Neurology

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.

METHODOLOGY:

• Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
• Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
• The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
• Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.

TAKEAWAY:

• Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
• Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
• The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
• The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.

IN PRACTICE:

“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.

SOURCE:

Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.

LIMITATIONS:

Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.

DISCLOSURES:

This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

PHOENIX — Adding either argatroban or eptifibatide to thrombolytic therapy doesn’t improve function following an ischemic stroke, results of new research show. 

“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri. 

The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said. 

The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.” 

Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective. 

Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto. 

The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.

All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).

Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
 

Two Different Mechanisms

The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.

Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.

The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.

The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial. 

Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study. 

The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.

The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial. 

In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto. 
 

No Increased ICH Risk

The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.

The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug. 

Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase. 

Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.” 

But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence. 

“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.” 
 

Down the Rabbit Hole

Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful. 

“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.” 

He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.” 

Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

PHOENIX — Adding either argatroban or eptifibatide to thrombolytic therapy doesn’t improve function following an ischemic stroke, results of new research show. 

“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri. 

The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said. 

The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.” 

Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective. 

Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto. 

The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.

All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).

Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
 

Two Different Mechanisms

The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.

Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.

The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.

The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial. 

Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study. 

The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.

The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial. 

In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto. 
 

No Increased ICH Risk

The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.

The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug. 

Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase. 

Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.” 

But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence. 

“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.” 
 

Down the Rabbit Hole

Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful. 

“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.” 

He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.” 

Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

PHOENIX — Adding either argatroban or eptifibatide to thrombolytic therapy doesn’t improve function following an ischemic stroke, results of new research show. 

“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri. 

The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said. 

The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.” 

Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective. 

Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto. 

The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.

All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).

Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
 

Two Different Mechanisms

The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.

Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.

The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.

The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial. 

Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study. 

The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.

The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial. 

In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto. 
 

No Increased ICH Risk

The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.

The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug. 

Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase. 

Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.” 

But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence. 

“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.” 
 

Down the Rabbit Hole

Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful. 

“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.” 

He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.” 

Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Habitual consumption of caffeine is not associated with frequency, duration, or intensity of episodic migraines, a new study showed. Investigators said the findings suggest caffeine restrictions in migraineurs may not be necessary.

METHODOLOGY:

• The secondary analysis of a prospective cohort study on sleep in adults with episodic migraine (with or without aura) included a group of 97 people (median age, 31 years; 82% White) with an average of 5.0 ± 3.6  days per month at baseline.
• Participants provided sociodemographic information, medical history, habitual caffeinated beverage consumption, alcohol intake, and lifestyle and psychosocial factors and completed the Center for Epidemiologic Studies- scale, the Perceived Stress Scale, and the Pittsburgh Sleep Quality Index.
• Additionally, they completed twice-daily electronic diaries for the subsequent 6 weeks, reporting headache activity and the use of medications to treat the headache.

TAKEAWAY:

• A total of 67% of participants reported one to two servings of caffeinated beverages per day, 12% reported three to four servings per day, and 21% reported no habitual caffeine consumption.
• After adjusting for age, sex, oral  use, and other confounders, mean headache frequency was similar among groups (7.1 days for no caffeine, 7.4 days for one to two servings, and 5.9 days for three to four servings).
• Similarly, adjusted mean headache duration did not differ across levels of caffeinated beverage intake (8.6 hours for no caffeine, 8.5 hours for one to two servings, and 8.8 hours for three to four servings).
• Adjusted mean headache intensity also did not differ among groups.

IN PRACTICE:

“Our findings do not support a recommendation for people with episodic migraine to avoid habitual caffeinated beverage intake,” the authors wrote. However, they noted that habitual caffeine intake may affect systems involved in pain modulation via adenosine signaling. «Therefore, it is possible that habitual caffeine use in those with migraine does not significantly alter adenosine signaling, but significant changes above or below usual consumption may serve as a trigger or contribute to lowering the threshold for an attack to occur along with other triggers,» they added.

SOURCE:

Suzanne M. Bertisch, MD, MPH, assistant professor of medicine, Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts, was the senior and corresponding author of the study. It was published online in Headache.

LIMITATIONS:

Serving size was not standardized, and there was no information on the type of caffeinated beverage consumed or about other sources of caffeine. Moreover, the population consisted of relatively healthy participants with episodic migraine and generally low levels of habitual caffeinated beverage intake, which limited the statistical power to detect an association between migraine frequency, duration, and intensity with higher levels of caffeine intake.

DISCLOSURES:

The study was funded by the National Institute of Neurological Disorders and Stroke, the American Sleep Medicine Foundation, and the Harvard Catalyst/Harvard Clinical and Translational Science Center. Dr. Bertisch has done consulting work with Idorsia and ResMed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

The Centers for Disease Control and Prevention (CDC) estimates that 1.1% of US adults have epilepsy. Although 89% report seeing a physician in the past year about their condition, only 62% of adults saw a neurologist or seizure specialist. 

These findings prompted Rosemary Kobau, MPH, the acting team lead for the CDC’s epilepsy program, to take a closer look at referral patterns by primary care providers in the United States. Using data from a 2018 online survey of US internists, pediatricians, family medicine physicians, and nurse practitioners, she found that 90% of providers would refer a patient with new-onset seizure to a neurologist.

She also noticed what she calls a “big red flag”: “We found that 40% of primary care providers did not indicate that they would refer their patient with epilepsy to a neurologist when their patient fails to respond to treatment, or if they have a change in seizure activity,” Dr. Kobau told this news organization. Individuals with uncontrolled seizures are at risk for multiple adverse health outcomes, along with emotional problems, social stigma, and decreased life expectancy. 

Factors that influenced primary care clinicians to refer to a neurologist included prompt availability of appointments, ability to talk to the neurologist, and whether a patient’s insurance covered specialty visits. Proximity of a specialist also was cited as a barrier, because neurologists can be hard to find outside of urban centers.

Wait lists for neurologist are not like to get shorter any time soon, according to a 2019 report from the American Academy of Neurology (AAN). A 2013 workforce report from the AAN found 35 US states, representing 62% of the US population, had fewer neurologists than needed to meet demand. By 2025, demand is projected to exceed supply in 41 states. 

Much of the increasing demand for adult neurologists is driven by aging of the population, resulting in higher rates of stroke, Parkinson’s disease, and dementia. But pediatric neurologists are also overwhelmed: Pediatric neurology is one of the top three pediatric subspecialties with the longest wait times. The shortage is exacerbated by difficulties in transitioning adolescents with epilepsy — many diagnosed early in life with neurodevelopmental and epileptic encephalopathy and problem lists that include learning disorders, behavioral issues, and other chronic medical problems — to adult epilepsy specialists. 

Although one of the solutions offered by the AAN is more training in epilepsy management for non-neurologists (such as CME programs developed by the American Epilepsy Society), many primary care providers are overwhelmed already. Still, primary care providers are well-positioned to help answer some of the most important questions about the management of patients with seizure disorders. 
 

How to Help

“There’s a lot the pediatrician can do when a child presents with seizures,” said Sucheta Joshi, MD, who serves as the medical director of the Neurological Institute Comprehensive Epilepsy Center at Children’s Hospital Los Angeles.

Step one is helping to allay the fears of family members who witness a seizure. “They can talk about seizure safety, they can talk about first aid when a seizure happens, they can talk about what to do, what not to do,” she advised. Clinicians who see children can find resources for families on the American Academy of Pediatrics (AAP) National Coordinating Center for Epilepsy website, including a 24/7 helpline, information about local chapters of the Epilepsy Foundation, and first aid training for seizures. 

Fred Lado, MD, PhD, a professor of neurology at the Zucker School of Medicine at Hofstra-Norwell in Hempstead, New York, said that primary care clinicians have several decision points when it comes to their patients with epilepsy.

The first is whether to initiate medication after the first episode of seizure. Studies show that the risk for a second seizure decreases in patients started on anticonvulsant therapy after a first event, but many clinicians don›t want to commit patients to long-term therapy without more evidence that the patient has epilepsy. Studies have shown that delaying therapy until a second seizure occurs doesn›t negatively affect quality of life and long-term prognosis. 

The International League Against Epilepsy (ILAE) advised treatment for patients with two or more unprovoked seizures but revised its recommendation in 2014 to begin treatment after a first seizure for individuals at high risk for a second seizure. History of a brain insult related to a stroke, mass lesion in the brain, or trauma are risk factors for a second seizure, whereas seizures provoked by a concussion, alcohol withdrawal, or exposure to toxins carry low risk for additional episodes.

Dr. Lado also raised the importance of taking a good history from a patient presenting for medical care for a new-onset seizure to determine whether the recent episode is really the first such incident.

Up to half of patients presenting to emergency departments for convulsive seizures have a history of a preceding nonmotor seizure that the patient or their family members have failed to identify. As many as 60% of people with epilepsy have focal seizures, but the majority of these are nonmotor seizures. As a result, these patients often go without a diagnosis until they develop bilateral tonic-clonic seizures — by which time they may already been injured during a seizure or had an accident while driving.

In terms of imaging and other workup that should be performed prior to the first appointment with a pediatric neurologist or epilepsy specialist, Dr. Joshi generally recommends EEG. She also prefers MRI over CT, which is better for finding lesions that tend to cause seizures in kids such as developmental abnormalities like a cortical malformation or a perinatal process. Obtaining an MRI prior to seeing the neurologist is elective, depending on whether the history and clinical presentation suggest a focal lesion.

For adults, Dr. Lado also recommends an EEG and MRI to start but rarely advises other laboratory studies. When patients present to the emergency department with a new-onset seizure, the workup commonly includes a chemistry panel to rule out hypoglycemia or electrolyte abnormalities. But in the outpatient setting, where a patient describes symptoms of a seizure that occurred a week ago or longer, Dr. Lado said the yield of such assessments is low. 

“I think the labs are often more useful as you’re thinking about an anticonvulsant,” Dr. Lado said. Particularly for a patient who is facing a long wait to see specialist, obtaining baseline liver enzymes and a complete blood cell count is worthwhile, because many antiseizure medications can cause anemia or liver damage.

Dr. Lado agreed that referral to a specialist is critical for patients with drug-resistant seizures, defined by the ILAE as seizures that persist despite the use of two or more anticonvulsants. 

“One of the great problems in epilepsy care is a sort of sense of complacency,” he said. Some of his own patients have become comfortable with their epilepsy diagnosis and profess to be untroubled by having a few seizures per year. In 2018, Dr. Kobau was a co-author on a study reporting that less than half of US adults taking seizure medications were seizure-free in the past year. 

This scenario is an opportunity for primary care providers to help determine whether their patients are taking their antiseizure medication correctly. A referral to a specialist might not be necessary if the seizures are occurring because the patient’s prescription ran out. Similarly, if a patient doesn’t take the medication because of unpleasant side effects, raising the dose won’t help. 

Dr. Lado’s advice is to explore why the patient’s management plan is not working and make adjustments tailored to their needs. The solution might be as simple as changing the patient to an extended-release formulation to lower the number of daily doses needed, he said.

But for patients who do have recurrent seizures despite good adherence, Dr. Lado strongly urges a referral to an epilepsy specialist. He serves as president of the National Association of Epilepsy Centers (NAEC), a network of more than 260 epilepsy centers in the United States that offer the services of epileptologists, neurosurgeons, neuropsychologists, nurse specialists, EEG technologists, social workers, and others with training and experience in epilepsy care. In addition to adjusting and monitoring medications, patients seen at an NAEC can be evaluated for surgery, neurostimulators, and ketogenic diets.
 

Improving Self-Management

Another role that primary care can play is promoting self-efficacy among patients with epilepsy.

“Providers have historically tended to focus on medication adherence alone, ignoring other health enhancing behaviors, even just sleep hygiene,” Dr. Kobau said. But adequate sleep, regular exercise, a healthy diet, avoidance of tobacco and excessive alcohol, and stress management are all important for seizure management. 

In 2007, CDC launched the Managing Epilepsy Well (MEW) Network, which has the mission of advancing self-management research in collaboration with patients with epilepsy as well as a broad range of healthcare providers. “It’s a patient-driven kind of approach consistent with community-based, participatory practice research,” said Dr. Kobau, who oversees the initiative.

The MEW network, which consists of six prevention research centers funded by CDC, has piloted and evaluated several evidence-based programs that can help patients better control their epilepsy. 

One such intervention is Project Uplift, which delivers mindfulness-based cognitive-behavioral therapy in a virtual group setting. Behavioral therapy is important for people with seizure disorders, whose risk for depression is more than twice that of the general population. The initial trial found the intervention was effective in reducing depressive symptoms in participants, and research since has focused on adapting the program to provide culturally appropriate care to underserved populations. The eight sessions, held weekly, are available in both English and Spanish.

Another program, HOBSCOTCH, allows patients to meet one-on-one virtually with a trained coach to work on skills for improving attention and memory, common problems among people with epilepsy.

MINDSET involves a tablet-based clinical decision tool that patients can use to track their self-management behaviors, such as taking their medications, seizure triggers, symptoms of depression, and keeping their clinic appointments. It also helps them monitor whether they are getting adequate sleep, reducing their stress, and maintaining social networks. The tool generates a printable action plan for patients to prompt discussion and shared decision-making between patient and clinician to prioritize behavioral issues, set goals, and monitor changes over time.

Clinicians can refer patients to any of the MEW interventions, or patients can enroll themselves online.

 

Emerging Approaches

The AAN’s 2019 report promoted use of technological solutions to bridge the gap between primary care providers and scarce — as well as distant — neurologists. Many health systems support e-consults between clinicians, allowing simple discussions about medications and advice about testing recommended prior to a neurology visit. Initially developed for treatment for infection with hepatitis C virus, Project Extension for Community Healthcare Outcomes (ECHO) uses a central hub of specialists to support primary care providers via teleconference to conduct case reviews and didactic sessions. 

Much of Dr. Joshi’s work has focused on ways to coordinate care to children who live far from a pediatric epilepsy center. In a previous position at the University of Michigan, her team was one of four sites funded by the AAP’s National Coordinating Center for Epilepsy to pilot an intervention using telehealth. Implemented in 2017-2019, the initiative used quality improvement methodology to explore a model where patients went to the office of their primary care provider so that both could participate in the call with a neurologist.

The strategy was successful, resulting in reduced out-of-pocket costs, missed school hours, and missed work hours. Patient satisfaction was high (97%), and more parents in the intervention group than the control group agreed that it was easier to obtain appointments with specialists (95% vs 65%, respectively).

And since the pandemic, in-home telehealth visits have become commonplace, adding to the potential convenience and cost savings of telemedicine. 

CDC has invested in Project ECHO as a training program for nonspecialist providers to manage epilepsy. Based at the University of Cincinnati, the initial pilot from 2017 to 2019 trained primary care providers in Ohio and neighboring states using monthly 1-hour sessions via Zoom. According to Dr. Kobau, “Of those 164 primary care providers, 97% reported higher interest in improving their care of patients with epilepsy, and at least 98% reported that they were more confident in treating their patients with epilepsy.” Since that time, over 900 providers have received the training, which now attracts participants from all over the country.

Although the current burden of managing epilepsy now seems to be falling heavily on primary care providers, Dr. Lado said he believes they can provide useful insight into their patients’ history and needs: “I think they are in a unique and impactful position, mostly to refer those patients who are still having seizures.”
 

Additional Resources for Patients and Providers

• American Academy of Pediatrics National Coordinating Center for Epilepsy 
• American Epilepsy Society  (CME courses designed to designed to increase knowledge about epilepsy diagnosis, treatment, and management; seizure first-aid; epilepsy stigma; and social determinants of health for people with epilepsy)  
• Centers for Disease Control and Prevention   .

Dr. Joshi, Dr. Kobau, and Dr. Lado report no relevant financial relationships. 

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.

A version of this article appeared on Medscape.com .

The Centers for Disease Control and Prevention (CDC) estimates that 1.1% of US adults have epilepsy. Although 89% report seeing a physician in the past year about their condition, only 62% of adults saw a neurologist or seizure specialist. 

These findings prompted Rosemary Kobau, MPH, the acting team lead for the CDC’s epilepsy program, to take a closer look at referral patterns by primary care providers in the United States. Using data from a 2018 online survey of US internists, pediatricians, family medicine physicians, and nurse practitioners, she found that 90% of providers would refer a patient with new-onset seizure to a neurologist.

She also noticed what she calls a “big red flag”: “We found that 40% of primary care providers did not indicate that they would refer their patient with epilepsy to a neurologist when their patient fails to respond to treatment, or if they have a change in seizure activity,” Dr. Kobau told this news organization. Individuals with uncontrolled seizures are at risk for multiple adverse health outcomes, along with emotional problems, social stigma, and decreased life expectancy. 

Factors that influenced primary care clinicians to refer to a neurologist included prompt availability of appointments, ability to talk to the neurologist, and whether a patient’s insurance covered specialty visits. Proximity of a specialist also was cited as a barrier, because neurologists can be hard to find outside of urban centers.

Wait lists for neurologist are not like to get shorter any time soon, according to a 2019 report from the American Academy of Neurology (AAN). A 2013 workforce report from the AAN found 35 US states, representing 62% of the US population, had fewer neurologists than needed to meet demand. By 2025, demand is projected to exceed supply in 41 states. 

Much of the increasing demand for adult neurologists is driven by aging of the population, resulting in higher rates of stroke, Parkinson’s disease, and dementia. But pediatric neurologists are also overwhelmed: Pediatric neurology is one of the top three pediatric subspecialties with the longest wait times. The shortage is exacerbated by difficulties in transitioning adolescents with epilepsy — many diagnosed early in life with neurodevelopmental and epileptic encephalopathy and problem lists that include learning disorders, behavioral issues, and other chronic medical problems — to adult epilepsy specialists. 

Although one of the solutions offered by the AAN is more training in epilepsy management for non-neurologists (such as CME programs developed by the American Epilepsy Society), many primary care providers are overwhelmed already. Still, primary care providers are well-positioned to help answer some of the most important questions about the management of patients with seizure disorders. 
 

How to Help

“There’s a lot the pediatrician can do when a child presents with seizures,” said Sucheta Joshi, MD, who serves as the medical director of the Neurological Institute Comprehensive Epilepsy Center at Children’s Hospital Los Angeles.

Step one is helping to allay the fears of family members who witness a seizure. “They can talk about seizure safety, they can talk about first aid when a seizure happens, they can talk about what to do, what not to do,” she advised. Clinicians who see children can find resources for families on the American Academy of Pediatrics (AAP) National Coordinating Center for Epilepsy website, including a 24/7 helpline, information about local chapters of the Epilepsy Foundation, and first aid training for seizures. 

Fred Lado, MD, PhD, a professor of neurology at the Zucker School of Medicine at Hofstra-Norwell in Hempstead, New York, said that primary care clinicians have several decision points when it comes to their patients with epilepsy.

The first is whether to initiate medication after the first episode of seizure. Studies show that the risk for a second seizure decreases in patients started on anticonvulsant therapy after a first event, but many clinicians don›t want to commit patients to long-term therapy without more evidence that the patient has epilepsy. Studies have shown that delaying therapy until a second seizure occurs doesn›t negatively affect quality of life and long-term prognosis. 

The International League Against Epilepsy (ILAE) advised treatment for patients with two or more unprovoked seizures but revised its recommendation in 2014 to begin treatment after a first seizure for individuals at high risk for a second seizure. History of a brain insult related to a stroke, mass lesion in the brain, or trauma are risk factors for a second seizure, whereas seizures provoked by a concussion, alcohol withdrawal, or exposure to toxins carry low risk for additional episodes.

Dr. Lado also raised the importance of taking a good history from a patient presenting for medical care for a new-onset seizure to determine whether the recent episode is really the first such incident.

Up to half of patients presenting to emergency departments for convulsive seizures have a history of a preceding nonmotor seizure that the patient or their family members have failed to identify. As many as 60% of people with epilepsy have focal seizures, but the majority of these are nonmotor seizures. As a result, these patients often go without a diagnosis until they develop bilateral tonic-clonic seizures — by which time they may already been injured during a seizure or had an accident while driving.

In terms of imaging and other workup that should be performed prior to the first appointment with a pediatric neurologist or epilepsy specialist, Dr. Joshi generally recommends EEG. She also prefers MRI over CT, which is better for finding lesions that tend to cause seizures in kids such as developmental abnormalities like a cortical malformation or a perinatal process. Obtaining an MRI prior to seeing the neurologist is elective, depending on whether the history and clinical presentation suggest a focal lesion.

For adults, Dr. Lado also recommends an EEG and MRI to start but rarely advises other laboratory studies. When patients present to the emergency department with a new-onset seizure, the workup commonly includes a chemistry panel to rule out hypoglycemia or electrolyte abnormalities. But in the outpatient setting, where a patient describes symptoms of a seizure that occurred a week ago or longer, Dr. Lado said the yield of such assessments is low. 

“I think the labs are often more useful as you’re thinking about an anticonvulsant,” Dr. Lado said. Particularly for a patient who is facing a long wait to see specialist, obtaining baseline liver enzymes and a complete blood cell count is worthwhile, because many antiseizure medications can cause anemia or liver damage.

Dr. Lado agreed that referral to a specialist is critical for patients with drug-resistant seizures, defined by the ILAE as seizures that persist despite the use of two or more anticonvulsants. 

“One of the great problems in epilepsy care is a sort of sense of complacency,” he said. Some of his own patients have become comfortable with their epilepsy diagnosis and profess to be untroubled by having a few seizures per year. In 2018, Dr. Kobau was a co-author on a study reporting that less than half of US adults taking seizure medications were seizure-free in the past year. 

This scenario is an opportunity for primary care providers to help determine whether their patients are taking their antiseizure medication correctly. A referral to a specialist might not be necessary if the seizures are occurring because the patient’s prescription ran out. Similarly, if a patient doesn’t take the medication because of unpleasant side effects, raising the dose won’t help. 

Dr. Lado’s advice is to explore why the patient’s management plan is not working and make adjustments tailored to their needs. The solution might be as simple as changing the patient to an extended-release formulation to lower the number of daily doses needed, he said.

But for patients who do have recurrent seizures despite good adherence, Dr. Lado strongly urges a referral to an epilepsy specialist. He serves as president of the National Association of Epilepsy Centers (NAEC), a network of more than 260 epilepsy centers in the United States that offer the services of epileptologists, neurosurgeons, neuropsychologists, nurse specialists, EEG technologists, social workers, and others with training and experience in epilepsy care. In addition to adjusting and monitoring medications, patients seen at an NAEC can be evaluated for surgery, neurostimulators, and ketogenic diets.
 

Improving Self-Management

Another role that primary care can play is promoting self-efficacy among patients with epilepsy.

“Providers have historically tended to focus on medication adherence alone, ignoring other health enhancing behaviors, even just sleep hygiene,” Dr. Kobau said. But adequate sleep, regular exercise, a healthy diet, avoidance of tobacco and excessive alcohol, and stress management are all important for seizure management. 

In 2007, CDC launched the Managing Epilepsy Well (MEW) Network, which has the mission of advancing self-management research in collaboration with patients with epilepsy as well as a broad range of healthcare providers. “It’s a patient-driven kind of approach consistent with community-based, participatory practice research,” said Dr. Kobau, who oversees the initiative.

The MEW network, which consists of six prevention research centers funded by CDC, has piloted and evaluated several evidence-based programs that can help patients better control their epilepsy. 

One such intervention is Project Uplift, which delivers mindfulness-based cognitive-behavioral therapy in a virtual group setting. Behavioral therapy is important for people with seizure disorders, whose risk for depression is more than twice that of the general population. The initial trial found the intervention was effective in reducing depressive symptoms in participants, and research since has focused on adapting the program to provide culturally appropriate care to underserved populations. The eight sessions, held weekly, are available in both English and Spanish.

Another program, HOBSCOTCH, allows patients to meet one-on-one virtually with a trained coach to work on skills for improving attention and memory, common problems among people with epilepsy.

MINDSET involves a tablet-based clinical decision tool that patients can use to track their self-management behaviors, such as taking their medications, seizure triggers, symptoms of depression, and keeping their clinic appointments. It also helps them monitor whether they are getting adequate sleep, reducing their stress, and maintaining social networks. The tool generates a printable action plan for patients to prompt discussion and shared decision-making between patient and clinician to prioritize behavioral issues, set goals, and monitor changes over time.

Clinicians can refer patients to any of the MEW interventions, or patients can enroll themselves online.

 

Emerging Approaches

The AAN’s 2019 report promoted use of technological solutions to bridge the gap between primary care providers and scarce — as well as distant — neurologists. Many health systems support e-consults between clinicians, allowing simple discussions about medications and advice about testing recommended prior to a neurology visit. Initially developed for treatment for infection with hepatitis C virus, Project Extension for Community Healthcare Outcomes (ECHO) uses a central hub of specialists to support primary care providers via teleconference to conduct case reviews and didactic sessions. 

Much of Dr. Joshi’s work has focused on ways to coordinate care to children who live far from a pediatric epilepsy center. In a previous position at the University of Michigan, her team was one of four sites funded by the AAP’s National Coordinating Center for Epilepsy to pilot an intervention using telehealth. Implemented in 2017-2019, the initiative used quality improvement methodology to explore a model where patients went to the office of their primary care provider so that both could participate in the call with a neurologist.

The strategy was successful, resulting in reduced out-of-pocket costs, missed school hours, and missed work hours. Patient satisfaction was high (97%), and more parents in the intervention group than the control group agreed that it was easier to obtain appointments with specialists (95% vs 65%, respectively).

And since the pandemic, in-home telehealth visits have become commonplace, adding to the potential convenience and cost savings of telemedicine. 

CDC has invested in Project ECHO as a training program for nonspecialist providers to manage epilepsy. Based at the University of Cincinnati, the initial pilot from 2017 to 2019 trained primary care providers in Ohio and neighboring states using monthly 1-hour sessions via Zoom. According to Dr. Kobau, “Of those 164 primary care providers, 97% reported higher interest in improving their care of patients with epilepsy, and at least 98% reported that they were more confident in treating their patients with epilepsy.” Since that time, over 900 providers have received the training, which now attracts participants from all over the country.

Although the current burden of managing epilepsy now seems to be falling heavily on primary care providers, Dr. Lado said he believes they can provide useful insight into their patients’ history and needs: “I think they are in a unique and impactful position, mostly to refer those patients who are still having seizures.”
 

Additional Resources for Patients and Providers

• American Academy of Pediatrics National Coordinating Center for Epilepsy 
• American Epilepsy Society  (CME courses designed to designed to increase knowledge about epilepsy diagnosis, treatment, and management; seizure first-aid; epilepsy stigma; and social determinants of health for people with epilepsy)  
• Centers for Disease Control and Prevention   .

Dr. Joshi, Dr. Kobau, and Dr. Lado report no relevant financial relationships. 

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.

A version of this article appeared on Medscape.com .

The Centers for Disease Control and Prevention (CDC) estimates that 1.1% of US adults have epilepsy. Although 89% report seeing a physician in the past year about their condition, only 62% of adults saw a neurologist or seizure specialist. 

These findings prompted Rosemary Kobau, MPH, the acting team lead for the CDC’s epilepsy program, to take a closer look at referral patterns by primary care providers in the United States. Using data from a 2018 online survey of US internists, pediatricians, family medicine physicians, and nurse practitioners, she found that 90% of providers would refer a patient with new-onset seizure to a neurologist.

She also noticed what she calls a “big red flag”: “We found that 40% of primary care providers did not indicate that they would refer their patient with epilepsy to a neurologist when their patient fails to respond to treatment, or if they have a change in seizure activity,” Dr. Kobau told this news organization. Individuals with uncontrolled seizures are at risk for multiple adverse health outcomes, along with emotional problems, social stigma, and decreased life expectancy. 

Factors that influenced primary care clinicians to refer to a neurologist included prompt availability of appointments, ability to talk to the neurologist, and whether a patient’s insurance covered specialty visits. Proximity of a specialist also was cited as a barrier, because neurologists can be hard to find outside of urban centers.

Wait lists for neurologist are not like to get shorter any time soon, according to a 2019 report from the American Academy of Neurology (AAN). A 2013 workforce report from the AAN found 35 US states, representing 62% of the US population, had fewer neurologists than needed to meet demand. By 2025, demand is projected to exceed supply in 41 states. 

Much of the increasing demand for adult neurologists is driven by aging of the population, resulting in higher rates of stroke, Parkinson’s disease, and dementia. But pediatric neurologists are also overwhelmed: Pediatric neurology is one of the top three pediatric subspecialties with the longest wait times. The shortage is exacerbated by difficulties in transitioning adolescents with epilepsy — many diagnosed early in life with neurodevelopmental and epileptic encephalopathy and problem lists that include learning disorders, behavioral issues, and other chronic medical problems — to adult epilepsy specialists. 

Although one of the solutions offered by the AAN is more training in epilepsy management for non-neurologists (such as CME programs developed by the American Epilepsy Society), many primary care providers are overwhelmed already. Still, primary care providers are well-positioned to help answer some of the most important questions about the management of patients with seizure disorders. 
 

How to Help

“There’s a lot the pediatrician can do when a child presents with seizures,” said Sucheta Joshi, MD, who serves as the medical director of the Neurological Institute Comprehensive Epilepsy Center at Children’s Hospital Los Angeles.

Step one is helping to allay the fears of family members who witness a seizure. “They can talk about seizure safety, they can talk about first aid when a seizure happens, they can talk about what to do, what not to do,” she advised. Clinicians who see children can find resources for families on the American Academy of Pediatrics (AAP) National Coordinating Center for Epilepsy website, including a 24/7 helpline, information about local chapters of the Epilepsy Foundation, and first aid training for seizures. 

Fred Lado, MD, PhD, a professor of neurology at the Zucker School of Medicine at Hofstra-Norwell in Hempstead, New York, said that primary care clinicians have several decision points when it comes to their patients with epilepsy.

The first is whether to initiate medication after the first episode of seizure. Studies show that the risk for a second seizure decreases in patients started on anticonvulsant therapy after a first event, but many clinicians don›t want to commit patients to long-term therapy without more evidence that the patient has epilepsy. Studies have shown that delaying therapy until a second seizure occurs doesn›t negatively affect quality of life and long-term prognosis. 

The International League Against Epilepsy (ILAE) advised treatment for patients with two or more unprovoked seizures but revised its recommendation in 2014 to begin treatment after a first seizure for individuals at high risk for a second seizure. History of a brain insult related to a stroke, mass lesion in the brain, or trauma are risk factors for a second seizure, whereas seizures provoked by a concussion, alcohol withdrawal, or exposure to toxins carry low risk for additional episodes.

Dr. Lado also raised the importance of taking a good history from a patient presenting for medical care for a new-onset seizure to determine whether the recent episode is really the first such incident.

Up to half of patients presenting to emergency departments for convulsive seizures have a history of a preceding nonmotor seizure that the patient or their family members have failed to identify. As many as 60% of people with epilepsy have focal seizures, but the majority of these are nonmotor seizures. As a result, these patients often go without a diagnosis until they develop bilateral tonic-clonic seizures — by which time they may already been injured during a seizure or had an accident while driving.

In terms of imaging and other workup that should be performed prior to the first appointment with a pediatric neurologist or epilepsy specialist, Dr. Joshi generally recommends EEG. She also prefers MRI over CT, which is better for finding lesions that tend to cause seizures in kids such as developmental abnormalities like a cortical malformation or a perinatal process. Obtaining an MRI prior to seeing the neurologist is elective, depending on whether the history and clinical presentation suggest a focal lesion.

For adults, Dr. Lado also recommends an EEG and MRI to start but rarely advises other laboratory studies. When patients present to the emergency department with a new-onset seizure, the workup commonly includes a chemistry panel to rule out hypoglycemia or electrolyte abnormalities. But in the outpatient setting, where a patient describes symptoms of a seizure that occurred a week ago or longer, Dr. Lado said the yield of such assessments is low. 

“I think the labs are often more useful as you’re thinking about an anticonvulsant,” Dr. Lado said. Particularly for a patient who is facing a long wait to see specialist, obtaining baseline liver enzymes and a complete blood cell count is worthwhile, because many antiseizure medications can cause anemia or liver damage.

Dr. Lado agreed that referral to a specialist is critical for patients with drug-resistant seizures, defined by the ILAE as seizures that persist despite the use of two or more anticonvulsants. 

“One of the great problems in epilepsy care is a sort of sense of complacency,” he said. Some of his own patients have become comfortable with their epilepsy diagnosis and profess to be untroubled by having a few seizures per year. In 2018, Dr. Kobau was a co-author on a study reporting that less than half of US adults taking seizure medications were seizure-free in the past year. 

This scenario is an opportunity for primary care providers to help determine whether their patients are taking their antiseizure medication correctly. A referral to a specialist might not be necessary if the seizures are occurring because the patient’s prescription ran out. Similarly, if a patient doesn’t take the medication because of unpleasant side effects, raising the dose won’t help. 

Dr. Lado’s advice is to explore why the patient’s management plan is not working and make adjustments tailored to their needs. The solution might be as simple as changing the patient to an extended-release formulation to lower the number of daily doses needed, he said.

But for patients who do have recurrent seizures despite good adherence, Dr. Lado strongly urges a referral to an epilepsy specialist. He serves as president of the National Association of Epilepsy Centers (NAEC), a network of more than 260 epilepsy centers in the United States that offer the services of epileptologists, neurosurgeons, neuropsychologists, nurse specialists, EEG technologists, social workers, and others with training and experience in epilepsy care. In addition to adjusting and monitoring medications, patients seen at an NAEC can be evaluated for surgery, neurostimulators, and ketogenic diets.
 

Improving Self-Management

Another role that primary care can play is promoting self-efficacy among patients with epilepsy.

“Providers have historically tended to focus on medication adherence alone, ignoring other health enhancing behaviors, even just sleep hygiene,” Dr. Kobau said. But adequate sleep, regular exercise, a healthy diet, avoidance of tobacco and excessive alcohol, and stress management are all important for seizure management. 

In 2007, CDC launched the Managing Epilepsy Well (MEW) Network, which has the mission of advancing self-management research in collaboration with patients with epilepsy as well as a broad range of healthcare providers. “It’s a patient-driven kind of approach consistent with community-based, participatory practice research,” said Dr. Kobau, who oversees the initiative.

The MEW network, which consists of six prevention research centers funded by CDC, has piloted and evaluated several evidence-based programs that can help patients better control their epilepsy. 

One such intervention is Project Uplift, which delivers mindfulness-based cognitive-behavioral therapy in a virtual group setting. Behavioral therapy is important for people with seizure disorders, whose risk for depression is more than twice that of the general population. The initial trial found the intervention was effective in reducing depressive symptoms in participants, and research since has focused on adapting the program to provide culturally appropriate care to underserved populations. The eight sessions, held weekly, are available in both English and Spanish.

Another program, HOBSCOTCH, allows patients to meet one-on-one virtually with a trained coach to work on skills for improving attention and memory, common problems among people with epilepsy.

MINDSET involves a tablet-based clinical decision tool that patients can use to track their self-management behaviors, such as taking their medications, seizure triggers, symptoms of depression, and keeping their clinic appointments. It also helps them monitor whether they are getting adequate sleep, reducing their stress, and maintaining social networks. The tool generates a printable action plan for patients to prompt discussion and shared decision-making between patient and clinician to prioritize behavioral issues, set goals, and monitor changes over time.

Clinicians can refer patients to any of the MEW interventions, or patients can enroll themselves online.

 

Emerging Approaches

The AAN’s 2019 report promoted use of technological solutions to bridge the gap between primary care providers and scarce — as well as distant — neurologists. Many health systems support e-consults between clinicians, allowing simple discussions about medications and advice about testing recommended prior to a neurology visit. Initially developed for treatment for infection with hepatitis C virus, Project Extension for Community Healthcare Outcomes (ECHO) uses a central hub of specialists to support primary care providers via teleconference to conduct case reviews and didactic sessions. 

Much of Dr. Joshi’s work has focused on ways to coordinate care to children who live far from a pediatric epilepsy center. In a previous position at the University of Michigan, her team was one of four sites funded by the AAP’s National Coordinating Center for Epilepsy to pilot an intervention using telehealth. Implemented in 2017-2019, the initiative used quality improvement methodology to explore a model where patients went to the office of their primary care provider so that both could participate in the call with a neurologist.

The strategy was successful, resulting in reduced out-of-pocket costs, missed school hours, and missed work hours. Patient satisfaction was high (97%), and more parents in the intervention group than the control group agreed that it was easier to obtain appointments with specialists (95% vs 65%, respectively).

And since the pandemic, in-home telehealth visits have become commonplace, adding to the potential convenience and cost savings of telemedicine. 

CDC has invested in Project ECHO as a training program for nonspecialist providers to manage epilepsy. Based at the University of Cincinnati, the initial pilot from 2017 to 2019 trained primary care providers in Ohio and neighboring states using monthly 1-hour sessions via Zoom. According to Dr. Kobau, “Of those 164 primary care providers, 97% reported higher interest in improving their care of patients with epilepsy, and at least 98% reported that they were more confident in treating their patients with epilepsy.” Since that time, over 900 providers have received the training, which now attracts participants from all over the country.

Although the current burden of managing epilepsy now seems to be falling heavily on primary care providers, Dr. Lado said he believes they can provide useful insight into their patients’ history and needs: “I think they are in a unique and impactful position, mostly to refer those patients who are still having seizures.”
 

Additional Resources for Patients and Providers

• American Academy of Pediatrics National Coordinating Center for Epilepsy 
• American Epilepsy Society  (CME courses designed to designed to increase knowledge about epilepsy diagnosis, treatment, and management; seizure first-aid; epilepsy stigma; and social determinants of health for people with epilepsy)  
• Centers for Disease Control and Prevention   .

Dr. Joshi, Dr. Kobau, and Dr. Lado report no relevant financial relationships. 

Dr. Thomas is a pediatrician and epidemiologist living in Portland, Oregon.

A version of this article appeared on Medscape.com .

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

TOPLINE:

Spinal cord injury (SCI) is associated with a significantly greater risk for heart disease than that of the general non-SCI population, especially among those with severe disability, new observational data suggest.

METHODOLOGY:

• Researchers analyzed data from Korea’s National Health Insurance Service on 5083 patients with cervical, thoracic, or lumbar SCI (mean age, 58; 75% men) and 1:3 age- and sex-matched non-SCI controls.
• The study endpoint was new-onset myocardial infarction (MI), heart failure (HF), or atrial fibrillation (AF) during a mean follow-up of 4.3 years.
• Covariates included low income, living in an urban or rural area, alcohol consumption, smoking status, physical activity engagement, body mass index, and blood pressure; comorbidities included hypertension, type 2 diabetes, and dyslipidemia.

TAKEAWAY:

• A total of 169 MI events (7.3 per 1000 person-years), 426 HF events (18.8 per 1000 person-years), and 158 AF events (6.8 per 1000 person-years) occurred among SCI survivors.
• After adjustment, SCI survivors had a higher risk for MI (adjusted hazard ratio [aHR], 2.41), HF (aHR, 2.24), and AF (aHR, 1.84) than that of controls.
• Among SCI survivors with a disability, the risks increased with disability severity, and those with severe disability had the highest risks for MI (aHR, 3.74), HF (aHR, 3.96), and AF (aHR, 3.32).
• Cervical and lumbar SCI survivors had an increased risk for heart disease compared with controls regardless of disability, and the risk was slightly higher for those with a disability; for cervical SCI survivors with a disability, aHRs for MI, HF, and AF, respectively, were 2.30, 2.05, and 1.73; for lumbar SCI survivors with a disability, aHRs were 2.79, 2.35, and 2.47.
• Thoracic SCI survivors with disability had a higher risk for MI (aHR, 5.62) and HF (aHR, 3.31) than controls.

IN PRACTICE:

“[T]he recognition and treatment of modifiable cardiovascular risk factors must be reinforced in the SCI population, [and] proper rehabilitation and education should be considered to prevent autonomic dysreflexia or orthostatic hypotension,” the authors wrote.

In an accompanying editorial, Christopher R. West, PhD, and Jacquelyn J. Cragg, PhD, both of the University of British Columbia, Vancouver, Canada, noted that clinical guidelines for cardiovascular and cardiometabolic disease after SCI don’t include approaches to help mitigate the risk for cardiac events such as those reported in the study; therefore, they wrote, the findings “should act as ‘call-to-arms’ to researchers and clinicians to shift gears from tradition and begin studying the clinical efficacy of neuraxial therapies that could help restore autonomic balance [in SCI], such as targeted neuromodulation.”

SOURCE:

The study was led by Jung Eun Yoo, MD, PhD of Seoul National University College of Medicine, Seoul, South Korea, and published online on February 12 in the Journal of the American College of Cardiology.

LIMITATIONS:

The database was not designed for the SCI population, so data are incomplete. The incidence of thoracic SCI was particularly low. Because SCI survivors may have impaired perception of chest pain in ischemic heart disease, those with asymptomatic or silent heart disease may not have been captured during follow-up. All study participants were Korean, so the findings may not be generalizable to other ethnicities.

DISCLOSURES:

This research was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, South Korea. The study authors and the editorialists had no relevant relationships to disclose.

A version of this article appeared on Medscape.com.

Intravenous (IV) administration of the antiplatelet agent tirofiban for 72 hours was associated with a reduction in early neurologic deterioration compared with oral aspirin therapy in patients with acute ischemic stroke, in the randomized TREND trial.

The results were presented at the International Stroke Conference 2024, held on February 7-9 in Phoenix, Arizona.

Lead author Zhao Wenbo, MD, Xuanwu Hospital, Beijing, China, noted that neurologic deterioration, characterized by a sudden onset and quick peak of neurologic deficits, is a common phenomenon in acute ischemic stroke and is strongly associated with poor clinical outcomes.

Ischemic stroke progression is the main cause of neurologic deterioration, especially during the first few days after onset, Dr. Wenbo said. Several clinical studies have found that intensive antiplatelet therapy may prevent early neurologic deterioration and improve functional outcomes, but administering oral antiplatelet agents can be difficult because of dysphagia, he reported.

The TREND trial was conducted to investigate whether IV tirofiban could prevent early neurologic deterioration without increasing the risk for symptomatic intracerebral hemorrhage in acute ischemic stroke.

The study included 426 patients with acute ischemic stroke within 24 hours of symptom onset who had a neurologic deficit attributed to focal cerebral ischemia and a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20 points and who were not treated with thrombolysis or endovascular thrombectomy. Patients with cardioembolic stroke were also excluded.

Patients were a median of 10-12 hours from symptom onset and had a baseline NIHSS score of 5.

They were randomized to IV tirofiban or oral aspirin for 72 hours. All patients were then continued on oral antiplatelet therapy.

The primary efficacy outcome was neurologic deterioration within 72 hours after randomization, defined as an increase in NIHSS score of 4 points or more.

This occurred in nine patients (4.2%) in the tirofiban group vs 28 (13.2%) in the control group (relative risk, 0.32; 95% CI, 0.15-0.66; P = .002).

A consistent benefit of IV tirofiban was seen across all subgroups.

The secondary endpoint of neurologic deterioration within 72 hours after randomization, defined as an increase of NIHSS score of 2 points or more, was also significantly reduced. This occurred in 11.7% of the tirofiban group vs 23.6% of the aspirin group (RR, 0.49; 95% CI, 0.32-0.75; P = .001).

An excellent outcome on the modified Rankin Scale (mRS) disability score (mRS, 0-1) at 90 days was seen in 75% of tirofiban vs 68% of aspirin patients, a nonsignificant difference.

A good outcome (mRS, 0-2) occurred in 89% of tirofiban vs 86% of aspirin patients, again a nonsignificant difference.

There were no symptomatic intracerebral hemorrhages within 72 hours after randomization (the primary safety endpoint) in either group, and the incidence of systemic bleeding also did not differ significantly between the groups.

Dr. Wenbo concluded that further randomized clinical trials are needed to determine the efficacy of tirofiban on functional outcomes.

‘Promising Results’

Commenting on the study for this news organization, conference chair, Tudor Jovin, MD, Cooper Medical School of Rowan University, Camden, New Jersey, and vice-chair, Lauren Sansing, MD, Yale School of Medicine, New Haven, Connecticut, both said they thought the results were promising.

“This study didn’t show any long-term outcome benefit, but this was a smaller study, and the results need to be replicated in a larger study with sufficient power to look at longer-term outcomes,” Sansing noted. “But we don’t have anything better than aspirin at present for these patients, so it’s exciting that there may be something in the pipeline for this group.”

Dr. Jovin pointed out that the TREND trial selected patients on the cause of their stroke, in line with the practice of precision medicine.

“By excluding patients who received thrombolysis or thrombectomy and those who had cardioembolic strokes, we are left with a population who we don’t have many treatment options for,” he said. “These are patients with smaller or moderate strokes who may arrive too late for thrombolysis. It would be great to be able to do something more than just aspirin for these patients.”

Dr. Jovin noted that the study was underpowered to show long-term benefits, but there were some promising trends.

“It stands to reason that if neurologic function does not get worse in the early hours and days after stroke, then the long-term outcomes are likely to be better,” he noted. “But this needs to be confirmed in larger trials.”

Interestingly, another study, the MOST trial, also presented at the ISC-24 meeting, showed no benefit with the IV antithrombotic agents argatroban or eptifibatide on 90-day functional outcomes when added to thrombolysis in acute ischemic stroke.

Dr. Jovin pointed out that the MOST and TREND trials included different populations of patients — the MOST patients received thrombolysis, while the TREND patients did not. And in the MOST trial, about half the patients had a large vessel occlusion and underwent thrombectomy, whereas these patients were excluded in TREND.

Dr. Sansing added that patients in the TREND trial may have had small vessel disease or other atherosclerotic disease, or strokes due to the narrowing of vessels or due to an unknown cause. They were also given 3 days of IV tirofiban, whereas the duration of antithrombotic treatment in MOST was shorter.

The TREND study was funded by the National Key Research and Development Program of China, the National Science Foundation of Beijing Municipality, and the Beijing Municipal Science and Technology Commission.

A version of this article appeared on Medscape.com.

Intravenous (IV) administration of the antiplatelet agent tirofiban for 72 hours was associated with a reduction in early neurologic deterioration compared with oral aspirin therapy in patients with acute ischemic stroke, in the randomized TREND trial.

The results were presented at the International Stroke Conference 2024, held on February 7-9 in Phoenix, Arizona.

Lead author Zhao Wenbo, MD, Xuanwu Hospital, Beijing, China, noted that neurologic deterioration, characterized by a sudden onset and quick peak of neurologic deficits, is a common phenomenon in acute ischemic stroke and is strongly associated with poor clinical outcomes.

Ischemic stroke progression is the main cause of neurologic deterioration, especially during the first few days after onset, Dr. Wenbo said. Several clinical studies have found that intensive antiplatelet therapy may prevent early neurologic deterioration and improve functional outcomes, but administering oral antiplatelet agents can be difficult because of dysphagia, he reported.

The TREND trial was conducted to investigate whether IV tirofiban could prevent early neurologic deterioration without increasing the risk for symptomatic intracerebral hemorrhage in acute ischemic stroke.

The study included 426 patients with acute ischemic stroke within 24 hours of symptom onset who had a neurologic deficit attributed to focal cerebral ischemia and a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20 points and who were not treated with thrombolysis or endovascular thrombectomy. Patients with cardioembolic stroke were also excluded.

Patients were a median of 10-12 hours from symptom onset and had a baseline NIHSS score of 5.

They were randomized to IV tirofiban or oral aspirin for 72 hours. All patients were then continued on oral antiplatelet therapy.

The primary efficacy outcome was neurologic deterioration within 72 hours after randomization, defined as an increase in NIHSS score of 4 points or more.

This occurred in nine patients (4.2%) in the tirofiban group vs 28 (13.2%) in the control group (relative risk, 0.32; 95% CI, 0.15-0.66; P = .002).

A consistent benefit of IV tirofiban was seen across all subgroups.

The secondary endpoint of neurologic deterioration within 72 hours after randomization, defined as an increase of NIHSS score of 2 points or more, was also significantly reduced. This occurred in 11.7% of the tirofiban group vs 23.6% of the aspirin group (RR, 0.49; 95% CI, 0.32-0.75; P = .001).

An excellent outcome on the modified Rankin Scale (mRS) disability score (mRS, 0-1) at 90 days was seen in 75% of tirofiban vs 68% of aspirin patients, a nonsignificant difference.

A good outcome (mRS, 0-2) occurred in 89% of tirofiban vs 86% of aspirin patients, again a nonsignificant difference.

There were no symptomatic intracerebral hemorrhages within 72 hours after randomization (the primary safety endpoint) in either group, and the incidence of systemic bleeding also did not differ significantly between the groups.

Dr. Wenbo concluded that further randomized clinical trials are needed to determine the efficacy of tirofiban on functional outcomes.

‘Promising Results’

Commenting on the study for this news organization, conference chair, Tudor Jovin, MD, Cooper Medical School of Rowan University, Camden, New Jersey, and vice-chair, Lauren Sansing, MD, Yale School of Medicine, New Haven, Connecticut, both said they thought the results were promising.

“This study didn’t show any long-term outcome benefit, but this was a smaller study, and the results need to be replicated in a larger study with sufficient power to look at longer-term outcomes,” Sansing noted. “But we don’t have anything better than aspirin at present for these patients, so it’s exciting that there may be something in the pipeline for this group.”

Dr. Jovin pointed out that the TREND trial selected patients on the cause of their stroke, in line with the practice of precision medicine.

“By excluding patients who received thrombolysis or thrombectomy and those who had cardioembolic strokes, we are left with a population who we don’t have many treatment options for,” he said. “These are patients with smaller or moderate strokes who may arrive too late for thrombolysis. It would be great to be able to do something more than just aspirin for these patients.”

Dr. Jovin noted that the study was underpowered to show long-term benefits, but there were some promising trends.

“It stands to reason that if neurologic function does not get worse in the early hours and days after stroke, then the long-term outcomes are likely to be better,” he noted. “But this needs to be confirmed in larger trials.”

Interestingly, another study, the MOST trial, also presented at the ISC-24 meeting, showed no benefit with the IV antithrombotic agents argatroban or eptifibatide on 90-day functional outcomes when added to thrombolysis in acute ischemic stroke.

Dr. Jovin pointed out that the MOST and TREND trials included different populations of patients — the MOST patients received thrombolysis, while the TREND patients did not. And in the MOST trial, about half the patients had a large vessel occlusion and underwent thrombectomy, whereas these patients were excluded in TREND.

Dr. Sansing added that patients in the TREND trial may have had small vessel disease or other atherosclerotic disease, or strokes due to the narrowing of vessels or due to an unknown cause. They were also given 3 days of IV tirofiban, whereas the duration of antithrombotic treatment in MOST was shorter.

The TREND study was funded by the National Key Research and Development Program of China, the National Science Foundation of Beijing Municipality, and the Beijing Municipal Science and Technology Commission.

A version of this article appeared on Medscape.com.

Intravenous (IV) administration of the antiplatelet agent tirofiban for 72 hours was associated with a reduction in early neurologic deterioration compared with oral aspirin therapy in patients with acute ischemic stroke, in the randomized TREND trial.

The results were presented at the International Stroke Conference 2024, held on February 7-9 in Phoenix, Arizona.

Lead author Zhao Wenbo, MD, Xuanwu Hospital, Beijing, China, noted that neurologic deterioration, characterized by a sudden onset and quick peak of neurologic deficits, is a common phenomenon in acute ischemic stroke and is strongly associated with poor clinical outcomes.

Ischemic stroke progression is the main cause of neurologic deterioration, especially during the first few days after onset, Dr. Wenbo said. Several clinical studies have found that intensive antiplatelet therapy may prevent early neurologic deterioration and improve functional outcomes, but administering oral antiplatelet agents can be difficult because of dysphagia, he reported.

The TREND trial was conducted to investigate whether IV tirofiban could prevent early neurologic deterioration without increasing the risk for symptomatic intracerebral hemorrhage in acute ischemic stroke.

The study included 426 patients with acute ischemic stroke within 24 hours of symptom onset who had a neurologic deficit attributed to focal cerebral ischemia and a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20 points and who were not treated with thrombolysis or endovascular thrombectomy. Patients with cardioembolic stroke were also excluded.

Patients were a median of 10-12 hours from symptom onset and had a baseline NIHSS score of 5.

They were randomized to IV tirofiban or oral aspirin for 72 hours. All patients were then continued on oral antiplatelet therapy.

The primary efficacy outcome was neurologic deterioration within 72 hours after randomization, defined as an increase in NIHSS score of 4 points or more.

This occurred in nine patients (4.2%) in the tirofiban group vs 28 (13.2%) in the control group (relative risk, 0.32; 95% CI, 0.15-0.66; P = .002).

A consistent benefit of IV tirofiban was seen across all subgroups.

The secondary endpoint of neurologic deterioration within 72 hours after randomization, defined as an increase of NIHSS score of 2 points or more, was also significantly reduced. This occurred in 11.7% of the tirofiban group vs 23.6% of the aspirin group (RR, 0.49; 95% CI, 0.32-0.75; P = .001).

An excellent outcome on the modified Rankin Scale (mRS) disability score (mRS, 0-1) at 90 days was seen in 75% of tirofiban vs 68% of aspirin patients, a nonsignificant difference.

A good outcome (mRS, 0-2) occurred in 89% of tirofiban vs 86% of aspirin patients, again a nonsignificant difference.

There were no symptomatic intracerebral hemorrhages within 72 hours after randomization (the primary safety endpoint) in either group, and the incidence of systemic bleeding also did not differ significantly between the groups.

Dr. Wenbo concluded that further randomized clinical trials are needed to determine the efficacy of tirofiban on functional outcomes.

‘Promising Results’

Commenting on the study for this news organization, conference chair, Tudor Jovin, MD, Cooper Medical School of Rowan University, Camden, New Jersey, and vice-chair, Lauren Sansing, MD, Yale School of Medicine, New Haven, Connecticut, both said they thought the results were promising.

“This study didn’t show any long-term outcome benefit, but this was a smaller study, and the results need to be replicated in a larger study with sufficient power to look at longer-term outcomes,” Sansing noted. “But we don’t have anything better than aspirin at present for these patients, so it’s exciting that there may be something in the pipeline for this group.”

Dr. Jovin pointed out that the TREND trial selected patients on the cause of their stroke, in line with the practice of precision medicine.

“By excluding patients who received thrombolysis or thrombectomy and those who had cardioembolic strokes, we are left with a population who we don’t have many treatment options for,” he said. “These are patients with smaller or moderate strokes who may arrive too late for thrombolysis. It would be great to be able to do something more than just aspirin for these patients.”

Dr. Jovin noted that the study was underpowered to show long-term benefits, but there were some promising trends.

“It stands to reason that if neurologic function does not get worse in the early hours and days after stroke, then the long-term outcomes are likely to be better,” he noted. “But this needs to be confirmed in larger trials.”

Interestingly, another study, the MOST trial, also presented at the ISC-24 meeting, showed no benefit with the IV antithrombotic agents argatroban or eptifibatide on 90-day functional outcomes when added to thrombolysis in acute ischemic stroke.

Dr. Jovin pointed out that the MOST and TREND trials included different populations of patients — the MOST patients received thrombolysis, while the TREND patients did not. And in the MOST trial, about half the patients had a large vessel occlusion and underwent thrombectomy, whereas these patients were excluded in TREND.

Dr. Sansing added that patients in the TREND trial may have had small vessel disease or other atherosclerotic disease, or strokes due to the narrowing of vessels or due to an unknown cause. They were also given 3 days of IV tirofiban, whereas the duration of antithrombotic treatment in MOST was shorter.

The TREND study was funded by the National Key Research and Development Program of China, the National Science Foundation of Beijing Municipality, and the Beijing Municipal Science and Technology Commission.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at the New York University Grossman School of Medicine in New York City.

I think we had a breakthrough on a very controversial subject over the past month. Over and over again, debates have been breaking out, cases have been going to court, and fights have been coming to ethics committees about brain death. How do we know what brain death is, how do we diagnose it, and what rights do families have with respect to the diagnosis?

The American Academy of Neurology decided to form a task force, and they just issued guidelines on the definition, tests to use it, and the rights of families. Whether you›re a neurologist, someone involved in actually diagnosing brain death, or you›re dealing with very ill people whose families are trying to direct the kinds of things that you or the nurses can do, these guidelines, I think, are excellent. They did a wonderful job, in my view. They›ve achieved clarity.

First, they tried to handle both adults and children. Children are, if you will, more difficult — and that’s been known — to test for brain death. Their brains are smaller. You get more interference and false signals coming from muscle or nerve activity that might be going on elsewhere in their bodies.

The guidelines say we’re going to try to see whether a person can breathe without support. If it’s an adult, one test over a 24-hour period would be sufficient. If you had them off the ventilator and they can’t breathe and show no signs of being able to do that, that’s a very fundamental test for brain death. For children, you’re going to have to do it twice. The guidelines are saying to be cautious.

Second, they say it’s very important to know the cause of the suspected brain death condition. If someone has a massive head injury, that’s different from a situation in which someone overdoses from drugs or drowns. Those conditions can be a little deceptive. In the case of drowning, sometimes the brain has protective mechanisms to protect circulation to the brain naturally for a little bit of time. I’m talking about minutes, not hours.

You want to be careful to make sure that you know the cause of the massive brain injury or insult that makes someone believe that the patient is brain-dead, whether it’s a stroke, an embolism, a bleed, a gunshot wound, or trauma to the head. Those factors really drive the certainty with which brain death should be pronounced. I think that’s very, very important.

They also said that brain death means the permanent loss of brain function. You may get a few cells still firing or you may be in a situation, because the life support is still there, where the body looks pink and perhaps might appear to still be alive to someone. When you know that the damage to the brain is so severe that there’s nothing that can be done to bring back the support of heart function, breathing, and most likely any ability to sense or feel anything, that is death.

I believe it’s very important, when talking to families, to say there are two ways that we pronounce people dead, and they’re equal: One is to say their heart has stopped, their breathing has stopped, and there’s nothing we can do to resuscitate them, which is cardiac death. The other is to say their brain has permanently ceased to function in any kind of integrated way. That means no heartbeat, no breathing, and no mental sensations. That is death.

In approaching families, it is critical that doctors and nurses don’t say, “Your relative is brain-dead.” That gives the family a sense that maybe they’re only “partially dead” or maybe there’s one key organ that has stopped working but maybe you can bring it back. Death is death. The law recognizes both cardiac death and brain death as death.

When you approach a family, if you believe that death has occurred, you say, “I’m very sorry. With regret, I have to tell you, your loved one is dead.” If they ask how you know, you can say, “We’ve determined it through brain death or through cardiac death.” You don’t give them a sense that people could be kind of dead, sort of dead, or nearly dead. Those states are comas or permanent vegetative states; they’re not the same as death.

What if the family says, “I don’t want you to do any testing. I don’t want to find out whether my relative is dead”? The American Academy of Neurology looked at this carefully and said that any test for death can be done without the permission or consent of the family. They said that because doctors need to know what steps to take to treat someone.

If a person is dead, then treatment is going to stop. It may not stop immediately. There may be issues about organ donation. There may be issues about gathering the family to come to the bedside to say goodbye, because many people think that’s more humane than saying goodbye at the morgue or in another setting.

This is all well and good, but patients cannot protect against bad news when it comes to death. We don’t want to be doing things to the dead that cost money or are futile because of death and using resources that might go to others.

We’ve got much more clarity than we have ever had with respect to the issue of brain death and how it works in any hospital. We have certain tests, including being off the ventilator and some other tests, that the guidelines supply. We know we have to be more careful with children. We want to know the etiology of the cause of the brain trauma, the devastating brain injury, to be sure that this is something that really is permanent cessation of integrated brain function.

We know that if you believe the person has died, you don’t need the consent of the family in order to do a brain-death test. You have to do it because there is no point in continuing treatment in expensive ICU settings and denying resources to others who might want to use those resources. The family can’t hold the medical team hostage.

We do know that when we approach someone with the determination, whatever it is, we should lead by saying that the person has died and then explain how that was determined, whether it be by cardiac death pronouncement — where you tried to resuscitate and the heart’s not beating — or brain-death analysis.

I’m Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thanks for watching.

Dr. Caplan has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for: Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position); serves as a contributing author and adviser for this news organization.

A version of this article appeared on Medscape.com.