Clinical Neurology News

As a treatment for small fiber neuropathy (SFN), lacosamide decreased pain and had a positive effect on sleep quality with minimal adverse events in patients with mutations in the gene SCN9A that encodes the voltage-gated sodium channel Na_v1.7, according to a randomized, placebo-controlled, double-blind, crossover-design study published in Brain.

“This is the first study that investigated the efficacy of lacosamide [Vimpat] in patients with SFN,” wrote lead author Bianca T.A. de Greef, MD, of Maastricht University Medical Center, the Netherlands, and her coauthors. “Compared with placebo, lacosamide appeared to be safe to use and well tolerated in this cohort of patients.”

Lacosamide, which is approved in the United States to treat partial-onset seizures in people aged 4 years and older, has been shown to bind to and inhibit Na_v1.7.

The investigators randomized 25 Dutch patients with Na_v1.7-related SFN into the Lacosamide-Efficacy-’N’-Safety in SFN (LENSS) study to receive lacosamide followed by placebo, or vice versa. The patients were recruited between November 2014 and July 2016; 1 patient dropped out before treatment and another after the first treatment period, leaving 24 patients who received lacosamide and 23 patients who received placebo. They went through a 3-week titration period, an 8-week treatment period, a 2-week tapering period, and a washout period of at least 2 weeks, after which they switched to the other treatment arm and repeated the same schedule.

Through the daily pain intensity numerical rating scale and the daily sleep interference scale (DSIS), among other questionnaires, the investigators sought to determine if lacosamide reduced pain and thereby improved sleep quality. Lacosamide treatment led to a decrease in mean average pain by at least 1 point in 50.0% of patients, compared with 21.7% in the placebo group (odds ratio, 4.45; 95% confidence interval, 1.38-14.36; P = .0213). In addition, 25.0% of the lacosamide group reported at least a 2-point decrease in mean average pain versus 8.7% in the placebo group. There was also a notable difference in pain’s impact on sleep quality between the two, with the lacosamide period seeing a DSIS median value of 5.3, compared with 5.7 for the placebo period.

According to the patients’ global impression of change questionnaire, 33.3% felt better while using lacosamide versus 4.3% who felt better while using placebo (P = .0156). Six serious adverse events occurred during the study, though only two occurred during the lacosamide period. The most common adverse events for patients taking lacosamide included dizziness, headache, and nausea, all of which were comparable with adverse events in patients taking placebo.

Dr. de Greef and her colleagues noted the study’s potential limitations, including a carryover effect that could have confounded direct treatment effects (which they attempted to mitigate via a lengthier washout period) and a small cohort that was limited to very specific patients. However, the authors chose this particular cohort because “our aim was to demonstrate proof of-concept, which can be used for future studies involving larger groups of patients diagnosed with SFN.” They observed that their response rates were slightly lower than expected, but they noted that “lacosamide appears to be as effective as currently available neuropathic pain treatment.”

The study was funded by the Prinses Beatrix Spierfonds. Some of the authors reported receiving grants, personal fees, funding for research, and/or honoraria from foundations, pharmaceutical companies, life sciences companies, and the European Commission.

SOURCE: de Greef BTA et al. Brain. 2019 Jan 14. doi: 10.1093/brain/awy329.

As a treatment for small fiber neuropathy (SFN), lacosamide decreased pain and had a positive effect on sleep quality with minimal adverse events in patients with mutations in the gene SCN9A that encodes the voltage-gated sodium channel Na_v1.7, according to a randomized, placebo-controlled, double-blind, crossover-design study published in Brain.

“This is the first study that investigated the efficacy of lacosamide [Vimpat] in patients with SFN,” wrote lead author Bianca T.A. de Greef, MD, of Maastricht University Medical Center, the Netherlands, and her coauthors. “Compared with placebo, lacosamide appeared to be safe to use and well tolerated in this cohort of patients.”

Lacosamide, which is approved in the United States to treat partial-onset seizures in people aged 4 years and older, has been shown to bind to and inhibit Na_v1.7.

The investigators randomized 25 Dutch patients with Na_v1.7-related SFN into the Lacosamide-Efficacy-’N’-Safety in SFN (LENSS) study to receive lacosamide followed by placebo, or vice versa. The patients were recruited between November 2014 and July 2016; 1 patient dropped out before treatment and another after the first treatment period, leaving 24 patients who received lacosamide and 23 patients who received placebo. They went through a 3-week titration period, an 8-week treatment period, a 2-week tapering period, and a washout period of at least 2 weeks, after which they switched to the other treatment arm and repeated the same schedule.

Through the daily pain intensity numerical rating scale and the daily sleep interference scale (DSIS), among other questionnaires, the investigators sought to determine if lacosamide reduced pain and thereby improved sleep quality. Lacosamide treatment led to a decrease in mean average pain by at least 1 point in 50.0% of patients, compared with 21.7% in the placebo group (odds ratio, 4.45; 95% confidence interval, 1.38-14.36; P = .0213). In addition, 25.0% of the lacosamide group reported at least a 2-point decrease in mean average pain versus 8.7% in the placebo group. There was also a notable difference in pain’s impact on sleep quality between the two, with the lacosamide period seeing a DSIS median value of 5.3, compared with 5.7 for the placebo period.

According to the patients’ global impression of change questionnaire, 33.3% felt better while using lacosamide versus 4.3% who felt better while using placebo (P = .0156). Six serious adverse events occurred during the study, though only two occurred during the lacosamide period. The most common adverse events for patients taking lacosamide included dizziness, headache, and nausea, all of which were comparable with adverse events in patients taking placebo.

Dr. de Greef and her colleagues noted the study’s potential limitations, including a carryover effect that could have confounded direct treatment effects (which they attempted to mitigate via a lengthier washout period) and a small cohort that was limited to very specific patients. However, the authors chose this particular cohort because “our aim was to demonstrate proof of-concept, which can be used for future studies involving larger groups of patients diagnosed with SFN.” They observed that their response rates were slightly lower than expected, but they noted that “lacosamide appears to be as effective as currently available neuropathic pain treatment.”

The study was funded by the Prinses Beatrix Spierfonds. Some of the authors reported receiving grants, personal fees, funding for research, and/or honoraria from foundations, pharmaceutical companies, life sciences companies, and the European Commission.

SOURCE: de Greef BTA et al. Brain. 2019 Jan 14. doi: 10.1093/brain/awy329.

As a treatment for small fiber neuropathy (SFN), lacosamide decreased pain and had a positive effect on sleep quality with minimal adverse events in patients with mutations in the gene SCN9A that encodes the voltage-gated sodium channel Na_v1.7, according to a randomized, placebo-controlled, double-blind, crossover-design study published in Brain.

“This is the first study that investigated the efficacy of lacosamide [Vimpat] in patients with SFN,” wrote lead author Bianca T.A. de Greef, MD, of Maastricht University Medical Center, the Netherlands, and her coauthors. “Compared with placebo, lacosamide appeared to be safe to use and well tolerated in this cohort of patients.”

Lacosamide, which is approved in the United States to treat partial-onset seizures in people aged 4 years and older, has been shown to bind to and inhibit Na_v1.7.

The investigators randomized 25 Dutch patients with Na_v1.7-related SFN into the Lacosamide-Efficacy-’N’-Safety in SFN (LENSS) study to receive lacosamide followed by placebo, or vice versa. The patients were recruited between November 2014 and July 2016; 1 patient dropped out before treatment and another after the first treatment period, leaving 24 patients who received lacosamide and 23 patients who received placebo. They went through a 3-week titration period, an 8-week treatment period, a 2-week tapering period, and a washout period of at least 2 weeks, after which they switched to the other treatment arm and repeated the same schedule.

Through the daily pain intensity numerical rating scale and the daily sleep interference scale (DSIS), among other questionnaires, the investigators sought to determine if lacosamide reduced pain and thereby improved sleep quality. Lacosamide treatment led to a decrease in mean average pain by at least 1 point in 50.0% of patients, compared with 21.7% in the placebo group (odds ratio, 4.45; 95% confidence interval, 1.38-14.36; P = .0213). In addition, 25.0% of the lacosamide group reported at least a 2-point decrease in mean average pain versus 8.7% in the placebo group. There was also a notable difference in pain’s impact on sleep quality between the two, with the lacosamide period seeing a DSIS median value of 5.3, compared with 5.7 for the placebo period.

According to the patients’ global impression of change questionnaire, 33.3% felt better while using lacosamide versus 4.3% who felt better while using placebo (P = .0156). Six serious adverse events occurred during the study, though only two occurred during the lacosamide period. The most common adverse events for patients taking lacosamide included dizziness, headache, and nausea, all of which were comparable with adverse events in patients taking placebo.

Dr. de Greef and her colleagues noted the study’s potential limitations, including a carryover effect that could have confounded direct treatment effects (which they attempted to mitigate via a lengthier washout period) and a small cohort that was limited to very specific patients. However, the authors chose this particular cohort because “our aim was to demonstrate proof of-concept, which can be used for future studies involving larger groups of patients diagnosed with SFN.” They observed that their response rates were slightly lower than expected, but they noted that “lacosamide appears to be as effective as currently available neuropathic pain treatment.”

The study was funded by the Prinses Beatrix Spierfonds. Some of the authors reported receiving grants, personal fees, funding for research, and/or honoraria from foundations, pharmaceutical companies, life sciences companies, and the European Commission.

SOURCE: de Greef BTA et al. Brain. 2019 Jan 14. doi: 10.1093/brain/awy329.

Younger people who are enrolled in Medicaid who commit suicide are disproportionately female, younger, and more likely to die by hanging. The risk for acute myeloid leukemia and myeloma is higher for breast cancer survivors, matched transplant improves stroke risk indicator in sickle cell anemia, and a diet low in free sugars shows some promise for adolescent non-alcoholic fatty liver disease.

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Younger people who are enrolled in Medicaid who commit suicide are disproportionately female, younger, and more likely to die by hanging. The risk for acute myeloid leukemia and myeloma is higher for breast cancer survivors, matched transplant improves stroke risk indicator in sickle cell anemia, and a diet low in free sugars shows some promise for adolescent non-alcoholic fatty liver disease.

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Apple Podcasts

Google Podcasts

Spotify
 

Younger people who are enrolled in Medicaid who commit suicide are disproportionately female, younger, and more likely to die by hanging. The risk for acute myeloid leukemia and myeloma is higher for breast cancer survivors, matched transplant improves stroke risk indicator in sickle cell anemia, and a diet low in free sugars shows some promise for adolescent non-alcoholic fatty liver disease.

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Apple Podcasts

Google Podcasts

Spotify
 

A case of emission and injection

In what might win “Most Bizarre Attempt at Home Medicine” of 2019, a 33-year-old Irish man was hospitalized after injecting himself with his own semen … in his arm … multiple times … to reduce back pain. Whew. Does this count as holistic medicine?

Rocky89/Thinkstock

This at-home remedy did not cure his back pain, shockingly enough. The patient instead developed a subcutaneous abscess after a year and a half of monthly intramuscular and intravenous injections, during which the semen has leaked into the soft tissues. He reported to a Dublin hospital after suffering severe back pain and a swollen arm, and eventually revealed to doctors his miracle cure.

The doctors did some Googling and found studies where rats and rabbits were injected with semen – possibly the research that inspired this trailblazer. Or, possibly, this was just an extreme case of reduce, reuse, and recycle.

In case you’re concerned, the man was given a course of more traditional medicine, and his back pain improved greatly. The patient chose to discharge himself before doctors could drain the “local collection” – perhaps he was proud of his work.
 

Down the rabbit hole

Imagine sitting at your computer when suddenly the icons begin to move off the screen and hover directly in front of your eyes. Your first thought might be that someone spiked your morning coffee with acid – and you’re not far off.

Public domain

This curious occurrence happened to a 54-year-old man who was diagnosed with the rare perceptual disorder Alice in Wonderland syndrome (AIWS). AIWS causes people to develop a misperception of their body or surrounding space, and can be caused by a number of things, including migraine.

In this case, the man’s LSD-like visions were caused by a glioblastoma in the left temporal-occipital region of the brain. Tumors there can interfere with spatial perception, hence the temporary trip down the rabbit hole for this patient. After chemotherapy and radiation, the tumor was defeated, and the patient is back to feeling happier than the Mad Hatter at a tea party.
 

Must have been some party

On Dec. 25 in the Vietnamese province of Quang Tri, a 48-year-old man was taken to a hospital with a case of alcohol poisoning. Specifically, his body contained more than 1,000 times the recommended limit of methanol.

Courtesy Len Rizzi /National Cancer Institute

While the two types of alcohol, ethanol and methanol, are both toxic to the human body to some degree, the liver processes methanol differently and more slowly, making it far more dangerous than ethanol, the key ingredient in commercially available alcoholic beverages. Methanol is found in bootleg liquor and in such products as gasoline, paint, ink, and cleaning products. It can cause blindness, nervous system depression, and death.

However, there is a happy ending to this story. To save their patient’s life, his doctors hit upon an ingenious solution – one that would make Homer Simpson proud.

They administered cans of beer.

When the man was admitted, the doctors immediately gave him 3 cans’ worth, and then transfused an additional 12 at the rate of 1 can per hour. The liver will always prioritize processing ethanol over methanol. By feeding the patient a steady stream of relatively friendly and ethanol-rich beer, the doctors had enough time to perform dialysis and remove the methanol from the man’s system.

So, as Homer himself might declare, here’s to alcohol – truly the cause of, and solution to, all of life’s problems.
 

A mistake of the bloody type

Nurse: Mr. Smeggins, I need to clear up some of the answers on your new-patient information form.

Patient: I filled the whole thing out, didn’t I?

John Foxx/Thinkstock

A case of emission and injection

In what might win “Most Bizarre Attempt at Home Medicine” of 2019, a 33-year-old Irish man was hospitalized after injecting himself with his own semen … in his arm … multiple times … to reduce back pain. Whew. Does this count as holistic medicine?

Rocky89/Thinkstock

This at-home remedy did not cure his back pain, shockingly enough. The patient instead developed a subcutaneous abscess after a year and a half of monthly intramuscular and intravenous injections, during which the semen has leaked into the soft tissues. He reported to a Dublin hospital after suffering severe back pain and a swollen arm, and eventually revealed to doctors his miracle cure.

The doctors did some Googling and found studies where rats and rabbits were injected with semen – possibly the research that inspired this trailblazer. Or, possibly, this was just an extreme case of reduce, reuse, and recycle.

In case you’re concerned, the man was given a course of more traditional medicine, and his back pain improved greatly. The patient chose to discharge himself before doctors could drain the “local collection” – perhaps he was proud of his work.
 

Down the rabbit hole

Imagine sitting at your computer when suddenly the icons begin to move off the screen and hover directly in front of your eyes. Your first thought might be that someone spiked your morning coffee with acid – and you’re not far off.

Public domain

This curious occurrence happened to a 54-year-old man who was diagnosed with the rare perceptual disorder Alice in Wonderland syndrome (AIWS). AIWS causes people to develop a misperception of their body or surrounding space, and can be caused by a number of things, including migraine.

In this case, the man’s LSD-like visions were caused by a glioblastoma in the left temporal-occipital region of the brain. Tumors there can interfere with spatial perception, hence the temporary trip down the rabbit hole for this patient. After chemotherapy and radiation, the tumor was defeated, and the patient is back to feeling happier than the Mad Hatter at a tea party.
 

Must have been some party

On Dec. 25 in the Vietnamese province of Quang Tri, a 48-year-old man was taken to a hospital with a case of alcohol poisoning. Specifically, his body contained more than 1,000 times the recommended limit of methanol.

Courtesy Len Rizzi /National Cancer Institute

While the two types of alcohol, ethanol and methanol, are both toxic to the human body to some degree, the liver processes methanol differently and more slowly, making it far more dangerous than ethanol, the key ingredient in commercially available alcoholic beverages. Methanol is found in bootleg liquor and in such products as gasoline, paint, ink, and cleaning products. It can cause blindness, nervous system depression, and death.

However, there is a happy ending to this story. To save their patient’s life, his doctors hit upon an ingenious solution – one that would make Homer Simpson proud.

They administered cans of beer.

When the man was admitted, the doctors immediately gave him 3 cans’ worth, and then transfused an additional 12 at the rate of 1 can per hour. The liver will always prioritize processing ethanol over methanol. By feeding the patient a steady stream of relatively friendly and ethanol-rich beer, the doctors had enough time to perform dialysis and remove the methanol from the man’s system.

So, as Homer himself might declare, here’s to alcohol – truly the cause of, and solution to, all of life’s problems.
 

A mistake of the bloody type

Nurse: Mr. Smeggins, I need to clear up some of the answers on your new-patient information form.

Patient: I filled the whole thing out, didn’t I?

John Foxx/Thinkstock

A case of emission and injection

In what might win “Most Bizarre Attempt at Home Medicine” of 2019, a 33-year-old Irish man was hospitalized after injecting himself with his own semen … in his arm … multiple times … to reduce back pain. Whew. Does this count as holistic medicine?

Rocky89/Thinkstock

This at-home remedy did not cure his back pain, shockingly enough. The patient instead developed a subcutaneous abscess after a year and a half of monthly intramuscular and intravenous injections, during which the semen has leaked into the soft tissues. He reported to a Dublin hospital after suffering severe back pain and a swollen arm, and eventually revealed to doctors his miracle cure.

The doctors did some Googling and found studies where rats and rabbits were injected with semen – possibly the research that inspired this trailblazer. Or, possibly, this was just an extreme case of reduce, reuse, and recycle.

In case you’re concerned, the man was given a course of more traditional medicine, and his back pain improved greatly. The patient chose to discharge himself before doctors could drain the “local collection” – perhaps he was proud of his work.
 

Down the rabbit hole

Imagine sitting at your computer when suddenly the icons begin to move off the screen and hover directly in front of your eyes. Your first thought might be that someone spiked your morning coffee with acid – and you’re not far off.

Public domain

This curious occurrence happened to a 54-year-old man who was diagnosed with the rare perceptual disorder Alice in Wonderland syndrome (AIWS). AIWS causes people to develop a misperception of their body or surrounding space, and can be caused by a number of things, including migraine.

In this case, the man’s LSD-like visions were caused by a glioblastoma in the left temporal-occipital region of the brain. Tumors there can interfere with spatial perception, hence the temporary trip down the rabbit hole for this patient. After chemotherapy and radiation, the tumor was defeated, and the patient is back to feeling happier than the Mad Hatter at a tea party.
 

Must have been some party

On Dec. 25 in the Vietnamese province of Quang Tri, a 48-year-old man was taken to a hospital with a case of alcohol poisoning. Specifically, his body contained more than 1,000 times the recommended limit of methanol.

Courtesy Len Rizzi /National Cancer Institute

While the two types of alcohol, ethanol and methanol, are both toxic to the human body to some degree, the liver processes methanol differently and more slowly, making it far more dangerous than ethanol, the key ingredient in commercially available alcoholic beverages. Methanol is found in bootleg liquor and in such products as gasoline, paint, ink, and cleaning products. It can cause blindness, nervous system depression, and death.

However, there is a happy ending to this story. To save their patient’s life, his doctors hit upon an ingenious solution – one that would make Homer Simpson proud.

They administered cans of beer.

When the man was admitted, the doctors immediately gave him 3 cans’ worth, and then transfused an additional 12 at the rate of 1 can per hour. The liver will always prioritize processing ethanol over methanol. By feeding the patient a steady stream of relatively friendly and ethanol-rich beer, the doctors had enough time to perform dialysis and remove the methanol from the man’s system.

So, as Homer himself might declare, here’s to alcohol – truly the cause of, and solution to, all of life’s problems.
 

A mistake of the bloody type

Nurse: Mr. Smeggins, I need to clear up some of the answers on your new-patient information form.

Patient: I filled the whole thing out, didn’t I?

John Foxx/Thinkstock

Parents were much more confident about vaccinating their children against the human papillomavirus when they were told about the disease that the vaccine prevents rather than about vaccine safety. Also today, FDA labeling templates smooth the way for over-the-counter naloxone, a revised Affordable Care Act premium calculator could increase the rate of uninsured, and confidential parent-free discussion should occur by age 13.

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Apple Podcasts
Google Podcasts
Spotify
 

Parents were much more confident about vaccinating their children against the human papillomavirus when they were told about the disease that the vaccine prevents rather than about vaccine safety. Also today, FDA labeling templates smooth the way for over-the-counter naloxone, a revised Affordable Care Act premium calculator could increase the rate of uninsured, and confidential parent-free discussion should occur by age 13.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Parents were much more confident about vaccinating their children against the human papillomavirus when they were told about the disease that the vaccine prevents rather than about vaccine safety. Also today, FDA labeling templates smooth the way for over-the-counter naloxone, a revised Affordable Care Act premium calculator could increase the rate of uninsured, and confidential parent-free discussion should occur by age 13.

Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

Federal health authorities have proposed new ways to calculate premiums in Affordable Care Act health insurance exchanges and new rules on coverage of abortion services – changes that critics caution could leave more people uninsured.

designer491/Thinkstock

But the Centers for Medicare & Medicaid Services says the changes would lower premiums and give enrollees the option to choose a plan that doesn’t offer abortion services.

The CMS released the proposed rule online Jan. 17, and it’s expected to be published in the Federal Register Jan. 24. (A fact sheet highlighting the changes can be found here.)

Under one of the proposals, the CMS would alter the risk-adjustment model used to determine premium growth beginning in 2020.

But the proposed rule’s regulatory impact statement notes that the risk-adjustment change could reduce enrollment in health insurance products through the federal exchanges by 100,000 people in each of the years from 2020 through 2023. And the revised risk-adjustment model could reduce federal spending on premium tax credits by $900 million in both 2020 and 2021, and by $1 billion in 2022 and 2023.

“Some of the 100,000 individuals estimated to enroll in exchange coverage as a result of the proposed change ... may purchase short-term, limited-duration insurance, though a majority is likely to become uninsured,” the CMS stated in its proposed rule. “Either transition may result in greater exposure to health care costs, which previous research suggests reduces utilization of health care services.”

Matt Fiedler, fellow at the Brookings Institution’s Center for Health Policy, highlighted the potential effect a drop in premium tax credits could have on potential enrollees.

According to Mr. Fiedler, a single person at 300% of the federal poverty level (FPL) would lose $92 per year in premium tax credits. And a family of four at 300% of FPL would lose $189 per year in premium tax credits, he calculated. He predicted “smaller effects at lower income levels and larger effects at higher income levels.”

The proposed rule would also require issuers of qualified health plans that offer abortion services to provide at least one “mirror” plan that omits abortion coverage. That could lead insurers to drop abortion coverage in their qualified health plans, the CMS noted, but it didn’t estimate how many issuers are expected to drop abortion coverage.

The agency said the proposed requirement “would increase consumer choice by offering additional plan options to potential enrollees who may refuse to enroll in, or may be discouraged from enrolling in, qualified health plans because the plans in their service area cover non-Hyde abortion services.” The CMS conceded that the existence of two such plans could confuse consumers, and “research has shown that offering consumers additional health plan options may result in consumers opting to not purchase a plan at all.”

The CMS also is seeking comment on changes to the automatic re-enrollment policy.

“Most current enrollees receive significant government subsidies, making them potentially less sensitive to premiums and premium changes,” the agency stated in the proposed rule. “Some consumers who are automatically re-enrolled in their current plan may be shielded from changes to their coverage, which may result in consumers being less aware of their options from year to year.”

Comments on the proposed rule are due by Feb. 19.

gtwachtman@mdedge.com

Federal health authorities have proposed new ways to calculate premiums in Affordable Care Act health insurance exchanges and new rules on coverage of abortion services – changes that critics caution could leave more people uninsured.

designer491/Thinkstock

But the Centers for Medicare & Medicaid Services says the changes would lower premiums and give enrollees the option to choose a plan that doesn’t offer abortion services.

The CMS released the proposed rule online Jan. 17, and it’s expected to be published in the Federal Register Jan. 24. (A fact sheet highlighting the changes can be found here.)

Under one of the proposals, the CMS would alter the risk-adjustment model used to determine premium growth beginning in 2020.

But the proposed rule’s regulatory impact statement notes that the risk-adjustment change could reduce enrollment in health insurance products through the federal exchanges by 100,000 people in each of the years from 2020 through 2023. And the revised risk-adjustment model could reduce federal spending on premium tax credits by $900 million in both 2020 and 2021, and by $1 billion in 2022 and 2023.

“Some of the 100,000 individuals estimated to enroll in exchange coverage as a result of the proposed change ... may purchase short-term, limited-duration insurance, though a majority is likely to become uninsured,” the CMS stated in its proposed rule. “Either transition may result in greater exposure to health care costs, which previous research suggests reduces utilization of health care services.”

Matt Fiedler, fellow at the Brookings Institution’s Center for Health Policy, highlighted the potential effect a drop in premium tax credits could have on potential enrollees.

According to Mr. Fiedler, a single person at 300% of the federal poverty level (FPL) would lose $92 per year in premium tax credits. And a family of four at 300% of FPL would lose $189 per year in premium tax credits, he calculated. He predicted “smaller effects at lower income levels and larger effects at higher income levels.”

The proposed rule would also require issuers of qualified health plans that offer abortion services to provide at least one “mirror” plan that omits abortion coverage. That could lead insurers to drop abortion coverage in their qualified health plans, the CMS noted, but it didn’t estimate how many issuers are expected to drop abortion coverage.

The agency said the proposed requirement “would increase consumer choice by offering additional plan options to potential enrollees who may refuse to enroll in, or may be discouraged from enrolling in, qualified health plans because the plans in their service area cover non-Hyde abortion services.” The CMS conceded that the existence of two such plans could confuse consumers, and “research has shown that offering consumers additional health plan options may result in consumers opting to not purchase a plan at all.”

The CMS also is seeking comment on changes to the automatic re-enrollment policy.

“Most current enrollees receive significant government subsidies, making them potentially less sensitive to premiums and premium changes,” the agency stated in the proposed rule. “Some consumers who are automatically re-enrolled in their current plan may be shielded from changes to their coverage, which may result in consumers being less aware of their options from year to year.”

Comments on the proposed rule are due by Feb. 19.

gtwachtman@mdedge.com

Federal health authorities have proposed new ways to calculate premiums in Affordable Care Act health insurance exchanges and new rules on coverage of abortion services – changes that critics caution could leave more people uninsured.

designer491/Thinkstock

But the Centers for Medicare & Medicaid Services says the changes would lower premiums and give enrollees the option to choose a plan that doesn’t offer abortion services.

The CMS released the proposed rule online Jan. 17, and it’s expected to be published in the Federal Register Jan. 24. (A fact sheet highlighting the changes can be found here.)

Under one of the proposals, the CMS would alter the risk-adjustment model used to determine premium growth beginning in 2020.

But the proposed rule’s regulatory impact statement notes that the risk-adjustment change could reduce enrollment in health insurance products through the federal exchanges by 100,000 people in each of the years from 2020 through 2023. And the revised risk-adjustment model could reduce federal spending on premium tax credits by $900 million in both 2020 and 2021, and by $1 billion in 2022 and 2023.

“Some of the 100,000 individuals estimated to enroll in exchange coverage as a result of the proposed change ... may purchase short-term, limited-duration insurance, though a majority is likely to become uninsured,” the CMS stated in its proposed rule. “Either transition may result in greater exposure to health care costs, which previous research suggests reduces utilization of health care services.”

Matt Fiedler, fellow at the Brookings Institution’s Center for Health Policy, highlighted the potential effect a drop in premium tax credits could have on potential enrollees.

According to Mr. Fiedler, a single person at 300% of the federal poverty level (FPL) would lose $92 per year in premium tax credits. And a family of four at 300% of FPL would lose $189 per year in premium tax credits, he calculated. He predicted “smaller effects at lower income levels and larger effects at higher income levels.”

The proposed rule would also require issuers of qualified health plans that offer abortion services to provide at least one “mirror” plan that omits abortion coverage. That could lead insurers to drop abortion coverage in their qualified health plans, the CMS noted, but it didn’t estimate how many issuers are expected to drop abortion coverage.

The agency said the proposed requirement “would increase consumer choice by offering additional plan options to potential enrollees who may refuse to enroll in, or may be discouraged from enrolling in, qualified health plans because the plans in their service area cover non-Hyde abortion services.” The CMS conceded that the existence of two such plans could confuse consumers, and “research has shown that offering consumers additional health plan options may result in consumers opting to not purchase a plan at all.”

The CMS also is seeking comment on changes to the automatic re-enrollment policy.

“Most current enrollees receive significant government subsidies, making them potentially less sensitive to premiums and premium changes,” the agency stated in the proposed rule. “Some consumers who are automatically re-enrolled in their current plan may be shielded from changes to their coverage, which may result in consumers being less aware of their options from year to year.”

Comments on the proposed rule are due by Feb. 19.

gtwachtman@mdedge.com

NEW ORLEANS – For people with epilepsy, “the sudden and apparently unpredictable nature of seizures is one of the most disabling aspects of having the disorder,” said Michael Privitera, MD. Reliable seizure forecasts could help patients stay safe, improve their quality of life, and create intervention opportunities to prevent seizures.

If a patient knew that “tomorrow will be a dangerous day” with a 50% chance of having a seizure, the patient could avoid hazardous activities, try to reduce stress, or increase supervision to reduce the risk of sudden, unexpected death in epilepsy, said Dr. Privitera, professor of neurology and director of the epilepsy center at the University of Cincinnati Gardner Neuroscience Institute. Physicians might be able to intervene during high-risk periods by altering antiepileptic drug regimens.

Evidence suggests that seizure prediction is possible today and that advances in wearable devices and analysis of chronic EEG recordings likely will improve the ability to predict seizures, Dr. Privitera said at the annual meeting of the American Epilepsy Society. Studies have found that some patients can predict the likelihood of seizures in the next 24 hours better than chance. In the future, algorithms that incorporate variables such as pulse, stress, mood, electrodermal activity, circadian rhythms, and EEG may further refine seizure prediction.

A complex picture

One problem with predicting seizures is that “you can have substantial changes in the seizure tendency, but not have a seizure,” Dr. Privitera said. Stress, alcohol, and missed medications, for example, may affect the seizure threshold. “They may be additive, and it may be when those things all hit at once that a seizure happens.”

Many patients report prodromal or premonitory symptoms before a seizure. “Most of us as clinicians will say, ‘Well, maybe you have some inkling, but I don’t think you’re really able to predict it,’ ” Dr. Privitera said.

Sheryl R. Haut, MD, professor of neurology at the Albert Einstein College of Medicine, New York, and her colleagues prospectively looked at patient self-prediction in 2007 (Neurology. 2007 Jan 23;68[4]:262-6). The investigators followed 74 people with epilepsy who completed a daily diary in which they predicted the likelihood of a seizure occurring in the next 24 hours. Their analysis included approximately 15,000 diary days and 1,400 seizure days.

A subset of participants, about 20%, was significantly better than chance at predicting when a seizure would happen. If a patient in this subgroup said that a seizure was extremely likely, then a seizure occurred approximately 37% of the time. If a patient predicted that a seizure was extremely unlikely, there was about a 10% chance of having a seizure.

“This was a pretty substantial difference,” Dr. Privitera said. Combining patients’ predictions with their self-reported stress levels seemed to yield the most accurate predictions.
 

Stress and the SMILE study

About 90% of people with epilepsy identify at least one seizure precipitant, and the most commonly cited trigger is stress. When Dr. Privitera and his colleagues surveyed patients in their clinic, 82% identified stress as a trigger (Epilepsy Behav. 2014 Dec;41:74-7). More than half of these patients had used some form of stress reduction, such as exercise, yoga, or meditation; 88% of those patients thought that stress reduction helped their seizures.

Underlying anxiety was the only difference between patients who thought that their seizures were triggered by stress and those who did not. Patients who did not think that stress triggered their seizures had significantly lower scores on the Generalized Anxiety Disorders–7.

Subsequently, Dr. Haut, Dr. Privitera, and colleagues conducted the Stress Management Intervention for Living with Epilepsy (SMILE) study, a prospective, controlled trial assessing the efficacy of a stress reduction intervention for reducing seizures, as well as measuring seizure self-prediction (Neurology. 2018 Mar 13;90[11]:e963-70). The researchers randomized patients to a progressive muscle relaxation intervention or to a control group; patients in the control group wrote down their activities for the day.

Patients posted diary entries twice daily into a smartphone, reporting stress levels and mood-related variables. As in Dr. Haut’s earlier study, patients predicted whether having a seizure was extremely unlikely, unlikely, neutral, likely, or extremely likely. Mood and stress variables (such as feeling unpleasant or pleasant, relaxed or stressed, and not worried or extremely worried) were ranked on a visual analog scale from 0 to 100.

The trial included participants who had at least two seizures per month and any seizure trigger. Medications were kept stable throughout the study. During a 2-month baseline, patients tracked their seizures and stress levels. During the 3-month treatment period, patients received the active or control intervention.

In all, 64 subjects completed the study, completing all diary entries on 94% of the days. In the active-treatment group, median seizure frequency decreased by 29%, compared with a 25% decrease in the control group. However, the difference between the groups was not statistically significant. Although the 25% reduction in the control group probably is partly attributable to the placebo effect, part of the decrease may be related to a mindfulness effect from completing the diary, Dr. Privitera said.

The active-treatment group had a statistically significant reduction in self-reported stress, compared with the control group, but this decrease did not correlate with seizure reduction. Changes in anxiety levels also did not correlate with seizures.

“It does not disprove the [stress] hypothesis, but it does tell us that there is more going on with stress and seizure triggers than just patients’ self-reported stress,” Dr. Privitera said.
 

Patients’ predictions

The seizure prediction findings in SMILE were similar to those of Dr. Haut’s earlier study. Among the 10 highest predictors out of the 64 participants, “when they said that a seizure was extremely likely, they were 8.36 times more likely to have a seizure than when they said a seizure was extremely unlikely,” Dr. Privitera said.

Many patients seemed to increase their predicted seizure probabilities in the days after having a seizure. In addition, feeling sad, nervous, worried, tense, or stressed significantly increased the likelihood that a patient would predict that a seizure was coming. However, these feelings were “not very accurate [for predicting] actual seizures,” he said. “Some people are better predictors, but really the basis of that prediction remains to be seen. One of my hypotheses is that some of these people may actually be responding to subclinical EEG changes.”

Together, these self-prediction studies include data from 4,500 seizures and 26,000 diary entries and show that “there is some information in patient self-report that can help us in understanding how to predict and when to predict seizures,” Dr. Privitera said.

Incorporating cardiac, EEG, and other variables

Various other factors may warrant inclusion in a seizure forecasting system. A new vagus nerve stimulation system responds to heart rate changes that occur at seizure onset. And for decades, researchers have studied the potential for EEG readings to predict seizures. A 2008 analysis of 47 reports concluded that limited progress had been made in predicting a seizure from interictal EEG (Epilepsy Behav. 2008 Jan;12[1]:128-35). Now, however, long-term intracranial recordings are providing new and important information about EEG patterns.

Whereas early studies examined EEG recordings from epilepsy monitoring units – when patients may have been sleep deprived, had medications removed, or recently undergone surgery – chronic intracranial recordings from devices such as the RNS (responsive neurostimulation) System have allowed researchers to look long term at EEG changes that are more representative of patients’ typical EEG patterns.

The RNS System detects interictal spikes and seizure discharges and then provides an electrical stimulation to stop seizures. “When you look at these recordings, there are a lot more electrographic seizures than clinical seizures that trigger these stimulations,” said Dr. Privitera. “If you look at somebody with a typical RNS, they may have 100 stimulations in a day and no clinical seizures. There are lots and lots of subclinical electrographic bursts – and not just spikes, but things that look like short electrographic seizures – that occur throughout the day.”

A handheld device

Researchers in Melbourne designed a system that uses implanted electrodes to provide chronic recordings (Lancet Neurol. 2013 Jun;12[6]:563-71). An algorithm then learned to predict the likelihood of a seizure from the patient’s data as the system recorded over time. The system could indicate when a seizure was likely by displaying a light on a handheld device. Patients were recorded for between 6 months and 3 years.

“There was a statistically significant ability to predict when seizures were happening,” Dr. Privitera said. “There is information in long-term intracranial recordings in many of these people that will help allow us to do a better prediction than what we are able to do right now, which is essentially not much.”

This research suggests that pooling data across patients may not be an effective seizure prediction strategy because different epilepsy types have different patterns. In addition, an individual’s patterns may differ from a group’s patterns. Complicating matters, individual patients may have multiple seizure types with different onset mechanisms.

“Another important lesson is that false positives in a deterministic sense may not represent false positives in a probabilistic sense,” Dr. Privitera said. “That is, when the seizure prediction program – whether it is the diary or the intracranial EEG or anything else – says the threshold changed, but you did not have a seizure, it does not mean that your prediction system was wrong. If the seizure tendency is going up … and your system says the seizure tendency went up, but all you are measuring is actual seizures, it looks like it is a false positive prediction of seizures. But in fact it is a true positive prediction of the seizure tendency changing but not necessarily reaching seizure threshold.”

Multiday patterns

Recent research shows that “we are just at the start,” Dr. Privitera said. “There are patterns underlying seizure frequency that … we are only beginning to be able to look at because of these chronic recordings.”

Baud et al. analyzed interictal epileptiform activity and seizures in patients who have had responsive neurostimulators for as long as 10 years (Nat Commun. 2018 Jan 8;9[1]:88). “What they found was that interictal spikes and rhythmic discharges oscillate with circadian and multiday periods that differ from person to person,” Dr. Privitera said. “There were multiday periodicities, most commonly in the 20- to 30-day duration, that were relatively stable over periods of time that lasted up to years.”

Researchers knew that seizures in women of childbearing age can cluster in association with the menstrual cycle, but similar cycles also were seen in men. In addition, the researchers found that seizures “occur preferentially during the rising phase of these multiday interictal rhythms,” which has implications for seizure forecasts, Dr. Privitera noted.
 

Stress biomarkers and wearables

Future seizure prediction methods may incorporate other biomarkers, such as stress hormones. A researcher at the University of Cincinnati, Jason Heikenfeld, PhD, is conducting research with a sensor that sticks to the wrist and measures sweat content, Dr. Privitera said. The technology originally was developed to measure sodium and potassium in sweat, but Dr. Privitera’s group has been working with him to measure cortisol, which may be a biomarker for stress and be useful for seizure prediction.

“Multivariate models are needed. We have lots of different ways that we can look at seizure prediction, and most likely the most accurate seizure prediction programs will incorporate multiple different areas,” Dr. Privitera said. “Seizure forecasting is possible. We can do it now. We can probably do it better than chance in many patients. ... It is important because changes in seizure likelihood could lead to pharmacologic or device or behavioral interventions that may help prevent seizures.”

Dr. Privitera reported conducting contracted research for Greenwich and SK Life Science and receiving consulting fees from Upsher-Smith and Astellas.

jremaly@mdedge.com

SOURCE: Privitera M. AES 2018, Judith Hoyer Lecture in Epilepsy.

NEW ORLEANS – For people with epilepsy, “the sudden and apparently unpredictable nature of seizures is one of the most disabling aspects of having the disorder,” said Michael Privitera, MD. Reliable seizure forecasts could help patients stay safe, improve their quality of life, and create intervention opportunities to prevent seizures.

If a patient knew that “tomorrow will be a dangerous day” with a 50% chance of having a seizure, the patient could avoid hazardous activities, try to reduce stress, or increase supervision to reduce the risk of sudden, unexpected death in epilepsy, said Dr. Privitera, professor of neurology and director of the epilepsy center at the University of Cincinnati Gardner Neuroscience Institute. Physicians might be able to intervene during high-risk periods by altering antiepileptic drug regimens.

Evidence suggests that seizure prediction is possible today and that advances in wearable devices and analysis of chronic EEG recordings likely will improve the ability to predict seizures, Dr. Privitera said at the annual meeting of the American Epilepsy Society. Studies have found that some patients can predict the likelihood of seizures in the next 24 hours better than chance. In the future, algorithms that incorporate variables such as pulse, stress, mood, electrodermal activity, circadian rhythms, and EEG may further refine seizure prediction.

A complex picture

One problem with predicting seizures is that “you can have substantial changes in the seizure tendency, but not have a seizure,” Dr. Privitera said. Stress, alcohol, and missed medications, for example, may affect the seizure threshold. “They may be additive, and it may be when those things all hit at once that a seizure happens.”

Many patients report prodromal or premonitory symptoms before a seizure. “Most of us as clinicians will say, ‘Well, maybe you have some inkling, but I don’t think you’re really able to predict it,’ ” Dr. Privitera said.

Sheryl R. Haut, MD, professor of neurology at the Albert Einstein College of Medicine, New York, and her colleagues prospectively looked at patient self-prediction in 2007 (Neurology. 2007 Jan 23;68[4]:262-6). The investigators followed 74 people with epilepsy who completed a daily diary in which they predicted the likelihood of a seizure occurring in the next 24 hours. Their analysis included approximately 15,000 diary days and 1,400 seizure days.

A subset of participants, about 20%, was significantly better than chance at predicting when a seizure would happen. If a patient in this subgroup said that a seizure was extremely likely, then a seizure occurred approximately 37% of the time. If a patient predicted that a seizure was extremely unlikely, there was about a 10% chance of having a seizure.

“This was a pretty substantial difference,” Dr. Privitera said. Combining patients’ predictions with their self-reported stress levels seemed to yield the most accurate predictions.
 

Stress and the SMILE study

About 90% of people with epilepsy identify at least one seizure precipitant, and the most commonly cited trigger is stress. When Dr. Privitera and his colleagues surveyed patients in their clinic, 82% identified stress as a trigger (Epilepsy Behav. 2014 Dec;41:74-7). More than half of these patients had used some form of stress reduction, such as exercise, yoga, or meditation; 88% of those patients thought that stress reduction helped their seizures.

Underlying anxiety was the only difference between patients who thought that their seizures were triggered by stress and those who did not. Patients who did not think that stress triggered their seizures had significantly lower scores on the Generalized Anxiety Disorders–7.

Subsequently, Dr. Haut, Dr. Privitera, and colleagues conducted the Stress Management Intervention for Living with Epilepsy (SMILE) study, a prospective, controlled trial assessing the efficacy of a stress reduction intervention for reducing seizures, as well as measuring seizure self-prediction (Neurology. 2018 Mar 13;90[11]:e963-70). The researchers randomized patients to a progressive muscle relaxation intervention or to a control group; patients in the control group wrote down their activities for the day.

Patients posted diary entries twice daily into a smartphone, reporting stress levels and mood-related variables. As in Dr. Haut’s earlier study, patients predicted whether having a seizure was extremely unlikely, unlikely, neutral, likely, or extremely likely. Mood and stress variables (such as feeling unpleasant or pleasant, relaxed or stressed, and not worried or extremely worried) were ranked on a visual analog scale from 0 to 100.

The trial included participants who had at least two seizures per month and any seizure trigger. Medications were kept stable throughout the study. During a 2-month baseline, patients tracked their seizures and stress levels. During the 3-month treatment period, patients received the active or control intervention.

In all, 64 subjects completed the study, completing all diary entries on 94% of the days. In the active-treatment group, median seizure frequency decreased by 29%, compared with a 25% decrease in the control group. However, the difference between the groups was not statistically significant. Although the 25% reduction in the control group probably is partly attributable to the placebo effect, part of the decrease may be related to a mindfulness effect from completing the diary, Dr. Privitera said.

The active-treatment group had a statistically significant reduction in self-reported stress, compared with the control group, but this decrease did not correlate with seizure reduction. Changes in anxiety levels also did not correlate with seizures.

“It does not disprove the [stress] hypothesis, but it does tell us that there is more going on with stress and seizure triggers than just patients’ self-reported stress,” Dr. Privitera said.
 

Patients’ predictions

The seizure prediction findings in SMILE were similar to those of Dr. Haut’s earlier study. Among the 10 highest predictors out of the 64 participants, “when they said that a seizure was extremely likely, they were 8.36 times more likely to have a seizure than when they said a seizure was extremely unlikely,” Dr. Privitera said.

Many patients seemed to increase their predicted seizure probabilities in the days after having a seizure. In addition, feeling sad, nervous, worried, tense, or stressed significantly increased the likelihood that a patient would predict that a seizure was coming. However, these feelings were “not very accurate [for predicting] actual seizures,” he said. “Some people are better predictors, but really the basis of that prediction remains to be seen. One of my hypotheses is that some of these people may actually be responding to subclinical EEG changes.”

Together, these self-prediction studies include data from 4,500 seizures and 26,000 diary entries and show that “there is some information in patient self-report that can help us in understanding how to predict and when to predict seizures,” Dr. Privitera said.

Incorporating cardiac, EEG, and other variables

Various other factors may warrant inclusion in a seizure forecasting system. A new vagus nerve stimulation system responds to heart rate changes that occur at seizure onset. And for decades, researchers have studied the potential for EEG readings to predict seizures. A 2008 analysis of 47 reports concluded that limited progress had been made in predicting a seizure from interictal EEG (Epilepsy Behav. 2008 Jan;12[1]:128-35). Now, however, long-term intracranial recordings are providing new and important information about EEG patterns.

Whereas early studies examined EEG recordings from epilepsy monitoring units – when patients may have been sleep deprived, had medications removed, or recently undergone surgery – chronic intracranial recordings from devices such as the RNS (responsive neurostimulation) System have allowed researchers to look long term at EEG changes that are more representative of patients’ typical EEG patterns.

The RNS System detects interictal spikes and seizure discharges and then provides an electrical stimulation to stop seizures. “When you look at these recordings, there are a lot more electrographic seizures than clinical seizures that trigger these stimulations,” said Dr. Privitera. “If you look at somebody with a typical RNS, they may have 100 stimulations in a day and no clinical seizures. There are lots and lots of subclinical electrographic bursts – and not just spikes, but things that look like short electrographic seizures – that occur throughout the day.”

A handheld device

Researchers in Melbourne designed a system that uses implanted electrodes to provide chronic recordings (Lancet Neurol. 2013 Jun;12[6]:563-71). An algorithm then learned to predict the likelihood of a seizure from the patient’s data as the system recorded over time. The system could indicate when a seizure was likely by displaying a light on a handheld device. Patients were recorded for between 6 months and 3 years.

“There was a statistically significant ability to predict when seizures were happening,” Dr. Privitera said. “There is information in long-term intracranial recordings in many of these people that will help allow us to do a better prediction than what we are able to do right now, which is essentially not much.”

This research suggests that pooling data across patients may not be an effective seizure prediction strategy because different epilepsy types have different patterns. In addition, an individual’s patterns may differ from a group’s patterns. Complicating matters, individual patients may have multiple seizure types with different onset mechanisms.

“Another important lesson is that false positives in a deterministic sense may not represent false positives in a probabilistic sense,” Dr. Privitera said. “That is, when the seizure prediction program – whether it is the diary or the intracranial EEG or anything else – says the threshold changed, but you did not have a seizure, it does not mean that your prediction system was wrong. If the seizure tendency is going up … and your system says the seizure tendency went up, but all you are measuring is actual seizures, it looks like it is a false positive prediction of seizures. But in fact it is a true positive prediction of the seizure tendency changing but not necessarily reaching seizure threshold.”

Multiday patterns

Recent research shows that “we are just at the start,” Dr. Privitera said. “There are patterns underlying seizure frequency that … we are only beginning to be able to look at because of these chronic recordings.”

Baud et al. analyzed interictal epileptiform activity and seizures in patients who have had responsive neurostimulators for as long as 10 years (Nat Commun. 2018 Jan 8;9[1]:88). “What they found was that interictal spikes and rhythmic discharges oscillate with circadian and multiday periods that differ from person to person,” Dr. Privitera said. “There were multiday periodicities, most commonly in the 20- to 30-day duration, that were relatively stable over periods of time that lasted up to years.”

Researchers knew that seizures in women of childbearing age can cluster in association with the menstrual cycle, but similar cycles also were seen in men. In addition, the researchers found that seizures “occur preferentially during the rising phase of these multiday interictal rhythms,” which has implications for seizure forecasts, Dr. Privitera noted.
 

Stress biomarkers and wearables

Future seizure prediction methods may incorporate other biomarkers, such as stress hormones. A researcher at the University of Cincinnati, Jason Heikenfeld, PhD, is conducting research with a sensor that sticks to the wrist and measures sweat content, Dr. Privitera said. The technology originally was developed to measure sodium and potassium in sweat, but Dr. Privitera’s group has been working with him to measure cortisol, which may be a biomarker for stress and be useful for seizure prediction.

“Multivariate models are needed. We have lots of different ways that we can look at seizure prediction, and most likely the most accurate seizure prediction programs will incorporate multiple different areas,” Dr. Privitera said. “Seizure forecasting is possible. We can do it now. We can probably do it better than chance in many patients. ... It is important because changes in seizure likelihood could lead to pharmacologic or device or behavioral interventions that may help prevent seizures.”

Dr. Privitera reported conducting contracted research for Greenwich and SK Life Science and receiving consulting fees from Upsher-Smith and Astellas.

jremaly@mdedge.com

SOURCE: Privitera M. AES 2018, Judith Hoyer Lecture in Epilepsy.

NEW ORLEANS – For people with epilepsy, “the sudden and apparently unpredictable nature of seizures is one of the most disabling aspects of having the disorder,” said Michael Privitera, MD. Reliable seizure forecasts could help patients stay safe, improve their quality of life, and create intervention opportunities to prevent seizures.

If a patient knew that “tomorrow will be a dangerous day” with a 50% chance of having a seizure, the patient could avoid hazardous activities, try to reduce stress, or increase supervision to reduce the risk of sudden, unexpected death in epilepsy, said Dr. Privitera, professor of neurology and director of the epilepsy center at the University of Cincinnati Gardner Neuroscience Institute. Physicians might be able to intervene during high-risk periods by altering antiepileptic drug regimens.

Evidence suggests that seizure prediction is possible today and that advances in wearable devices and analysis of chronic EEG recordings likely will improve the ability to predict seizures, Dr. Privitera said at the annual meeting of the American Epilepsy Society. Studies have found that some patients can predict the likelihood of seizures in the next 24 hours better than chance. In the future, algorithms that incorporate variables such as pulse, stress, mood, electrodermal activity, circadian rhythms, and EEG may further refine seizure prediction.

A complex picture

One problem with predicting seizures is that “you can have substantial changes in the seizure tendency, but not have a seizure,” Dr. Privitera said. Stress, alcohol, and missed medications, for example, may affect the seizure threshold. “They may be additive, and it may be when those things all hit at once that a seizure happens.”

Many patients report prodromal or premonitory symptoms before a seizure. “Most of us as clinicians will say, ‘Well, maybe you have some inkling, but I don’t think you’re really able to predict it,’ ” Dr. Privitera said.

Sheryl R. Haut, MD, professor of neurology at the Albert Einstein College of Medicine, New York, and her colleagues prospectively looked at patient self-prediction in 2007 (Neurology. 2007 Jan 23;68[4]:262-6). The investigators followed 74 people with epilepsy who completed a daily diary in which they predicted the likelihood of a seizure occurring in the next 24 hours. Their analysis included approximately 15,000 diary days and 1,400 seizure days.

A subset of participants, about 20%, was significantly better than chance at predicting when a seizure would happen. If a patient in this subgroup said that a seizure was extremely likely, then a seizure occurred approximately 37% of the time. If a patient predicted that a seizure was extremely unlikely, there was about a 10% chance of having a seizure.

“This was a pretty substantial difference,” Dr. Privitera said. Combining patients’ predictions with their self-reported stress levels seemed to yield the most accurate predictions.
 

Stress and the SMILE study

About 90% of people with epilepsy identify at least one seizure precipitant, and the most commonly cited trigger is stress. When Dr. Privitera and his colleagues surveyed patients in their clinic, 82% identified stress as a trigger (Epilepsy Behav. 2014 Dec;41:74-7). More than half of these patients had used some form of stress reduction, such as exercise, yoga, or meditation; 88% of those patients thought that stress reduction helped their seizures.

Underlying anxiety was the only difference between patients who thought that their seizures were triggered by stress and those who did not. Patients who did not think that stress triggered their seizures had significantly lower scores on the Generalized Anxiety Disorders–7.

Subsequently, Dr. Haut, Dr. Privitera, and colleagues conducted the Stress Management Intervention for Living with Epilepsy (SMILE) study, a prospective, controlled trial assessing the efficacy of a stress reduction intervention for reducing seizures, as well as measuring seizure self-prediction (Neurology. 2018 Mar 13;90[11]:e963-70). The researchers randomized patients to a progressive muscle relaxation intervention or to a control group; patients in the control group wrote down their activities for the day.

Patients posted diary entries twice daily into a smartphone, reporting stress levels and mood-related variables. As in Dr. Haut’s earlier study, patients predicted whether having a seizure was extremely unlikely, unlikely, neutral, likely, or extremely likely. Mood and stress variables (such as feeling unpleasant or pleasant, relaxed or stressed, and not worried or extremely worried) were ranked on a visual analog scale from 0 to 100.

The trial included participants who had at least two seizures per month and any seizure trigger. Medications were kept stable throughout the study. During a 2-month baseline, patients tracked their seizures and stress levels. During the 3-month treatment period, patients received the active or control intervention.

In all, 64 subjects completed the study, completing all diary entries on 94% of the days. In the active-treatment group, median seizure frequency decreased by 29%, compared with a 25% decrease in the control group. However, the difference between the groups was not statistically significant. Although the 25% reduction in the control group probably is partly attributable to the placebo effect, part of the decrease may be related to a mindfulness effect from completing the diary, Dr. Privitera said.

The active-treatment group had a statistically significant reduction in self-reported stress, compared with the control group, but this decrease did not correlate with seizure reduction. Changes in anxiety levels also did not correlate with seizures.

“It does not disprove the [stress] hypothesis, but it does tell us that there is more going on with stress and seizure triggers than just patients’ self-reported stress,” Dr. Privitera said.
 

Patients’ predictions

The seizure prediction findings in SMILE were similar to those of Dr. Haut’s earlier study. Among the 10 highest predictors out of the 64 participants, “when they said that a seizure was extremely likely, they were 8.36 times more likely to have a seizure than when they said a seizure was extremely unlikely,” Dr. Privitera said.

Many patients seemed to increase their predicted seizure probabilities in the days after having a seizure. In addition, feeling sad, nervous, worried, tense, or stressed significantly increased the likelihood that a patient would predict that a seizure was coming. However, these feelings were “not very accurate [for predicting] actual seizures,” he said. “Some people are better predictors, but really the basis of that prediction remains to be seen. One of my hypotheses is that some of these people may actually be responding to subclinical EEG changes.”

Together, these self-prediction studies include data from 4,500 seizures and 26,000 diary entries and show that “there is some information in patient self-report that can help us in understanding how to predict and when to predict seizures,” Dr. Privitera said.

Incorporating cardiac, EEG, and other variables

Various other factors may warrant inclusion in a seizure forecasting system. A new vagus nerve stimulation system responds to heart rate changes that occur at seizure onset. And for decades, researchers have studied the potential for EEG readings to predict seizures. A 2008 analysis of 47 reports concluded that limited progress had been made in predicting a seizure from interictal EEG (Epilepsy Behav. 2008 Jan;12[1]:128-35). Now, however, long-term intracranial recordings are providing new and important information about EEG patterns.

Whereas early studies examined EEG recordings from epilepsy monitoring units – when patients may have been sleep deprived, had medications removed, or recently undergone surgery – chronic intracranial recordings from devices such as the RNS (responsive neurostimulation) System have allowed researchers to look long term at EEG changes that are more representative of patients’ typical EEG patterns.

The RNS System detects interictal spikes and seizure discharges and then provides an electrical stimulation to stop seizures. “When you look at these recordings, there are a lot more electrographic seizures than clinical seizures that trigger these stimulations,” said Dr. Privitera. “If you look at somebody with a typical RNS, they may have 100 stimulations in a day and no clinical seizures. There are lots and lots of subclinical electrographic bursts – and not just spikes, but things that look like short electrographic seizures – that occur throughout the day.”

A handheld device

Researchers in Melbourne designed a system that uses implanted electrodes to provide chronic recordings (Lancet Neurol. 2013 Jun;12[6]:563-71). An algorithm then learned to predict the likelihood of a seizure from the patient’s data as the system recorded over time. The system could indicate when a seizure was likely by displaying a light on a handheld device. Patients were recorded for between 6 months and 3 years.

“There was a statistically significant ability to predict when seizures were happening,” Dr. Privitera said. “There is information in long-term intracranial recordings in many of these people that will help allow us to do a better prediction than what we are able to do right now, which is essentially not much.”

This research suggests that pooling data across patients may not be an effective seizure prediction strategy because different epilepsy types have different patterns. In addition, an individual’s patterns may differ from a group’s patterns. Complicating matters, individual patients may have multiple seizure types with different onset mechanisms.

“Another important lesson is that false positives in a deterministic sense may not represent false positives in a probabilistic sense,” Dr. Privitera said. “That is, when the seizure prediction program – whether it is the diary or the intracranial EEG or anything else – says the threshold changed, but you did not have a seizure, it does not mean that your prediction system was wrong. If the seizure tendency is going up … and your system says the seizure tendency went up, but all you are measuring is actual seizures, it looks like it is a false positive prediction of seizures. But in fact it is a true positive prediction of the seizure tendency changing but not necessarily reaching seizure threshold.”

Multiday patterns

Recent research shows that “we are just at the start,” Dr. Privitera said. “There are patterns underlying seizure frequency that … we are only beginning to be able to look at because of these chronic recordings.”

Baud et al. analyzed interictal epileptiform activity and seizures in patients who have had responsive neurostimulators for as long as 10 years (Nat Commun. 2018 Jan 8;9[1]:88). “What they found was that interictal spikes and rhythmic discharges oscillate with circadian and multiday periods that differ from person to person,” Dr. Privitera said. “There were multiday periodicities, most commonly in the 20- to 30-day duration, that were relatively stable over periods of time that lasted up to years.”

Researchers knew that seizures in women of childbearing age can cluster in association with the menstrual cycle, but similar cycles also were seen in men. In addition, the researchers found that seizures “occur preferentially during the rising phase of these multiday interictal rhythms,” which has implications for seizure forecasts, Dr. Privitera noted.
 

Stress biomarkers and wearables

Future seizure prediction methods may incorporate other biomarkers, such as stress hormones. A researcher at the University of Cincinnati, Jason Heikenfeld, PhD, is conducting research with a sensor that sticks to the wrist and measures sweat content, Dr. Privitera said. The technology originally was developed to measure sodium and potassium in sweat, but Dr. Privitera’s group has been working with him to measure cortisol, which may be a biomarker for stress and be useful for seizure prediction.

“Multivariate models are needed. We have lots of different ways that we can look at seizure prediction, and most likely the most accurate seizure prediction programs will incorporate multiple different areas,” Dr. Privitera said. “Seizure forecasting is possible. We can do it now. We can probably do it better than chance in many patients. ... It is important because changes in seizure likelihood could lead to pharmacologic or device or behavioral interventions that may help prevent seizures.”

Dr. Privitera reported conducting contracted research for Greenwich and SK Life Science and receiving consulting fees from Upsher-Smith and Astellas.

jremaly@mdedge.com

SOURCE: Privitera M. AES 2018, Judith Hoyer Lecture in Epilepsy.

Ezetimibe is found to be effective in lowering LDL for primary cardiovascular prevention in patients who were 75 or older. Also today, the FDA says that the benefits of paclitaxel-coated devices outweigh risks for peripheral arterial disease, flu activity is down for the second consecutive week, and a look at homelessness among LGBT youth in the United States.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Ezetimibe is found to be effective in lowering LDL for primary cardiovascular prevention in patients who were 75 or older. Also today, the FDA says that the benefits of paclitaxel-coated devices outweigh risks for peripheral arterial disease, flu activity is down for the second consecutive week, and a look at homelessness among LGBT youth in the United States.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Ezetimibe is found to be effective in lowering LDL for primary cardiovascular prevention in patients who were 75 or older. Also today, the FDA says that the benefits of paclitaxel-coated devices outweigh risks for peripheral arterial disease, flu activity is down for the second consecutive week, and a look at homelessness among LGBT youth in the United States.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

A majority of U.S. healthcare professionals report that their patients have been negatively affected by the partial shutdown of the federal government. Also today, a mental disorder diagnosis increases the risk for all mental disorders, frailty may affect the expression of dementia, and nearly one-quarter of antibiotic fills are deemed unnecessary.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

A majority of U.S. healthcare professionals report that their patients have been negatively affected by the partial shutdown of the federal government. Also today, a mental disorder diagnosis increases the risk for all mental disorders, frailty may affect the expression of dementia, and nearly one-quarter of antibiotic fills are deemed unnecessary.
Amazon Alexa
Apple Podcasts
Google Podcasts
Spotify
 

A majority of U.S. healthcare professionals report that their patients have been negatively affected by the partial shutdown of the federal government. Also today, a mental disorder diagnosis increases the risk for all mental disorders, frailty may affect the expression of dementia, and nearly one-quarter of antibiotic fills are deemed unnecessary.
Amazon Alexa
Apple Podcasts
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The Food and Drug Administration has smoothed the way to OTC naloxone by releasing “drug facts label” templates for manufacturers to use when submitting their products for consideration.

Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.

“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.

There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.

As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.

Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.

In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”

aotto@mdedge.com

The Food and Drug Administration has smoothed the way to OTC naloxone by releasing “drug facts label” templates for manufacturers to use when submitting their products for consideration.

Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.

“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.

There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.

As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.

Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.

In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”

aotto@mdedge.com

The Food and Drug Administration has smoothed the way to OTC naloxone by releasing “drug facts label” templates for manufacturers to use when submitting their products for consideration.

Drug facts labels (DFLs) are required for all OTC drugs, and it’s usually up to manufacturers to develop and test their own to ensure that consumers understand how to use their products.

“Some stakeholders have identified the requirement ... as a barrier to development of OTC naloxone products,” so the agency developed two DFLs on its own – one for nasal spray naloxone, the other for auto-injectors – and completed the necessary label comprehension testing, according to an announcement from FDA Commissioner Scott Gottlieb, MD.

There’s not much else manufactures have to do, except deal with the details of their own products. They “can now focus their efforts on ... how well consumers understand the product-specific information that hasn’t been already tested in the model” DFLs, according to the announcement.

As deaths from opioid abuse continue to climb, the FDA is committed to increasing access to naloxone, which currently requires a prescription. The new DFLs “should jump-start the development of OTC naloxone products ... I personally urge companies to take notice of this pathway that the FDA has opened for them and come to the Agency with applications as soon as possible,” Dr. Gottlieb said.

Comprehension was assessed in more than 700 people, including heroin and prescription opioid users, their friends and families, and adolescents. “Overall, the study demonstrated that” the DFLs are “well-understood by consumers” and acceptable “for use by manufacturers in support of their ... development programs,” according to the announcement.

In a press statement, the American Medical Association applauded the agency’s move “to provide labeling that would allow for over-the-counter availability of naloxone, a move that will save people from opioid-related overdose ... The action should spur efforts by naloxone manufacturers to submit applications for their products to receive over-the-counter status.”

aotto@mdedge.com

Anti-vaccination protesters targeted Monique A. Tello, MD, MPH, in late summer 2018 by leaving bad online ratings and writing false and defamatory comments in her online profiles. Dr. Tell wrote about her experience in a blog post where she opened up about how difficult the process has been, and how she has found support in a community of her colleagues.
Apple Podcasts
Google Podcasts
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Anti-vaccination protesters targeted Monique A. Tello, MD, MPH, in late summer 2018 by leaving bad online ratings and writing false and defamatory comments in her online profiles. Dr. Tell wrote about her experience in a blog post where she opened up about how difficult the process has been, and how she has found support in a community of her colleagues.
Apple Podcasts
Google Podcasts
Spotify

Anti-vaccination protesters targeted Monique A. Tello, MD, MPH, in late summer 2018 by leaving bad online ratings and writing false and defamatory comments in her online profiles. Dr. Tell wrote about her experience in a blog post where she opened up about how difficult the process has been, and how she has found support in a community of her colleagues.
Apple Podcasts
Google Podcasts
Spotify