showed that there were fewer outcomes in the first 30 days in the early DOAC initiation group, but the curves subsequently came together.

Subgroup analysis showed consistent results across all whole trial population, with no modification of the effect of early DOAC initiation according to stroke severity, reperfusion treatment, or previous anticoagulation.

Werring said that strengths of the OPTIMAS trial included a large sample size, a broad population with generalizability to real-world practice, and the inclusion of patients at higher bleeding risk than included in previous studies.

During the discussion, it was noted that the trial included few (about 3%) patients — about 3% — with very severe stroke (NIHSS score > 21), with the question of whether the findings could be applied to this group.

Werring noted that there was no evidence of heterogeneity, and if anything, patients with more severe strokes may have had a slightly greater benefit with early DOAC initiation. “So my feeling is probably these results do generalize to the more severe patients,” he said.

In a commentary accompanying The Lancet publication of the OPTIMAS trial, Else Charlotte Sandset, MD, University of Oslo, in Norway, and Diana Aguiar de Sousa, MD, Central Lisbon University Hospital Centre, Lisbon, Portugal, noted that the “increasing body of evidence strongly supports the message that initiating anticoagulation early for patients with ischaemic stroke is safe. The consistent absence of heterogeneity in safety outcomes suggests that the risk of symptomatic intracranial haemorrhage is not a major concern, even in patients with large infarcts.”

Regardless of the size of the treatment effect, initiating early anticoagulation makes sense when it can be done safely, as it helps prevent recurrent ischemic strokes and other embolic events. Early intervention reduces embolization risk, particularly in high-risk patients, and allows secondary prevention measures to begin while patients are still hospitalized, they added.
 

CATALYST Findings

The CATALYST meta-analysis included four trials, namely, TIMING, ELAN, OPTIMAS, and START, of early versus later DOAC administration in a total of 5411 patients with acute ischemic stroke and AF. In this meta-analysis, early was defined as within 4 days of stroke and later as 5 days or more.

The primary outcome was a composite of ischemic stroke, symptomatic, intracerebral hemorrhage, or unclassified stroke at 30 days. This was significantly reduced in the early group (2.12%) versus 3.02% in the later group, giving an odds ratio of 0.70 (95% CI, 0.50-0.98; P =.04).

The results were consistent across all subgroups, all suggesting an advantage for early DOAC.

Further analysis showed a clear benefit of early DOAC initiation in ischemic stroke with the curves separating early.

The rate of symptomatic intracerebral hemorrhage was low in both groups (0.45% in the early group and 0.40% in the later group) as was extracranial hemorrhage (0.45% vs 0.55%).

At 90 days, there were still lower event rates in the early group than the later one, but the difference was no longer statistically significant.
 

‘Practice Changing’ Results

Commenting on both studies, chair of the WSC session where the results of both OPTIMAS trial and the meta-analysis were presented, Craig Anderson, MD, The George Institute for Global Health, Sydney, Australia, described these latest results as “practice changing.”

“When to start anticoagulation in acute ischemic stroke patients with AF has been uncertain for a long time. The dogma has always been that we should wait. Over the years, we’ve become a little bit more confident, but now we’ve got good data from randomized trials showing that early initiation is safe, with the meta-analysis showing benefit,” he said.

“These new data from OPTIMAS will reassure clinicians that there’s no excessive harm and, more importantly, no excessive harm across all patient groups. And the meta-analysis clearly showed an upfront benefit of starting anticoagulation early. That’s a very convincing result,” he added.

Anderson cautioned that there still may be concerns about starting DOACs early in some groups, including Asian populations that have a higher bleeding risk (these trials included predominantly White patients) and people who are older or frail, who may have extensive small vessel disease.

During the discussion, several questions centered on the lack of imaging data available on the patients in the studies. Anderson said imaging data would help reassure clinicians on the safety of early anticoagulation in patients with large infarcts.

“Stroke clinicians make decisions on the basis of the patient and on the basis of the brain, and we only have the patient information at the moment. We don’t have information on the brain — that comes from imaging.”

Regardless, he believes these new data will lead to a shift in practice. “But maybe, it won’t be as dramatic as we would hope because I think some clinicians may still hesitate to apply these results to patients at high risk of bleeding. With imaging data from the studies that might change.”

The OPTIMAS trial was funded by University College London and the British Heart Foundation. Werring reported consulting fees from Novo Nordisk, National Institute for Health and Care Excellence, and Alnylam; payments or speaker honoraria from Novo Nordisk, Bayer, and AstraZeneca/Alexion; participation on a data safety monitoring board for the OXHARP trial; and participation as steering committee chair for the MACE-ICH and PLINTH trials. Åsberg received institutional research grants and lecture fees to her institution from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and Institut Produits Synthése. Sandset and de Sousa were both steering committee members of the ELAN trial. Anderson reported grant funding from Penumbra and Takeda China.
 

A version of this article appeared on Medscape.com.