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Marijuana calms children with autism
SAN FRANCISCO – About once a month, Antonio Y. Hardan, MD, and his colleagues at the Stanford (Calif.) University Autism and Developmental Disorders Clinic see an autistic child who is using or being prescribed marijuana.
“There are two types or responses we see with marijuana,” said Dr. Hardan, director of the clinic. “Most of the time, it calms the kid down for 2 or 3 hours, which is what you’d expect from marijuana. In one out of 10, I am hearing that parents see improvements in the core features of autism. We have several families who would swear by marijuana, but then 4 or 6 months later, they will change their mind and say it’s not helping as much.
Marijuana is just one of many alternatives families and doctors are trying to improve upon the usual medications and therapies for autism; the range of options being tried speaks to the desperation and frustration of families looking for help. There’s no home run so far; the common denominator for alternatives is anecdotal support but little evidence. Stanford has tried to address the evidence gap and continues to do so.
In 2012, for instance, Dr. Hardan and his colleagues reported a 33 patient study that found that N-acetylcysteine (NAC) – another hopeful candidate in recent years – might curb irritability (Biol Psychiatry. 2012 Jun 1;71[11]:956-61).
The tricky part about NAC is that it’s a dietary supplement, so you can’t be sure of what you’re getting in the store. There were questions at the talk about dose and formulations.
“The one we used in the study is made by BioAdvantex,” a Canadian company. “That’s the one that worked for us. One of the advantages is that every dose is wrapped individually.” NAC is an antioxidant, “so if you expose [it] to oxygen or light, it will get oxidized, and over time be less effective,” said Dr. Hardan, also a professor of psychiatry and behavioral sciences at the university.
Most of the time, NAC is very well tolerated, with only a little bit of flatulence and upset stomach.
Dr. Hardan and his colleagues started with 900 mg in one dose once a day for 4 weeks, then one dose twice a day for 4 weeks, followed by one dose three times daily, in children aged 2-12 years old. With experience, they are going faster now, cutting the 4 week interval to 2. “Some people are [even] more aggressive, which is okay,” he said.
Propranolol is another fashionable option, prescribed by a lot of doctors.
It’s not a new option; about 20 years ago, “we used it in very high dosages, 700-800 mg a day for self-injurious behavior. People wonder how you can go that high; above a dose of 200 mg, there is what we call an ‘escape phenomena’ where the heart will stop responding, and the effects on blood pressure and pulse are minimal,” Dr. Hardan said.
Interest in propranolol over the past 5 years has expanded to anxiety, sensory abnormalities, and other non-specific autism symptoms. “Unfortunately, there are no clinical trials to support that,” he said. The only evidence so far is from a functional MRI study in adults that suggested a little bit more efficient processing on a language task; further investigation is underway.
A lot of parents also are asking for oxytocin, and doctors are prescribing it. Someone in the audience wondered whether it had a role in everyday practice.
“Not at this time,” Dr. Hardan said. “I would suggest waiting a little bit until” results are reported from an ongoing trial. They are due soon, and there might be a subgroup of kids who benefit. Oxytocin seemed to help all-comers recognize facial cues.
Arginine vasopressin might do that, too, and be more specific for autism; Stanford is planning a study to look into it.
Attendees also wanted to know what to do about sleep problems, a common issue in autism.
“I’m aggressive in the treatment of insomnia, especially in single-parent households, because if the kid isn’t sleeping, the parent isn’t sleeping” and they may get irritable and moody, which raises the risk of abuse, Dr. Hardan said.
He starts with melatonin, 1 mg in the evening, and increases it by 1 mg every week to hit a target of 6 mg per night. He hasn’t seen much benefit of going higher. It’s important to remember that melatonin might take up to a week to see the full effect.
If melatonin fails, Dr. Hardan goes up the ladder. Diphenhydramine (Benadryl), benzodiazepines, trazodone (Oleptro), and mirtazapine (Remeron) are among the options. Rarely, there’s a need for quetiapine (Seroquel).
To counter benzodiazepine disinhibition, he asks parents to try them on a good day at home, so the effect of environmental stressors like going to the dentist can be divided out from the drug.
Dr. Hardan cautioned that there is “no evidence at this time to support the use of” lamotrigine (Lamictal). “Please don’t use it; somebody will end up developing” Stevens-Johnson syndrome. “It will be difficult to defend against that.”
Dr. Hardan is an adviser for Roche.
SAN FRANCISCO – About once a month, Antonio Y. Hardan, MD, and his colleagues at the Stanford (Calif.) University Autism and Developmental Disorders Clinic see an autistic child who is using or being prescribed marijuana.
“There are two types or responses we see with marijuana,” said Dr. Hardan, director of the clinic. “Most of the time, it calms the kid down for 2 or 3 hours, which is what you’d expect from marijuana. In one out of 10, I am hearing that parents see improvements in the core features of autism. We have several families who would swear by marijuana, but then 4 or 6 months later, they will change their mind and say it’s not helping as much.
Marijuana is just one of many alternatives families and doctors are trying to improve upon the usual medications and therapies for autism; the range of options being tried speaks to the desperation and frustration of families looking for help. There’s no home run so far; the common denominator for alternatives is anecdotal support but little evidence. Stanford has tried to address the evidence gap and continues to do so.
In 2012, for instance, Dr. Hardan and his colleagues reported a 33 patient study that found that N-acetylcysteine (NAC) – another hopeful candidate in recent years – might curb irritability (Biol Psychiatry. 2012 Jun 1;71[11]:956-61).
The tricky part about NAC is that it’s a dietary supplement, so you can’t be sure of what you’re getting in the store. There were questions at the talk about dose and formulations.
“The one we used in the study is made by BioAdvantex,” a Canadian company. “That’s the one that worked for us. One of the advantages is that every dose is wrapped individually.” NAC is an antioxidant, “so if you expose [it] to oxygen or light, it will get oxidized, and over time be less effective,” said Dr. Hardan, also a professor of psychiatry and behavioral sciences at the university.
Most of the time, NAC is very well tolerated, with only a little bit of flatulence and upset stomach.
Dr. Hardan and his colleagues started with 900 mg in one dose once a day for 4 weeks, then one dose twice a day for 4 weeks, followed by one dose three times daily, in children aged 2-12 years old. With experience, they are going faster now, cutting the 4 week interval to 2. “Some people are [even] more aggressive, which is okay,” he said.
Propranolol is another fashionable option, prescribed by a lot of doctors.
It’s not a new option; about 20 years ago, “we used it in very high dosages, 700-800 mg a day for self-injurious behavior. People wonder how you can go that high; above a dose of 200 mg, there is what we call an ‘escape phenomena’ where the heart will stop responding, and the effects on blood pressure and pulse are minimal,” Dr. Hardan said.
Interest in propranolol over the past 5 years has expanded to anxiety, sensory abnormalities, and other non-specific autism symptoms. “Unfortunately, there are no clinical trials to support that,” he said. The only evidence so far is from a functional MRI study in adults that suggested a little bit more efficient processing on a language task; further investigation is underway.
A lot of parents also are asking for oxytocin, and doctors are prescribing it. Someone in the audience wondered whether it had a role in everyday practice.
“Not at this time,” Dr. Hardan said. “I would suggest waiting a little bit until” results are reported from an ongoing trial. They are due soon, and there might be a subgroup of kids who benefit. Oxytocin seemed to help all-comers recognize facial cues.
Arginine vasopressin might do that, too, and be more specific for autism; Stanford is planning a study to look into it.
Attendees also wanted to know what to do about sleep problems, a common issue in autism.
“I’m aggressive in the treatment of insomnia, especially in single-parent households, because if the kid isn’t sleeping, the parent isn’t sleeping” and they may get irritable and moody, which raises the risk of abuse, Dr. Hardan said.
He starts with melatonin, 1 mg in the evening, and increases it by 1 mg every week to hit a target of 6 mg per night. He hasn’t seen much benefit of going higher. It’s important to remember that melatonin might take up to a week to see the full effect.
If melatonin fails, Dr. Hardan goes up the ladder. Diphenhydramine (Benadryl), benzodiazepines, trazodone (Oleptro), and mirtazapine (Remeron) are among the options. Rarely, there’s a need for quetiapine (Seroquel).
To counter benzodiazepine disinhibition, he asks parents to try them on a good day at home, so the effect of environmental stressors like going to the dentist can be divided out from the drug.
Dr. Hardan cautioned that there is “no evidence at this time to support the use of” lamotrigine (Lamictal). “Please don’t use it; somebody will end up developing” Stevens-Johnson syndrome. “It will be difficult to defend against that.”
Dr. Hardan is an adviser for Roche.
SAN FRANCISCO – About once a month, Antonio Y. Hardan, MD, and his colleagues at the Stanford (Calif.) University Autism and Developmental Disorders Clinic see an autistic child who is using or being prescribed marijuana.
“There are two types or responses we see with marijuana,” said Dr. Hardan, director of the clinic. “Most of the time, it calms the kid down for 2 or 3 hours, which is what you’d expect from marijuana. In one out of 10, I am hearing that parents see improvements in the core features of autism. We have several families who would swear by marijuana, but then 4 or 6 months later, they will change their mind and say it’s not helping as much.
Marijuana is just one of many alternatives families and doctors are trying to improve upon the usual medications and therapies for autism; the range of options being tried speaks to the desperation and frustration of families looking for help. There’s no home run so far; the common denominator for alternatives is anecdotal support but little evidence. Stanford has tried to address the evidence gap and continues to do so.
In 2012, for instance, Dr. Hardan and his colleagues reported a 33 patient study that found that N-acetylcysteine (NAC) – another hopeful candidate in recent years – might curb irritability (Biol Psychiatry. 2012 Jun 1;71[11]:956-61).
The tricky part about NAC is that it’s a dietary supplement, so you can’t be sure of what you’re getting in the store. There were questions at the talk about dose and formulations.
“The one we used in the study is made by BioAdvantex,” a Canadian company. “That’s the one that worked for us. One of the advantages is that every dose is wrapped individually.” NAC is an antioxidant, “so if you expose [it] to oxygen or light, it will get oxidized, and over time be less effective,” said Dr. Hardan, also a professor of psychiatry and behavioral sciences at the university.
Most of the time, NAC is very well tolerated, with only a little bit of flatulence and upset stomach.
Dr. Hardan and his colleagues started with 900 mg in one dose once a day for 4 weeks, then one dose twice a day for 4 weeks, followed by one dose three times daily, in children aged 2-12 years old. With experience, they are going faster now, cutting the 4 week interval to 2. “Some people are [even] more aggressive, which is okay,” he said.
Propranolol is another fashionable option, prescribed by a lot of doctors.
It’s not a new option; about 20 years ago, “we used it in very high dosages, 700-800 mg a day for self-injurious behavior. People wonder how you can go that high; above a dose of 200 mg, there is what we call an ‘escape phenomena’ where the heart will stop responding, and the effects on blood pressure and pulse are minimal,” Dr. Hardan said.
Interest in propranolol over the past 5 years has expanded to anxiety, sensory abnormalities, and other non-specific autism symptoms. “Unfortunately, there are no clinical trials to support that,” he said. The only evidence so far is from a functional MRI study in adults that suggested a little bit more efficient processing on a language task; further investigation is underway.
A lot of parents also are asking for oxytocin, and doctors are prescribing it. Someone in the audience wondered whether it had a role in everyday practice.
“Not at this time,” Dr. Hardan said. “I would suggest waiting a little bit until” results are reported from an ongoing trial. They are due soon, and there might be a subgroup of kids who benefit. Oxytocin seemed to help all-comers recognize facial cues.
Arginine vasopressin might do that, too, and be more specific for autism; Stanford is planning a study to look into it.
Attendees also wanted to know what to do about sleep problems, a common issue in autism.
“I’m aggressive in the treatment of insomnia, especially in single-parent households, because if the kid isn’t sleeping, the parent isn’t sleeping” and they may get irritable and moody, which raises the risk of abuse, Dr. Hardan said.
He starts with melatonin, 1 mg in the evening, and increases it by 1 mg every week to hit a target of 6 mg per night. He hasn’t seen much benefit of going higher. It’s important to remember that melatonin might take up to a week to see the full effect.
If melatonin fails, Dr. Hardan goes up the ladder. Diphenhydramine (Benadryl), benzodiazepines, trazodone (Oleptro), and mirtazapine (Remeron) are among the options. Rarely, there’s a need for quetiapine (Seroquel).
To counter benzodiazepine disinhibition, he asks parents to try them on a good day at home, so the effect of environmental stressors like going to the dentist can be divided out from the drug.
Dr. Hardan cautioned that there is “no evidence at this time to support the use of” lamotrigine (Lamictal). “Please don’t use it; somebody will end up developing” Stevens-Johnson syndrome. “It will be difficult to defend against that.”
Dr. Hardan is an adviser for Roche.
EXPERT ANALYSIS AT THE PSYCHOPHARMACOLOGY UPDATE INSTITUTE
Postpartum depression risk 20 times greater among women with depression history
Women with a history of depression have a risk of postpartum depression that is more than 20 times greater than women without such a history, according to Michael E. Silverman, PhD, and his associates. In addition, pre- and perinatal risk factors also raise the postpartum depression risk, they reported.
In a nationwide prospective cohort study, Dr. Silverman and his associates identified 707,701 women with live singleton births in Sweden from 1997-2008. Results showed that, compared with women without a history of depression, there was a statistically increased risk for postpartum depression in women with a history of depression (relative risk, 21.03; 95% confidence interval, 19.72-22.42).
Pregnancy length and depression history also proved significant in the mothers’ development of postpartum depression. The risk of postpartum depression, for example, was higher among women with a history of depression who gave birth before week 32 (RR, 1.12; 95% CI, 0.73-1.74), compared with women who gave birth before the 32nd week without a depression history (RR, 1.53; 95% CI, 1.12-2.10).
The existence of diabetic disease was another significant factor. Among women with gestational diabetes with a history of depression, the risk of postpartum depression was slightly higher (RR, 1.69; 95% CI, 1.18-2.43) than it was for women in that group without a depression history (RR, 1.67; 95% CI, 1.25-2.23). The differences were more dramatic among women with pregestational diabetes. Those with pregestational diabetes with a history of depression had a far greater risk of developing postpartum depression (RR, 1.49; 95% CI, 1.01-2.21) than did women with pregestational diabetes without a history of depression (RR, 1.16; 95% CI, 0.73-1.83), reported Dr. Silverman, of the department of psychiatry at the Icahn Medicine at Mount Sinai, New York, and his associates.
“For the first time, we show how maternal and obstetric risk factors for [postpartum depression] may differ between new mothers with and without a history of depression,” the investigators wrote. “Never shown before, some of the risks associated with obstetric and perinatal factors are modified by a history of depression, suggesting differences in the etiology of [postpartum depression] between women with and without a personal history of depression.”
Read the full study in Depression and Anxiety (doi: 10.1002/da.22597).
Women with a history of depression have a risk of postpartum depression that is more than 20 times greater than women without such a history, according to Michael E. Silverman, PhD, and his associates. In addition, pre- and perinatal risk factors also raise the postpartum depression risk, they reported.
In a nationwide prospective cohort study, Dr. Silverman and his associates identified 707,701 women with live singleton births in Sweden from 1997-2008. Results showed that, compared with women without a history of depression, there was a statistically increased risk for postpartum depression in women with a history of depression (relative risk, 21.03; 95% confidence interval, 19.72-22.42).
Pregnancy length and depression history also proved significant in the mothers’ development of postpartum depression. The risk of postpartum depression, for example, was higher among women with a history of depression who gave birth before week 32 (RR, 1.12; 95% CI, 0.73-1.74), compared with women who gave birth before the 32nd week without a depression history (RR, 1.53; 95% CI, 1.12-2.10).
The existence of diabetic disease was another significant factor. Among women with gestational diabetes with a history of depression, the risk of postpartum depression was slightly higher (RR, 1.69; 95% CI, 1.18-2.43) than it was for women in that group without a depression history (RR, 1.67; 95% CI, 1.25-2.23). The differences were more dramatic among women with pregestational diabetes. Those with pregestational diabetes with a history of depression had a far greater risk of developing postpartum depression (RR, 1.49; 95% CI, 1.01-2.21) than did women with pregestational diabetes without a history of depression (RR, 1.16; 95% CI, 0.73-1.83), reported Dr. Silverman, of the department of psychiatry at the Icahn Medicine at Mount Sinai, New York, and his associates.
“For the first time, we show how maternal and obstetric risk factors for [postpartum depression] may differ between new mothers with and without a history of depression,” the investigators wrote. “Never shown before, some of the risks associated with obstetric and perinatal factors are modified by a history of depression, suggesting differences in the etiology of [postpartum depression] between women with and without a personal history of depression.”
Read the full study in Depression and Anxiety (doi: 10.1002/da.22597).
Women with a history of depression have a risk of postpartum depression that is more than 20 times greater than women without such a history, according to Michael E. Silverman, PhD, and his associates. In addition, pre- and perinatal risk factors also raise the postpartum depression risk, they reported.
In a nationwide prospective cohort study, Dr. Silverman and his associates identified 707,701 women with live singleton births in Sweden from 1997-2008. Results showed that, compared with women without a history of depression, there was a statistically increased risk for postpartum depression in women with a history of depression (relative risk, 21.03; 95% confidence interval, 19.72-22.42).
Pregnancy length and depression history also proved significant in the mothers’ development of postpartum depression. The risk of postpartum depression, for example, was higher among women with a history of depression who gave birth before week 32 (RR, 1.12; 95% CI, 0.73-1.74), compared with women who gave birth before the 32nd week without a depression history (RR, 1.53; 95% CI, 1.12-2.10).
The existence of diabetic disease was another significant factor. Among women with gestational diabetes with a history of depression, the risk of postpartum depression was slightly higher (RR, 1.69; 95% CI, 1.18-2.43) than it was for women in that group without a depression history (RR, 1.67; 95% CI, 1.25-2.23). The differences were more dramatic among women with pregestational diabetes. Those with pregestational diabetes with a history of depression had a far greater risk of developing postpartum depression (RR, 1.49; 95% CI, 1.01-2.21) than did women with pregestational diabetes without a history of depression (RR, 1.16; 95% CI, 0.73-1.83), reported Dr. Silverman, of the department of psychiatry at the Icahn Medicine at Mount Sinai, New York, and his associates.
“For the first time, we show how maternal and obstetric risk factors for [postpartum depression] may differ between new mothers with and without a history of depression,” the investigators wrote. “Never shown before, some of the risks associated with obstetric and perinatal factors are modified by a history of depression, suggesting differences in the etiology of [postpartum depression] between women with and without a personal history of depression.”
Read the full study in Depression and Anxiety (doi: 10.1002/da.22597).
FROM DEPRESSION AND ANXIETY
Postop incentive spirometry had minimal impact on hypoxemia in bariatric surgery patients
The effect of incentive spirometry (IS) on postoperative hypoxemia in bariatric surgery patients was found to be insignificant, according to a randomized cohort study published in JAMA Surgery.
“At present, postoperative IS is considered the standard of care and is incorporated into standardized bariatric surgery recovery protocols,” wrote the authors of the study, led by Haddon Pantel, MD, of the Lahey Hospital and Medical Center in Burlington, Mass. “However, despite the ubiquitous use of IS in the postoperative period, data on its efficacy are conflicting, and high-quality evidence is lacking.” (JAMA Surg. doi:10.1001/jamasurg.2016.4981)
A total of 224 patients were evenly randomized into one of two cohorts; one cohort received no postoperative IS and acted as the control, while the other received postoperative IS. Patients from each of these cohorts were followed up at 6, 12, and 24 hours to measure SaO2 levels as a sign of hypoxemia, which was defined as a level of under 92%.
No significant differences were observed between the two cohorts at any of the three follow-up periods in terms of SaO2 levels. At 6 hours, hypoxemia incidence rates were 11.9% in the control group and 10.4% in the IS group (P = .72). At the 12-hour follow-up, the control group registered a 5.4% incidence rate, compared with 8.2% for those receiving postoperative IS (P = .40). And finally, at 24-hour follow-up, the control group had a 3.7% rate of hypoxemia, while those in the IS cohort had a 4.6% rate (P = .73). In addition, there were no significant differences observed in the average SaO2 levels between the two cohorts (P = .99, P = .40, and P = .69 at 6, 12, and 24 hours, respectively) nor was there a significantly higher rate of pulmonary complications in one cohort versus the other (P = .24).
The authors concluded, “With health care moving toward a more evidence-based, economically driven, and environmentally sustainable field, this study adds evidence to the concept that IS should not be universally used in all patients undergoing surgery and does not appear to be necessary in elective bariatric surgical procedures.”
The study was funded by Lahey Hospital and Medical Center’s department of general surgery; the authors reported no relevant financial disclosures.
The effect of incentive spirometry (IS) on postoperative hypoxemia in bariatric surgery patients was found to be insignificant, according to a randomized cohort study published in JAMA Surgery.
“At present, postoperative IS is considered the standard of care and is incorporated into standardized bariatric surgery recovery protocols,” wrote the authors of the study, led by Haddon Pantel, MD, of the Lahey Hospital and Medical Center in Burlington, Mass. “However, despite the ubiquitous use of IS in the postoperative period, data on its efficacy are conflicting, and high-quality evidence is lacking.” (JAMA Surg. doi:10.1001/jamasurg.2016.4981)
A total of 224 patients were evenly randomized into one of two cohorts; one cohort received no postoperative IS and acted as the control, while the other received postoperative IS. Patients from each of these cohorts were followed up at 6, 12, and 24 hours to measure SaO2 levels as a sign of hypoxemia, which was defined as a level of under 92%.
No significant differences were observed between the two cohorts at any of the three follow-up periods in terms of SaO2 levels. At 6 hours, hypoxemia incidence rates were 11.9% in the control group and 10.4% in the IS group (P = .72). At the 12-hour follow-up, the control group registered a 5.4% incidence rate, compared with 8.2% for those receiving postoperative IS (P = .40). And finally, at 24-hour follow-up, the control group had a 3.7% rate of hypoxemia, while those in the IS cohort had a 4.6% rate (P = .73). In addition, there were no significant differences observed in the average SaO2 levels between the two cohorts (P = .99, P = .40, and P = .69 at 6, 12, and 24 hours, respectively) nor was there a significantly higher rate of pulmonary complications in one cohort versus the other (P = .24).
The authors concluded, “With health care moving toward a more evidence-based, economically driven, and environmentally sustainable field, this study adds evidence to the concept that IS should not be universally used in all patients undergoing surgery and does not appear to be necessary in elective bariatric surgical procedures.”
The study was funded by Lahey Hospital and Medical Center’s department of general surgery; the authors reported no relevant financial disclosures.
The effect of incentive spirometry (IS) on postoperative hypoxemia in bariatric surgery patients was found to be insignificant, according to a randomized cohort study published in JAMA Surgery.
“At present, postoperative IS is considered the standard of care and is incorporated into standardized bariatric surgery recovery protocols,” wrote the authors of the study, led by Haddon Pantel, MD, of the Lahey Hospital and Medical Center in Burlington, Mass. “However, despite the ubiquitous use of IS in the postoperative period, data on its efficacy are conflicting, and high-quality evidence is lacking.” (JAMA Surg. doi:10.1001/jamasurg.2016.4981)
A total of 224 patients were evenly randomized into one of two cohorts; one cohort received no postoperative IS and acted as the control, while the other received postoperative IS. Patients from each of these cohorts were followed up at 6, 12, and 24 hours to measure SaO2 levels as a sign of hypoxemia, which was defined as a level of under 92%.
No significant differences were observed between the two cohorts at any of the three follow-up periods in terms of SaO2 levels. At 6 hours, hypoxemia incidence rates were 11.9% in the control group and 10.4% in the IS group (P = .72). At the 12-hour follow-up, the control group registered a 5.4% incidence rate, compared with 8.2% for those receiving postoperative IS (P = .40). And finally, at 24-hour follow-up, the control group had a 3.7% rate of hypoxemia, while those in the IS cohort had a 4.6% rate (P = .73). In addition, there were no significant differences observed in the average SaO2 levels between the two cohorts (P = .99, P = .40, and P = .69 at 6, 12, and 24 hours, respectively) nor was there a significantly higher rate of pulmonary complications in one cohort versus the other (P = .24).
The authors concluded, “With health care moving toward a more evidence-based, economically driven, and environmentally sustainable field, this study adds evidence to the concept that IS should not be universally used in all patients undergoing surgery and does not appear to be necessary in elective bariatric surgical procedures.”
The study was funded by Lahey Hospital and Medical Center’s department of general surgery; the authors reported no relevant financial disclosures.
FROM JAMA SURGERY
Key clinical point:
Major finding: No significant difference in hypoxemia frequency was found between postoperative IS and control cohorts at 6, 12, and 24-hour follow-ups (P = .72, .40, and .73, respectively).
Data source: A randomized, noninferiority cohort study of 224 bariatric surgery patients during May 2015 through June 2016.
Disclosures: Study funded by Lahey Hospital and Medical Center; authors reported no relevant financial disclosures.
MTX side effects limit patient use
Side effects in conjunction with inadequate disease control lead patients with plaque psoriasis to discontinue methotrexate (MTX) treatment, Dr. Marisol Otero and her colleagues reported.
The investigators identified 85 adult patients with plaque psoriasis from the Continuous Assessment of Psoriasis Treatment Use Registry With Methotrexate (MTX-CAPTURE) who had been treated with MTX for up to of 5.2 years. All had been started on MTX in accordance with Dutch and European guidelines.
Dose adjustments during treatment were made at physicians’ discretion and most patients (84) received folic acid supplements to protect against gastrointestinal side effects. Patients were required to have at least one follow up session with their physician during the study, according to Dr. Otero of the department of dermatology at Radboud University, Nijmegen, the Netherlands, and her colleagues.
At the end of 5 years, 55 patients (64.7%) had discontinued MTX, defined as cessation of MTX for more than 90 days or addition of another systemic psoriasis medication (Br J Dermatol. doi: 10.1111/bjd.15305).
Of the patients who discontinued treatment, 19 (34.5%) did so solely because of side effects, 14 (25.5%) discontinued because of lack of efficacy, and 7 (12.7%) cited the combination of side effects and ineffectiveness. Nine (16.4%) decided to end treatment for other reasons including personal decision, desire for pregnancy, and clinically inactive disease. Six (10.9%) were lost to for follow-up.
Side effects alone were the primary determinant in drug survival, with an overall drug survival rate for MTX of 1.8 years, Dr. Otero noted.
“It was remarkable that discontinuation due to side effects and ineffectiveness, were both common, while our hypothesis was that drug survival of MTX would be mainly limited by side effects,” the investigators said. “Side effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control solely.”
Side effects in conjunction with inadequate disease control lead patients with plaque psoriasis to discontinue methotrexate (MTX) treatment, Dr. Marisol Otero and her colleagues reported.
The investigators identified 85 adult patients with plaque psoriasis from the Continuous Assessment of Psoriasis Treatment Use Registry With Methotrexate (MTX-CAPTURE) who had been treated with MTX for up to of 5.2 years. All had been started on MTX in accordance with Dutch and European guidelines.
Dose adjustments during treatment were made at physicians’ discretion and most patients (84) received folic acid supplements to protect against gastrointestinal side effects. Patients were required to have at least one follow up session with their physician during the study, according to Dr. Otero of the department of dermatology at Radboud University, Nijmegen, the Netherlands, and her colleagues.
At the end of 5 years, 55 patients (64.7%) had discontinued MTX, defined as cessation of MTX for more than 90 days or addition of another systemic psoriasis medication (Br J Dermatol. doi: 10.1111/bjd.15305).
Of the patients who discontinued treatment, 19 (34.5%) did so solely because of side effects, 14 (25.5%) discontinued because of lack of efficacy, and 7 (12.7%) cited the combination of side effects and ineffectiveness. Nine (16.4%) decided to end treatment for other reasons including personal decision, desire for pregnancy, and clinically inactive disease. Six (10.9%) were lost to for follow-up.
Side effects alone were the primary determinant in drug survival, with an overall drug survival rate for MTX of 1.8 years, Dr. Otero noted.
“It was remarkable that discontinuation due to side effects and ineffectiveness, were both common, while our hypothesis was that drug survival of MTX would be mainly limited by side effects,” the investigators said. “Side effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control solely.”
Side effects in conjunction with inadequate disease control lead patients with plaque psoriasis to discontinue methotrexate (MTX) treatment, Dr. Marisol Otero and her colleagues reported.
The investigators identified 85 adult patients with plaque psoriasis from the Continuous Assessment of Psoriasis Treatment Use Registry With Methotrexate (MTX-CAPTURE) who had been treated with MTX for up to of 5.2 years. All had been started on MTX in accordance with Dutch and European guidelines.
Dose adjustments during treatment were made at physicians’ discretion and most patients (84) received folic acid supplements to protect against gastrointestinal side effects. Patients were required to have at least one follow up session with their physician during the study, according to Dr. Otero of the department of dermatology at Radboud University, Nijmegen, the Netherlands, and her colleagues.
At the end of 5 years, 55 patients (64.7%) had discontinued MTX, defined as cessation of MTX for more than 90 days or addition of another systemic psoriasis medication (Br J Dermatol. doi: 10.1111/bjd.15305).
Of the patients who discontinued treatment, 19 (34.5%) did so solely because of side effects, 14 (25.5%) discontinued because of lack of efficacy, and 7 (12.7%) cited the combination of side effects and ineffectiveness. Nine (16.4%) decided to end treatment for other reasons including personal decision, desire for pregnancy, and clinically inactive disease. Six (10.9%) were lost to for follow-up.
Side effects alone were the primary determinant in drug survival, with an overall drug survival rate for MTX of 1.8 years, Dr. Otero noted.
“It was remarkable that discontinuation due to side effects and ineffectiveness, were both common, while our hypothesis was that drug survival of MTX would be mainly limited by side effects,” the investigators said. “Side effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control solely.”
FROM THE BRITISH JOURNAL OF DERMATOLOGY
Key clinical point:
Major finding: More than one-third (34.5%) of patients stopped MTX because of side effects while more than a quarter (25.5%) did so due to lack of efficacy.
Data source: Analysis of 85 patients from a prospective noninterventional daily practice registry.
Disclosures: The study received no external funding. Dr. Otero has worked as a consultant for Eli Lilly. Other investigators reported consultancies and/or clinical trial work with multiple major pharmaceutical companies.
5% dextrose speeds induced-labor delivery
LAS VEGAS – Adding 5% dextrose to the hydrating solution given to women undergoing induced labor safely led to a median 76-minute decrease in labor duration in a single-center randomized study.
Normal saline with 5% dextrose “should be considered the default solute during labor induction in nulliparous women,” Josianne Paré, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine. “The uterus is a muscle, and glucose is its main energy substrate.”
During January 2013 to January 2015, women who met these criteria and required induction received either normal saline or normal saline plus 5% dextrose when they began their oxytocin drip, at a rate of 250 mL/hour.
Treatment with the assigned hydrating solutions continued until delivery or C-section. Participants averaged 28 years old, their average body mass index was 26 kg/m2 and average birth weight was about 3,450 g.
The study’s primary outcome was total duration of labor. This was a median of 423 minutes in 96 women who received dextrose and were available for analysis, and a median of 499 minutes in 97 evaluable women who received the saline control, a median difference of 76 minutes that was statistically significant, Dr. Paré reported. Most of the difference in labor duration happened during the first stage, which showed a median 70-minute reduction between the control group and the women receiving dextrose.
“These results support findings from prior studies. Women need glucose during labor,” Elliott Main, MD, commented in an interview. “There is no evidence for a need to exclude glucose from intravenous fluids. Adding some form of glucose is not standard practice today, but the time has come to do it, either by adding glucose to hydrating fluid or have women in labor eat and drink more,” said Dr. Main, medical director of the California Maternal Quality Care Collaborative in Stanford.
Dr. Paré reported having no financial disclosures.
[email protected]
On Twitter @mitchelzoler
LAS VEGAS – Adding 5% dextrose to the hydrating solution given to women undergoing induced labor safely led to a median 76-minute decrease in labor duration in a single-center randomized study.
Normal saline with 5% dextrose “should be considered the default solute during labor induction in nulliparous women,” Josianne Paré, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine. “The uterus is a muscle, and glucose is its main energy substrate.”
During January 2013 to January 2015, women who met these criteria and required induction received either normal saline or normal saline plus 5% dextrose when they began their oxytocin drip, at a rate of 250 mL/hour.
Treatment with the assigned hydrating solutions continued until delivery or C-section. Participants averaged 28 years old, their average body mass index was 26 kg/m2 and average birth weight was about 3,450 g.
The study’s primary outcome was total duration of labor. This was a median of 423 minutes in 96 women who received dextrose and were available for analysis, and a median of 499 minutes in 97 evaluable women who received the saline control, a median difference of 76 minutes that was statistically significant, Dr. Paré reported. Most of the difference in labor duration happened during the first stage, which showed a median 70-minute reduction between the control group and the women receiving dextrose.
“These results support findings from prior studies. Women need glucose during labor,” Elliott Main, MD, commented in an interview. “There is no evidence for a need to exclude glucose from intravenous fluids. Adding some form of glucose is not standard practice today, but the time has come to do it, either by adding glucose to hydrating fluid or have women in labor eat and drink more,” said Dr. Main, medical director of the California Maternal Quality Care Collaborative in Stanford.
Dr. Paré reported having no financial disclosures.
[email protected]
On Twitter @mitchelzoler
LAS VEGAS – Adding 5% dextrose to the hydrating solution given to women undergoing induced labor safely led to a median 76-minute decrease in labor duration in a single-center randomized study.
Normal saline with 5% dextrose “should be considered the default solute during labor induction in nulliparous women,” Josianne Paré, MD, said at the annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine. “The uterus is a muscle, and glucose is its main energy substrate.”
During January 2013 to January 2015, women who met these criteria and required induction received either normal saline or normal saline plus 5% dextrose when they began their oxytocin drip, at a rate of 250 mL/hour.
Treatment with the assigned hydrating solutions continued until delivery or C-section. Participants averaged 28 years old, their average body mass index was 26 kg/m2 and average birth weight was about 3,450 g.
The study’s primary outcome was total duration of labor. This was a median of 423 minutes in 96 women who received dextrose and were available for analysis, and a median of 499 minutes in 97 evaluable women who received the saline control, a median difference of 76 minutes that was statistically significant, Dr. Paré reported. Most of the difference in labor duration happened during the first stage, which showed a median 70-minute reduction between the control group and the women receiving dextrose.
“These results support findings from prior studies. Women need glucose during labor,” Elliott Main, MD, commented in an interview. “There is no evidence for a need to exclude glucose from intravenous fluids. Adding some form of glucose is not standard practice today, but the time has come to do it, either by adding glucose to hydrating fluid or have women in labor eat and drink more,” said Dr. Main, medical director of the California Maternal Quality Care Collaborative in Stanford.
Dr. Paré reported having no financial disclosures.
[email protected]
On Twitter @mitchelzoler
AT THE PREGNANCY MEETING
Key clinical point:
Major finding: Median labor duration fell by 76 minutes among women who received 5% dextrose, compared with controls.
Data source: DEXTRONS, a single-center, randomized study that enrolled 200 pregnant women.
Disclosures: Dr. Paré reported having no financial disclosures.
Universal cervical length screening reduces preterm birth rate
LAS VEGAS – Universal cervical length screening by transvaginal ultrasound in a low-risk cohort resulted in a significant reduction in spontaneous preterm births.
In a single-center retrospective cohort study of more than 13,000 deliveries, the overall preterm birth rate decreased from 3.8% to 2.4% on implementation of universal cervical length screening (P less than .001).
Screening reduced the numbers of both early and late preterm birth rates. Preterm births occurring earlier than 28 weeks’ gestation dropped from 0.3% to 0.1% (P = .04); preterm births before 34 weeks dropped from 1% to 0.5% (P less than .001); and preterm births before 37 weeks dropped from 2.5% to 1.8% (P = .004).
The data were presented by Alex Argyelan, MD, an ob.gyn. resident at St. Joseph Mercy Hospital–Ann Arbor, Mich., at the Annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Argyelan noted that the current Society for Maternal-Fetal Medicine (SMFM) position regarding cervical length screening is that it should not yet be universally mandated for singleton pregnancies without a prior history of preterm birth. However, a 2016 SMFM guideline stated, “Nonetheless, implementation of such a screening strategy can be viewed as reasonable and can be considered by individual practitioners.” This statement was made, he said, in recognition of the fact that “a sonographic short cervix is a powerful predictor of spontaneous preterm birth,” and that progesterone administration for gravid women with shortening cervixes can, for many, forestall spontaneous preterm labor.
First author Pooja Mittal Green, MD, a maternal-fetal medicine specialist at St. Joseph Mercy Hospital, and her associates looked at preterm delivery data before and after implementation of a universal cervical length screening protocol at a single tertiary referral center. The data collection period spanned from January 2013 to May 2014, with implementation of universal cervical length screening in October 2014.
A total of 13,396 women were included in the study, with a small minority of just 0.5% having experienced a prior spontaneous preterm birth. The mean patient age was just under 30 years; most patients were white, mirroring the demographics of the county where the study took place. Pre- and postintervention patient characteristics did not vary significantly.
Almost all patients agreed to cervical length screening by ultrasound, with the numbers climbing from 93% during the first year after implementing the universal screening protocol, to 99.2% in 2016.
All of the sonographers participating in the study were Cervical Length Education and Review (CLEAR) certified, and the institution’s lead sonographer carried out a ongoing quality assurance program.
A shortened cervix (25 mm or less) was found in a total of 114 women (1.7%) who underwent cervical length screening. According to the protocol, if maternal cervical length was 25 mm or less, women were offered treatment to attempt to stave off preterm delivery, according to the usual standard of care.
For women with no prior history of preterm delivery, treatment was vaginal progesterone. For women who had a prior preterm birth, cervical cerclage was offered, as well as vaginal progesterone if the patient was not already on 17-alpha-hydroxyprogesterone caproate.
The determination whether spontaneous preterm birth had occurred was made by reviewing labor and delivery birth logs, with a subsequent individual chart review to make sure that the delivery happened after either spontaneous labor or preterm premature rupture of membranes.
Only women who received prenatal care at the study institution were included in the study, and women who had not received any prenatal care were excluded.
Dr. Argyelan and his colleagues did not see any significant differences between the preterm and term delivery groups in maternal age, body mass index, or ethnicity.
“Among spontaneous preterm deliveries in low-risk women, the proportion of deliveries before 34 weeks was decreased” after the intervention, said Dr. Argyelan, who reported seeing a decrease from 28% early (less than 34 weeks’ gestation) preterm births before the intervention to 17% after the intervention.
In response to an audience question, Dr. Argyelan noted that his institution charges $186 for an ultrasound examination that includes assessment of cervical length, saying, “We have not had significant issues being reimbursed.”
Another audience member asked what the institution policy had been before the universal screening program was implemented. “Before the universal screening study, there was a policy of screening those with a history of preterm birth; also, if sonographers saw what looked like a short cervix on transabdominal exam, then they would do a transvaginal scan to further assess the cervix,” Dr. Argyelan said.
Dr. Argyelan reported having no financial disclosures.
[email protected]
On Twitter @karioakes
LAS VEGAS – Universal cervical length screening by transvaginal ultrasound in a low-risk cohort resulted in a significant reduction in spontaneous preterm births.
In a single-center retrospective cohort study of more than 13,000 deliveries, the overall preterm birth rate decreased from 3.8% to 2.4% on implementation of universal cervical length screening (P less than .001).
Screening reduced the numbers of both early and late preterm birth rates. Preterm births occurring earlier than 28 weeks’ gestation dropped from 0.3% to 0.1% (P = .04); preterm births before 34 weeks dropped from 1% to 0.5% (P less than .001); and preterm births before 37 weeks dropped from 2.5% to 1.8% (P = .004).
The data were presented by Alex Argyelan, MD, an ob.gyn. resident at St. Joseph Mercy Hospital–Ann Arbor, Mich., at the Annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Argyelan noted that the current Society for Maternal-Fetal Medicine (SMFM) position regarding cervical length screening is that it should not yet be universally mandated for singleton pregnancies without a prior history of preterm birth. However, a 2016 SMFM guideline stated, “Nonetheless, implementation of such a screening strategy can be viewed as reasonable and can be considered by individual practitioners.” This statement was made, he said, in recognition of the fact that “a sonographic short cervix is a powerful predictor of spontaneous preterm birth,” and that progesterone administration for gravid women with shortening cervixes can, for many, forestall spontaneous preterm labor.
First author Pooja Mittal Green, MD, a maternal-fetal medicine specialist at St. Joseph Mercy Hospital, and her associates looked at preterm delivery data before and after implementation of a universal cervical length screening protocol at a single tertiary referral center. The data collection period spanned from January 2013 to May 2014, with implementation of universal cervical length screening in October 2014.
A total of 13,396 women were included in the study, with a small minority of just 0.5% having experienced a prior spontaneous preterm birth. The mean patient age was just under 30 years; most patients were white, mirroring the demographics of the county where the study took place. Pre- and postintervention patient characteristics did not vary significantly.
Almost all patients agreed to cervical length screening by ultrasound, with the numbers climbing from 93% during the first year after implementing the universal screening protocol, to 99.2% in 2016.
All of the sonographers participating in the study were Cervical Length Education and Review (CLEAR) certified, and the institution’s lead sonographer carried out a ongoing quality assurance program.
A shortened cervix (25 mm or less) was found in a total of 114 women (1.7%) who underwent cervical length screening. According to the protocol, if maternal cervical length was 25 mm or less, women were offered treatment to attempt to stave off preterm delivery, according to the usual standard of care.
For women with no prior history of preterm delivery, treatment was vaginal progesterone. For women who had a prior preterm birth, cervical cerclage was offered, as well as vaginal progesterone if the patient was not already on 17-alpha-hydroxyprogesterone caproate.
The determination whether spontaneous preterm birth had occurred was made by reviewing labor and delivery birth logs, with a subsequent individual chart review to make sure that the delivery happened after either spontaneous labor or preterm premature rupture of membranes.
Only women who received prenatal care at the study institution were included in the study, and women who had not received any prenatal care were excluded.
Dr. Argyelan and his colleagues did not see any significant differences between the preterm and term delivery groups in maternal age, body mass index, or ethnicity.
“Among spontaneous preterm deliveries in low-risk women, the proportion of deliveries before 34 weeks was decreased” after the intervention, said Dr. Argyelan, who reported seeing a decrease from 28% early (less than 34 weeks’ gestation) preterm births before the intervention to 17% after the intervention.
In response to an audience question, Dr. Argyelan noted that his institution charges $186 for an ultrasound examination that includes assessment of cervical length, saying, “We have not had significant issues being reimbursed.”
Another audience member asked what the institution policy had been before the universal screening program was implemented. “Before the universal screening study, there was a policy of screening those with a history of preterm birth; also, if sonographers saw what looked like a short cervix on transabdominal exam, then they would do a transvaginal scan to further assess the cervix,” Dr. Argyelan said.
Dr. Argyelan reported having no financial disclosures.
[email protected]
On Twitter @karioakes
LAS VEGAS – Universal cervical length screening by transvaginal ultrasound in a low-risk cohort resulted in a significant reduction in spontaneous preterm births.
In a single-center retrospective cohort study of more than 13,000 deliveries, the overall preterm birth rate decreased from 3.8% to 2.4% on implementation of universal cervical length screening (P less than .001).
Screening reduced the numbers of both early and late preterm birth rates. Preterm births occurring earlier than 28 weeks’ gestation dropped from 0.3% to 0.1% (P = .04); preterm births before 34 weeks dropped from 1% to 0.5% (P less than .001); and preterm births before 37 weeks dropped from 2.5% to 1.8% (P = .004).
The data were presented by Alex Argyelan, MD, an ob.gyn. resident at St. Joseph Mercy Hospital–Ann Arbor, Mich., at the Annual Pregnancy Meeting sponsored by the Society for Maternal-Fetal Medicine. Dr. Argyelan noted that the current Society for Maternal-Fetal Medicine (SMFM) position regarding cervical length screening is that it should not yet be universally mandated for singleton pregnancies without a prior history of preterm birth. However, a 2016 SMFM guideline stated, “Nonetheless, implementation of such a screening strategy can be viewed as reasonable and can be considered by individual practitioners.” This statement was made, he said, in recognition of the fact that “a sonographic short cervix is a powerful predictor of spontaneous preterm birth,” and that progesterone administration for gravid women with shortening cervixes can, for many, forestall spontaneous preterm labor.
First author Pooja Mittal Green, MD, a maternal-fetal medicine specialist at St. Joseph Mercy Hospital, and her associates looked at preterm delivery data before and after implementation of a universal cervical length screening protocol at a single tertiary referral center. The data collection period spanned from January 2013 to May 2014, with implementation of universal cervical length screening in October 2014.
A total of 13,396 women were included in the study, with a small minority of just 0.5% having experienced a prior spontaneous preterm birth. The mean patient age was just under 30 years; most patients were white, mirroring the demographics of the county where the study took place. Pre- and postintervention patient characteristics did not vary significantly.
Almost all patients agreed to cervical length screening by ultrasound, with the numbers climbing from 93% during the first year after implementing the universal screening protocol, to 99.2% in 2016.
All of the sonographers participating in the study were Cervical Length Education and Review (CLEAR) certified, and the institution’s lead sonographer carried out a ongoing quality assurance program.
A shortened cervix (25 mm or less) was found in a total of 114 women (1.7%) who underwent cervical length screening. According to the protocol, if maternal cervical length was 25 mm or less, women were offered treatment to attempt to stave off preterm delivery, according to the usual standard of care.
For women with no prior history of preterm delivery, treatment was vaginal progesterone. For women who had a prior preterm birth, cervical cerclage was offered, as well as vaginal progesterone if the patient was not already on 17-alpha-hydroxyprogesterone caproate.
The determination whether spontaneous preterm birth had occurred was made by reviewing labor and delivery birth logs, with a subsequent individual chart review to make sure that the delivery happened after either spontaneous labor or preterm premature rupture of membranes.
Only women who received prenatal care at the study institution were included in the study, and women who had not received any prenatal care were excluded.
Dr. Argyelan and his colleagues did not see any significant differences between the preterm and term delivery groups in maternal age, body mass index, or ethnicity.
“Among spontaneous preterm deliveries in low-risk women, the proportion of deliveries before 34 weeks was decreased” after the intervention, said Dr. Argyelan, who reported seeing a decrease from 28% early (less than 34 weeks’ gestation) preterm births before the intervention to 17% after the intervention.
In response to an audience question, Dr. Argyelan noted that his institution charges $186 for an ultrasound examination that includes assessment of cervical length, saying, “We have not had significant issues being reimbursed.”
Another audience member asked what the institution policy had been before the universal screening program was implemented. “Before the universal screening study, there was a policy of screening those with a history of preterm birth; also, if sonographers saw what looked like a short cervix on transabdominal exam, then they would do a transvaginal scan to further assess the cervix,” Dr. Argyelan said.
Dr. Argyelan reported having no financial disclosures.
[email protected]
On Twitter @karioakes
AT THE ANNUAL PREGNANCY MEETING
Key clinical point:
Major finding: Preterm births dropped from 3.8% to 2.4% (P less than .001) after implementing a universal cervical length screening program.
Data source: Retrospective single-site cohort study of 13,396 singleton pregnancies.
Disclosures: Dr. Argyelan reported having no financial disclosures.
CHMP recommends lenalidomide maintenance
Photo courtesy of Celgene
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended a new indication for lenalidomide (Revlimid®).
The CHMP advised the European Commission (EC) to approve the use of lenalidomide as maintenance therapy in adults who had newly diagnosed multiple myeloma (MM) prior to receiving an autologous stem cell transplant (ASCT).
If approved by the EC, lenalidomide will be the first licensed maintenance treatment available to this patient population in the European Union.
The EC, which generally follows the CHMP’s recommendations, is expected to make its final decision on this use of lenalidomide in approximately 2 months.
If approval is granted, detailed conditions for the use of lenalidomide will be described in the Summary of Product Characteristics, which will be published in the revised European Public Assessment Report.
Lenalidomide is a product of Celgene.
The CHMP’s recommendation to approve lenalidomide as maintenance in MM was based on the results of 2 cooperative group-led studies, CALGB 10010410 and IFM 2005-0211. Results from both studies were published in NEJM in May 2012.
CALGB 100104 was a phase 3, double-blind study of 460 patients with newly diagnosed MM undergoing ASCT. The patients received continuous daily treatment with lenalidomide or placebo until relapse.
IFM 2005-02 was a phase 3, double-blind study of 614 patients newly diagnosed with MM. The patients were randomized to receive a 2-month consolidation regimen post-ASCT of lenalidomide monotherapy, followed by continuous daily treatment with lenalidomide or placebo until relapse.
“Studies show that maintenance treatment after ASCT with Revlimid may help control residual malignant cells and delay tumor growth by enhancing immune function,” said Michel Attal, MD, of the Institut Universitaire du Cancer Toulouse Oncopole and Institut Claudius Regaud in France.
“Our primary goal is to delay disease progression for as long as possible, and we have seen in several independent studies that Revlimid maintenance after ASCT can halve the risk of disease progression by sustaining the response.” 
Photo courtesy of Celgene
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended a new indication for lenalidomide (Revlimid®).
The CHMP advised the European Commission (EC) to approve the use of lenalidomide as maintenance therapy in adults who had newly diagnosed multiple myeloma (MM) prior to receiving an autologous stem cell transplant (ASCT).
If approved by the EC, lenalidomide will be the first licensed maintenance treatment available to this patient population in the European Union.
The EC, which generally follows the CHMP’s recommendations, is expected to make its final decision on this use of lenalidomide in approximately 2 months.
If approval is granted, detailed conditions for the use of lenalidomide will be described in the Summary of Product Characteristics, which will be published in the revised European Public Assessment Report.
Lenalidomide is a product of Celgene.
The CHMP’s recommendation to approve lenalidomide as maintenance in MM was based on the results of 2 cooperative group-led studies, CALGB 10010410 and IFM 2005-0211. Results from both studies were published in NEJM in May 2012.
CALGB 100104 was a phase 3, double-blind study of 460 patients with newly diagnosed MM undergoing ASCT. The patients received continuous daily treatment with lenalidomide or placebo until relapse.
IFM 2005-02 was a phase 3, double-blind study of 614 patients newly diagnosed with MM. The patients were randomized to receive a 2-month consolidation regimen post-ASCT of lenalidomide monotherapy, followed by continuous daily treatment with lenalidomide or placebo until relapse.
“Studies show that maintenance treatment after ASCT with Revlimid may help control residual malignant cells and delay tumor growth by enhancing immune function,” said Michel Attal, MD, of the Institut Universitaire du Cancer Toulouse Oncopole and Institut Claudius Regaud in France.
“Our primary goal is to delay disease progression for as long as possible, and we have seen in several independent studies that Revlimid maintenance after ASCT can halve the risk of disease progression by sustaining the response.”
Photo courtesy of Celgene
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended a new indication for lenalidomide (Revlimid®).
The CHMP advised the European Commission (EC) to approve the use of lenalidomide as maintenance therapy in adults who had newly diagnosed multiple myeloma (MM) prior to receiving an autologous stem cell transplant (ASCT).
If approved by the EC, lenalidomide will be the first licensed maintenance treatment available to this patient population in the European Union.
The EC, which generally follows the CHMP’s recommendations, is expected to make its final decision on this use of lenalidomide in approximately 2 months.
If approval is granted, detailed conditions for the use of lenalidomide will be described in the Summary of Product Characteristics, which will be published in the revised European Public Assessment Report.
Lenalidomide is a product of Celgene.
The CHMP’s recommendation to approve lenalidomide as maintenance in MM was based on the results of 2 cooperative group-led studies, CALGB 10010410 and IFM 2005-0211. Results from both studies were published in NEJM in May 2012.
CALGB 100104 was a phase 3, double-blind study of 460 patients with newly diagnosed MM undergoing ASCT. The patients received continuous daily treatment with lenalidomide or placebo until relapse.
IFM 2005-02 was a phase 3, double-blind study of 614 patients newly diagnosed with MM. The patients were randomized to receive a 2-month consolidation regimen post-ASCT of lenalidomide monotherapy, followed by continuous daily treatment with lenalidomide or placebo until relapse.
“Studies show that maintenance treatment after ASCT with Revlimid may help control residual malignant cells and delay tumor growth by enhancing immune function,” said Michel Attal, MD, of the Institut Universitaire du Cancer Toulouse Oncopole and Institut Claudius Regaud in France.
“Our primary goal is to delay disease progression for as long as possible, and we have seen in several independent studies that Revlimid maintenance after ASCT can halve the risk of disease progression by sustaining the response.”
Tips for Living With Suspected CTE
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Migraine Increases the Risk of Perioperative Ischemic Stroke
Patients who undergo surgery have an increased risk of perioperative ischemic stroke if they have a history of migraine, according to a prospective study published January 10 in the BMJ. Surgical patients with a history of migraine also have an increased 30-day hospital readmission rate, compared with patients without migraine.
“Understanding this risk period offers unique opportunities to study ischemic stroke in migraine and might result in treatment considerations for patients at risk who are not undergoing surgical intervention,” said Matthias Eikermann, MD, PhD, Associate Professor of Anesthesia at Harvard Medical School in Boston, and colleagues. “An individual perioperative risk assessment for perioperative ischemic stroke in patients with migraine undergoing surgery may be crucial.” 
Dr. Eikermann and colleagues conducted a prospective hospital registry study that encompassed 124,558 patients who underwent surgery at Massachusetts General Hospital and two community hospitals in Massachusetts between January 2007 and August 2014. The researchers determined participants’ history of migraine and migraine aura status using ICD-9 diagnosis codes. The primary outcome was perioperative ischemic stroke within 30 days after surgery. The secondary outcome was hospital readmission within 30 days of discharge.
The mean age of participants was 52.6. Approximately 55% of patients were women. The investigators identified 10,179 (8.2%) patients with migraine, of whom 1,278 (12.6%) had migraine with aura. Compared with participants without migraine, migraineurs were more often female, were younger, and had an overall lower frequency of vascular risk factors.
Among the 124,558 patients who underwent surgery, the investigators observed 771 (0.6%) perioperative ischemic strokes. Of all patients with perioperative ischemic stroke, 89 (11.5%) had migraine. Among migraineurs, 18 (2.3%) had migraine with aura, and 71 (9.2%) had migraine without aura. Patients with migraine had an increased risk for perioperative ischemic stroke, compared with patients without migraine (adjusted odds ratio, 1.75). The risk of ischemic stroke was higher for patients with migraine with aura (adjusted odds ratio, 2.61), but also was apparent for migraine without aura (adjusted odds ratio, 1.62), compared with surgical patients without migraine.
Dr. Eikermann and colleagues predicted that 2.4 ischemic strokes would occur for every 1,000 surgical patients. This risk increased to 4.3 strokes for every 1,000 patients with migraine. Stratified by migraine with aura status, these numbers are 3.9 strokes for migraine without aura and 6.3 strokes for migraine with aura.
A total of 10,088 participants were readmitted to the hospital within 30 days. The 30-day hospital readmission rate was higher for patients with migraine than for those with no migraine (adjusted odds ratio, 1.31). Migraine with aura (adjusted odds ratio, 1.59) and migraine without aura (adjusted odds ratio, 1.27) were associated with a higher risk of 30-day hospital readmission, compared with patients without migraine.
“The use of high-dose vasopressors during surgery, as well a history of a possible right-to-left shunt, may represent modifiable risk factors for perioperative ischemic stroke in patients with migraine with aura,” said Dr. Eikermann. “Early detection of symptoms of stroke through close postoperative monitoring of patients at high risk should be crucial to optimize the value of perioperative care in patients with migraine.”
—Erik Greb
Suggested Reading
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017 Jan 10;356:i6635.
Patients who undergo surgery have an increased risk of perioperative ischemic stroke if they have a history of migraine, according to a prospective study published January 10 in the BMJ. Surgical patients with a history of migraine also have an increased 30-day hospital readmission rate, compared with patients without migraine.
“Understanding this risk period offers unique opportunities to study ischemic stroke in migraine and might result in treatment considerations for patients at risk who are not undergoing surgical intervention,” said Matthias Eikermann, MD, PhD, Associate Professor of Anesthesia at Harvard Medical School in Boston, and colleagues. “An individual perioperative risk assessment for perioperative ischemic stroke in patients with migraine undergoing surgery may be crucial.”
Dr. Eikermann and colleagues conducted a prospective hospital registry study that encompassed 124,558 patients who underwent surgery at Massachusetts General Hospital and two community hospitals in Massachusetts between January 2007 and August 2014. The researchers determined participants’ history of migraine and migraine aura status using ICD-9 diagnosis codes. The primary outcome was perioperative ischemic stroke within 30 days after surgery. The secondary outcome was hospital readmission within 30 days of discharge.
The mean age of participants was 52.6. Approximately 55% of patients were women. The investigators identified 10,179 (8.2%) patients with migraine, of whom 1,278 (12.6%) had migraine with aura. Compared with participants without migraine, migraineurs were more often female, were younger, and had an overall lower frequency of vascular risk factors.
Among the 124,558 patients who underwent surgery, the investigators observed 771 (0.6%) perioperative ischemic strokes. Of all patients with perioperative ischemic stroke, 89 (11.5%) had migraine. Among migraineurs, 18 (2.3%) had migraine with aura, and 71 (9.2%) had migraine without aura. Patients with migraine had an increased risk for perioperative ischemic stroke, compared with patients without migraine (adjusted odds ratio, 1.75). The risk of ischemic stroke was higher for patients with migraine with aura (adjusted odds ratio, 2.61), but also was apparent for migraine without aura (adjusted odds ratio, 1.62), compared with surgical patients without migraine.
Dr. Eikermann and colleagues predicted that 2.4 ischemic strokes would occur for every 1,000 surgical patients. This risk increased to 4.3 strokes for every 1,000 patients with migraine. Stratified by migraine with aura status, these numbers are 3.9 strokes for migraine without aura and 6.3 strokes for migraine with aura.
A total of 10,088 participants were readmitted to the hospital within 30 days. The 30-day hospital readmission rate was higher for patients with migraine than for those with no migraine (adjusted odds ratio, 1.31). Migraine with aura (adjusted odds ratio, 1.59) and migraine without aura (adjusted odds ratio, 1.27) were associated with a higher risk of 30-day hospital readmission, compared with patients without migraine.
“The use of high-dose vasopressors during surgery, as well a history of a possible right-to-left shunt, may represent modifiable risk factors for perioperative ischemic stroke in patients with migraine with aura,” said Dr. Eikermann. “Early detection of symptoms of stroke through close postoperative monitoring of patients at high risk should be crucial to optimize the value of perioperative care in patients with migraine.”
—Erik Greb
Suggested Reading
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017 Jan 10;356:i6635.
Patients who undergo surgery have an increased risk of perioperative ischemic stroke if they have a history of migraine, according to a prospective study published January 10 in the BMJ. Surgical patients with a history of migraine also have an increased 30-day hospital readmission rate, compared with patients without migraine.
“Understanding this risk period offers unique opportunities to study ischemic stroke in migraine and might result in treatment considerations for patients at risk who are not undergoing surgical intervention,” said Matthias Eikermann, MD, PhD, Associate Professor of Anesthesia at Harvard Medical School in Boston, and colleagues. “An individual perioperative risk assessment for perioperative ischemic stroke in patients with migraine undergoing surgery may be crucial.”
Dr. Eikermann and colleagues conducted a prospective hospital registry study that encompassed 124,558 patients who underwent surgery at Massachusetts General Hospital and two community hospitals in Massachusetts between January 2007 and August 2014. The researchers determined participants’ history of migraine and migraine aura status using ICD-9 diagnosis codes. The primary outcome was perioperative ischemic stroke within 30 days after surgery. The secondary outcome was hospital readmission within 30 days of discharge.
The mean age of participants was 52.6. Approximately 55% of patients were women. The investigators identified 10,179 (8.2%) patients with migraine, of whom 1,278 (12.6%) had migraine with aura. Compared with participants without migraine, migraineurs were more often female, were younger, and had an overall lower frequency of vascular risk factors.
Among the 124,558 patients who underwent surgery, the investigators observed 771 (0.6%) perioperative ischemic strokes. Of all patients with perioperative ischemic stroke, 89 (11.5%) had migraine. Among migraineurs, 18 (2.3%) had migraine with aura, and 71 (9.2%) had migraine without aura. Patients with migraine had an increased risk for perioperative ischemic stroke, compared with patients without migraine (adjusted odds ratio, 1.75). The risk of ischemic stroke was higher for patients with migraine with aura (adjusted odds ratio, 2.61), but also was apparent for migraine without aura (adjusted odds ratio, 1.62), compared with surgical patients without migraine.
Dr. Eikermann and colleagues predicted that 2.4 ischemic strokes would occur for every 1,000 surgical patients. This risk increased to 4.3 strokes for every 1,000 patients with migraine. Stratified by migraine with aura status, these numbers are 3.9 strokes for migraine without aura and 6.3 strokes for migraine with aura.
A total of 10,088 participants were readmitted to the hospital within 30 days. The 30-day hospital readmission rate was higher for patients with migraine than for those with no migraine (adjusted odds ratio, 1.31). Migraine with aura (adjusted odds ratio, 1.59) and migraine without aura (adjusted odds ratio, 1.27) were associated with a higher risk of 30-day hospital readmission, compared with patients without migraine.
“The use of high-dose vasopressors during surgery, as well a history of a possible right-to-left shunt, may represent modifiable risk factors for perioperative ischemic stroke in patients with migraine with aura,” said Dr. Eikermann. “Early detection of symptoms of stroke through close postoperative monitoring of patients at high risk should be crucial to optimize the value of perioperative care in patients with migraine.”
—Erik Greb
Suggested Reading
Timm FP, Houle TT, Grabitz SD, et al. Migraine and risk of perioperative ischemic stroke and hospital readmission: hospital based registry study. BMJ. 2017 Jan 10;356:i6635.
Mobile Devices May Provide Accurate Seizure Detection and Help Prevent SUDEP
HOUSTON—Mobile or wearable devices that observe autonomic and motor changes may provide seizure detection, according to an overview presented at the 70th Annual Meeting of the American Epilepsy Society. Devices that monitor heart rate, electrodermal changes, and electromyogram (EMG) changes also may provide accurate detection of convulsive seizures. Many such devices are in development, and some already are available. They may be convenient for patients to use and could provide opportunities for interventions to prevent sudden unexpected death in epilepsy (SUDEP).
What Do Patients Want?
In 2015, Hoppe and colleagues published the results of their survey of patients’ preferences for automated seizure-detection devices. The authors found that patients want convenient devices such as wearable wristbands, but do not want devices that are conspicuous. Patients want devices that perform automatic seizure registration and make emergency calls to family members or caregivers. They do not, however, want devices that notify their doctors automatically about seizures, preferring to maintain control of their own medical data. On the other hand, patients do want to get help during medical appointments with controlling and using the devices. Finally, patients want devices that predict seizures, but this task “probably requires intracranial recording,” said Gregory Krauss, MD, Professor of Neurology at Johns Hopkins University School of Medicine in Baltimore. 
Another survey asked patients about the accuracy that they wanted from these devices. One survey suggested that patients would accept a false-positive or false-negative rate of less than 25%. Seizure-free patients would accept a false-positive rate of less than one per week. Patients with recurring seizures would accept a higher false-positive rate. “Most patients said [that] as long as the ratio of false detections to true detections was not more than 1:1, they would find that acceptable,” said Dr. Krauss.
Patients also want rapid detection of seizures so that they can protect themselves or quickly get help. “The majority of patients would like detection to occur with alerting within one minute” of seizure onset, said Dr. Krauss. Some patients want detection to occur within 30 seconds of seizure onset, and about 14% of patients said that detection within three minutes of onset would be sufficient.
Investigators have pursued various methods for seizure detection. The major methods are physiologic (eg, heart rate, pulse oximetry, and electrodermal activity), motion-related (eg, accelerometers, mattress sensors, EMG, and video motion detection), and responsive testing (eg, testing memory and responsiveness). The best technique may be to combine several of these methods to minimize the rate of false positives, said Dr. Krauss.
SmartWatch
One device that currently is available is SmartWatch, which is manufactured by SmartMonitor. The SmartWatch device is a wrist accelerometer that predominantly detects convulsive seizures. Data from epilepsy monitoring units (EMUs) on the device’s efficacy have been mixed. In a Stanford University study, SmartWatch recorded 62 seizures in 27 patients. Nine patients had 13 tonic–clonic seizures, and the device detected 12 of them. The device had a false positive rate of 87%. In a University of Tennessee study involving 41 patients who had 191 seizures, the SmartWatch device detected 31% of tonic–clonic seizures. These studies suggest that the device has “somewhat limited sensitivity without individualizing settings,” and its accuracy during real-world use is unclear, said Dr. Krauss.
Embrace Watch
The device furthest along in development is Embrace Watch, which is being designed by Empatica. Embrace Watch is a smart watch that performs electrodermal and accelerometer measurements and is connected to a smart phone. It uses an app that graphically displays information about the user’s activity, stress level, and sleep. The watch is intended to detect convulsive seizures and send alerts to caregivers.
One reason that Embrace Watch measures electrodermal activity is that the latter correlates with postictal EEG suppression. Research indicates that postictal generalized EEG suppression corresponds with the risk of SUDEP. “That [finding] raises the possibility that the Empatica device may be useful for intervening in SUDEP,” said Dr. Krauss.
An ongoing study is evaluating Embrace Watch’s efficacy in an EMU. Investigators collected video EEG data for 69 patients and monitored electrodermal activity and movement with the Embrace Watch. The investigators reviewed the detection of 55 convulsive seizures in 22 patients. They tested two classifier models, which were different combinations of electrodermal activity and heart rate changes. One classifier model had 100% sensitivity, but a moderately high rate of false alarms (1.26/day). The other classifier model had a sensitivity of 95% and a rate of 0.2 false alarms per day, which may be acceptable for a patient with uncontrolled seizures, said Dr. Krauss. A separate case study suggests that Embrace Watch accurately detects major seizures in patients with Dravet syndrome.
Brain Sentinel
The FDA is reviewing the Brain Sentinel seizure-monitoring system, which uses EMG recordings to detect convulsive seizures. The device takes advantage of a characteristic firing pattern on EMG that is associated with convulsive seizures. Research has indicated that, when used properly, the system detects seizures with near-perfect accuracy. The system’s accuracy was slightly higher in adults than in a group of adults and children. The average time between seizure onset and alarm was 5.34 seconds in adults and 7.70 seconds in adults and children. The rate of false positives per eight-hour period was 0.51 in adults and 0.48 in adults and children. Most false alarms occurred in a minority of participants. “This device is probably going to be effective for detecting convulsive seizures in patients with uncontrolled epilepsy,” said Dr. Krauss.
EpiWatch App
Dr. Krauss and Nathan Crone, MD, Professor of Neurology at Johns Hopkins University School of Medicine, are developing a seizure-detection app called EpiWatch for use on the Apple Watch. Their objective is to use the Apple Watch’s ability to monitor heart rate, movement, and position to detect seizures. Through the Apple Watch’s user interface, the app asks patients to label seizures and attempts to reduce the number of false detections. During a seizure, the app tests the user’s responsiveness by asking him or her to tap the watch. The test occurs at 20 seconds after seizure onset and at one-minute intervals thereafter. If the user is responsive, the app administers a test of working memory that involves repeating a series of random numbers. At 10 minutes after the seizure ends, the app asks the user whether he or she had had a seizure, whether he or she had had an aura, and whether he or she had lost awareness. These data are logged into a journal that can be transmitted.
Drs. Krauss and Crone are using Apple ResearchKit to study the app’s efficacy. They have enrolled approximately 700 participants in the study, and about 40% of them were able to activate the app during a seizure. The seizure types recorded so far are representative of those of the general US population of patients with epilepsy. Approximately 30% of participants had a 50% increase in heart rate during their seizure. About two-thirds of patients had a 30% increase in heart rate. A significant number of patients with complex partial seizures had decreases in heart rate during their seizure. “Heart rate alone would probably not be a sensitive screening technique for seizures, but it could be one component of an algorithm,” said Dr. Krauss.
Can These Devices Prevent SUDEP?
Many of these devices were designed with the goal of enabling interventions, particularly during severe nocturnal convulsive seizures, to prevent SUDEP. The current understanding of SUDEP provides grounds for optimism that such interventions could be achieved, said Dr. Krauss. Many patients with tonic–clonic seizures have oxygen saturation, postictal generalized EEG suppression, and autonomic alterations. If patients become immobile during a seizure and are lying face down, they may become asphyxiated. “The question is whether we can intervene at that point to prevent the subsequent cardiac arrhythmias which lead to their death,” said Dr. Krauss. A caregiver, for example, could turn a patient on his or her side and stimulate him or her to promote breathing. If the caregiver finds the patient at a later time after seizure onset, he or she could attempt resuscitation. “This is our general concept of perhaps how SUDEP intervention could be performed using mobile device detectors,” Dr. Krauss concluded.
—Erik Greb
Suggested Reading
Hoppe C, Feldmann M, Blachut B, et al. Novel techniques for automated seizure registration: Patients’ wants and needs. Epilepsy Behav. 2015;52(Pt A):1-7.
Lhatoo SD, Nei M, Raghavan M, et al. Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures. Epilepsia. 2016;57(7):1161-1168.
Van de Vel A, Smets K, Wouters K, Ceulemans B. Automated non-EEG based seizure detection: Do users have a say? Epilepsy Behav. 2016;62:121-128.
Velez M, Fisher RS, Bartlett V, Le S. Tracking generalized tonic-clonic seizures with a wrist accelerometer linked to an online database. Seizure. 2016;39:13-18.
HOUSTON—Mobile or wearable devices that observe autonomic and motor changes may provide seizure detection, according to an overview presented at the 70th Annual Meeting of the American Epilepsy Society. Devices that monitor heart rate, electrodermal changes, and electromyogram (EMG) changes also may provide accurate detection of convulsive seizures. Many such devices are in development, and some already are available. They may be convenient for patients to use and could provide opportunities for interventions to prevent sudden unexpected death in epilepsy (SUDEP).
What Do Patients Want?
In 2015, Hoppe and colleagues published the results of their survey of patients’ preferences for automated seizure-detection devices. The authors found that patients want convenient devices such as wearable wristbands, but do not want devices that are conspicuous. Patients want devices that perform automatic seizure registration and make emergency calls to family members or caregivers. They do not, however, want devices that notify their doctors automatically about seizures, preferring to maintain control of their own medical data. On the other hand, patients do want to get help during medical appointments with controlling and using the devices. Finally, patients want devices that predict seizures, but this task “probably requires intracranial recording,” said Gregory Krauss, MD, Professor of Neurology at Johns Hopkins University School of Medicine in Baltimore.
Another survey asked patients about the accuracy that they wanted from these devices. One survey suggested that patients would accept a false-positive or false-negative rate of less than 25%. Seizure-free patients would accept a false-positive rate of less than one per week. Patients with recurring seizures would accept a higher false-positive rate. “Most patients said [that] as long as the ratio of false detections to true detections was not more than 1:1, they would find that acceptable,” said Dr. Krauss.
Patients also want rapid detection of seizures so that they can protect themselves or quickly get help. “The majority of patients would like detection to occur with alerting within one minute” of seizure onset, said Dr. Krauss. Some patients want detection to occur within 30 seconds of seizure onset, and about 14% of patients said that detection within three minutes of onset would be sufficient.
Investigators have pursued various methods for seizure detection. The major methods are physiologic (eg, heart rate, pulse oximetry, and electrodermal activity), motion-related (eg, accelerometers, mattress sensors, EMG, and video motion detection), and responsive testing (eg, testing memory and responsiveness). The best technique may be to combine several of these methods to minimize the rate of false positives, said Dr. Krauss.
SmartWatch
One device that currently is available is SmartWatch, which is manufactured by SmartMonitor. The SmartWatch device is a wrist accelerometer that predominantly detects convulsive seizures. Data from epilepsy monitoring units (EMUs) on the device’s efficacy have been mixed. In a Stanford University study, SmartWatch recorded 62 seizures in 27 patients. Nine patients had 13 tonic–clonic seizures, and the device detected 12 of them. The device had a false positive rate of 87%. In a University of Tennessee study involving 41 patients who had 191 seizures, the SmartWatch device detected 31% of tonic–clonic seizures. These studies suggest that the device has “somewhat limited sensitivity without individualizing settings,” and its accuracy during real-world use is unclear, said Dr. Krauss.
Embrace Watch
The device furthest along in development is Embrace Watch, which is being designed by Empatica. Embrace Watch is a smart watch that performs electrodermal and accelerometer measurements and is connected to a smart phone. It uses an app that graphically displays information about the user’s activity, stress level, and sleep. The watch is intended to detect convulsive seizures and send alerts to caregivers.
One reason that Embrace Watch measures electrodermal activity is that the latter correlates with postictal EEG suppression. Research indicates that postictal generalized EEG suppression corresponds with the risk of SUDEP. “That [finding] raises the possibility that the Empatica device may be useful for intervening in SUDEP,” said Dr. Krauss.
An ongoing study is evaluating Embrace Watch’s efficacy in an EMU. Investigators collected video EEG data for 69 patients and monitored electrodermal activity and movement with the Embrace Watch. The investigators reviewed the detection of 55 convulsive seizures in 22 patients. They tested two classifier models, which were different combinations of electrodermal activity and heart rate changes. One classifier model had 100% sensitivity, but a moderately high rate of false alarms (1.26/day). The other classifier model had a sensitivity of 95% and a rate of 0.2 false alarms per day, which may be acceptable for a patient with uncontrolled seizures, said Dr. Krauss. A separate case study suggests that Embrace Watch accurately detects major seizures in patients with Dravet syndrome.
Brain Sentinel
The FDA is reviewing the Brain Sentinel seizure-monitoring system, which uses EMG recordings to detect convulsive seizures. The device takes advantage of a characteristic firing pattern on EMG that is associated with convulsive seizures. Research has indicated that, when used properly, the system detects seizures with near-perfect accuracy. The system’s accuracy was slightly higher in adults than in a group of adults and children. The average time between seizure onset and alarm was 5.34 seconds in adults and 7.70 seconds in adults and children. The rate of false positives per eight-hour period was 0.51 in adults and 0.48 in adults and children. Most false alarms occurred in a minority of participants. “This device is probably going to be effective for detecting convulsive seizures in patients with uncontrolled epilepsy,” said Dr. Krauss.
EpiWatch App
Dr. Krauss and Nathan Crone, MD, Professor of Neurology at Johns Hopkins University School of Medicine, are developing a seizure-detection app called EpiWatch for use on the Apple Watch. Their objective is to use the Apple Watch’s ability to monitor heart rate, movement, and position to detect seizures. Through the Apple Watch’s user interface, the app asks patients to label seizures and attempts to reduce the number of false detections. During a seizure, the app tests the user’s responsiveness by asking him or her to tap the watch. The test occurs at 20 seconds after seizure onset and at one-minute intervals thereafter. If the user is responsive, the app administers a test of working memory that involves repeating a series of random numbers. At 10 minutes after the seizure ends, the app asks the user whether he or she had had a seizure, whether he or she had had an aura, and whether he or she had lost awareness. These data are logged into a journal that can be transmitted.
Drs. Krauss and Crone are using Apple ResearchKit to study the app’s efficacy. They have enrolled approximately 700 participants in the study, and about 40% of them were able to activate the app during a seizure. The seizure types recorded so far are representative of those of the general US population of patients with epilepsy. Approximately 30% of participants had a 50% increase in heart rate during their seizure. About two-thirds of patients had a 30% increase in heart rate. A significant number of patients with complex partial seizures had decreases in heart rate during their seizure. “Heart rate alone would probably not be a sensitive screening technique for seizures, but it could be one component of an algorithm,” said Dr. Krauss.
Can These Devices Prevent SUDEP?
Many of these devices were designed with the goal of enabling interventions, particularly during severe nocturnal convulsive seizures, to prevent SUDEP. The current understanding of SUDEP provides grounds for optimism that such interventions could be achieved, said Dr. Krauss. Many patients with tonic–clonic seizures have oxygen saturation, postictal generalized EEG suppression, and autonomic alterations. If patients become immobile during a seizure and are lying face down, they may become asphyxiated. “The question is whether we can intervene at that point to prevent the subsequent cardiac arrhythmias which lead to their death,” said Dr. Krauss. A caregiver, for example, could turn a patient on his or her side and stimulate him or her to promote breathing. If the caregiver finds the patient at a later time after seizure onset, he or she could attempt resuscitation. “This is our general concept of perhaps how SUDEP intervention could be performed using mobile device detectors,” Dr. Krauss concluded.
—Erik Greb
Suggested Reading
Hoppe C, Feldmann M, Blachut B, et al. Novel techniques for automated seizure registration: Patients’ wants and needs. Epilepsy Behav. 2015;52(Pt A):1-7.
Lhatoo SD, Nei M, Raghavan M, et al. Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures. Epilepsia. 2016;57(7):1161-1168.
Van de Vel A, Smets K, Wouters K, Ceulemans B. Automated non-EEG based seizure detection: Do users have a say? Epilepsy Behav. 2016;62:121-128.
Velez M, Fisher RS, Bartlett V, Le S. Tracking generalized tonic-clonic seizures with a wrist accelerometer linked to an online database. Seizure. 2016;39:13-18.
HOUSTON—Mobile or wearable devices that observe autonomic and motor changes may provide seizure detection, according to an overview presented at the 70th Annual Meeting of the American Epilepsy Society. Devices that monitor heart rate, electrodermal changes, and electromyogram (EMG) changes also may provide accurate detection of convulsive seizures. Many such devices are in development, and some already are available. They may be convenient for patients to use and could provide opportunities for interventions to prevent sudden unexpected death in epilepsy (SUDEP).
What Do Patients Want?
In 2015, Hoppe and colleagues published the results of their survey of patients’ preferences for automated seizure-detection devices. The authors found that patients want convenient devices such as wearable wristbands, but do not want devices that are conspicuous. Patients want devices that perform automatic seizure registration and make emergency calls to family members or caregivers. They do not, however, want devices that notify their doctors automatically about seizures, preferring to maintain control of their own medical data. On the other hand, patients do want to get help during medical appointments with controlling and using the devices. Finally, patients want devices that predict seizures, but this task “probably requires intracranial recording,” said Gregory Krauss, MD, Professor of Neurology at Johns Hopkins University School of Medicine in Baltimore.
Another survey asked patients about the accuracy that they wanted from these devices. One survey suggested that patients would accept a false-positive or false-negative rate of less than 25%. Seizure-free patients would accept a false-positive rate of less than one per week. Patients with recurring seizures would accept a higher false-positive rate. “Most patients said [that] as long as the ratio of false detections to true detections was not more than 1:1, they would find that acceptable,” said Dr. Krauss.
Patients also want rapid detection of seizures so that they can protect themselves or quickly get help. “The majority of patients would like detection to occur with alerting within one minute” of seizure onset, said Dr. Krauss. Some patients want detection to occur within 30 seconds of seizure onset, and about 14% of patients said that detection within three minutes of onset would be sufficient.
Investigators have pursued various methods for seizure detection. The major methods are physiologic (eg, heart rate, pulse oximetry, and electrodermal activity), motion-related (eg, accelerometers, mattress sensors, EMG, and video motion detection), and responsive testing (eg, testing memory and responsiveness). The best technique may be to combine several of these methods to minimize the rate of false positives, said Dr. Krauss.
SmartWatch
One device that currently is available is SmartWatch, which is manufactured by SmartMonitor. The SmartWatch device is a wrist accelerometer that predominantly detects convulsive seizures. Data from epilepsy monitoring units (EMUs) on the device’s efficacy have been mixed. In a Stanford University study, SmartWatch recorded 62 seizures in 27 patients. Nine patients had 13 tonic–clonic seizures, and the device detected 12 of them. The device had a false positive rate of 87%. In a University of Tennessee study involving 41 patients who had 191 seizures, the SmartWatch device detected 31% of tonic–clonic seizures. These studies suggest that the device has “somewhat limited sensitivity without individualizing settings,” and its accuracy during real-world use is unclear, said Dr. Krauss.
Embrace Watch
The device furthest along in development is Embrace Watch, which is being designed by Empatica. Embrace Watch is a smart watch that performs electrodermal and accelerometer measurements and is connected to a smart phone. It uses an app that graphically displays information about the user’s activity, stress level, and sleep. The watch is intended to detect convulsive seizures and send alerts to caregivers.
One reason that Embrace Watch measures electrodermal activity is that the latter correlates with postictal EEG suppression. Research indicates that postictal generalized EEG suppression corresponds with the risk of SUDEP. “That [finding] raises the possibility that the Empatica device may be useful for intervening in SUDEP,” said Dr. Krauss.
An ongoing study is evaluating Embrace Watch’s efficacy in an EMU. Investigators collected video EEG data for 69 patients and monitored electrodermal activity and movement with the Embrace Watch. The investigators reviewed the detection of 55 convulsive seizures in 22 patients. They tested two classifier models, which were different combinations of electrodermal activity and heart rate changes. One classifier model had 100% sensitivity, but a moderately high rate of false alarms (1.26/day). The other classifier model had a sensitivity of 95% and a rate of 0.2 false alarms per day, which may be acceptable for a patient with uncontrolled seizures, said Dr. Krauss. A separate case study suggests that Embrace Watch accurately detects major seizures in patients with Dravet syndrome.
Brain Sentinel
The FDA is reviewing the Brain Sentinel seizure-monitoring system, which uses EMG recordings to detect convulsive seizures. The device takes advantage of a characteristic firing pattern on EMG that is associated with convulsive seizures. Research has indicated that, when used properly, the system detects seizures with near-perfect accuracy. The system’s accuracy was slightly higher in adults than in a group of adults and children. The average time between seizure onset and alarm was 5.34 seconds in adults and 7.70 seconds in adults and children. The rate of false positives per eight-hour period was 0.51 in adults and 0.48 in adults and children. Most false alarms occurred in a minority of participants. “This device is probably going to be effective for detecting convulsive seizures in patients with uncontrolled epilepsy,” said Dr. Krauss.
EpiWatch App
Dr. Krauss and Nathan Crone, MD, Professor of Neurology at Johns Hopkins University School of Medicine, are developing a seizure-detection app called EpiWatch for use on the Apple Watch. Their objective is to use the Apple Watch’s ability to monitor heart rate, movement, and position to detect seizures. Through the Apple Watch’s user interface, the app asks patients to label seizures and attempts to reduce the number of false detections. During a seizure, the app tests the user’s responsiveness by asking him or her to tap the watch. The test occurs at 20 seconds after seizure onset and at one-minute intervals thereafter. If the user is responsive, the app administers a test of working memory that involves repeating a series of random numbers. At 10 minutes after the seizure ends, the app asks the user whether he or she had had a seizure, whether he or she had had an aura, and whether he or she had lost awareness. These data are logged into a journal that can be transmitted.
Drs. Krauss and Crone are using Apple ResearchKit to study the app’s efficacy. They have enrolled approximately 700 participants in the study, and about 40% of them were able to activate the app during a seizure. The seizure types recorded so far are representative of those of the general US population of patients with epilepsy. Approximately 30% of participants had a 50% increase in heart rate during their seizure. About two-thirds of patients had a 30% increase in heart rate. A significant number of patients with complex partial seizures had decreases in heart rate during their seizure. “Heart rate alone would probably not be a sensitive screening technique for seizures, but it could be one component of an algorithm,” said Dr. Krauss.
Can These Devices Prevent SUDEP?
Many of these devices were designed with the goal of enabling interventions, particularly during severe nocturnal convulsive seizures, to prevent SUDEP. The current understanding of SUDEP provides grounds for optimism that such interventions could be achieved, said Dr. Krauss. Many patients with tonic–clonic seizures have oxygen saturation, postictal generalized EEG suppression, and autonomic alterations. If patients become immobile during a seizure and are lying face down, they may become asphyxiated. “The question is whether we can intervene at that point to prevent the subsequent cardiac arrhythmias which lead to their death,” said Dr. Krauss. A caregiver, for example, could turn a patient on his or her side and stimulate him or her to promote breathing. If the caregiver finds the patient at a later time after seizure onset, he or she could attempt resuscitation. “This is our general concept of perhaps how SUDEP intervention could be performed using mobile device detectors,” Dr. Krauss concluded.
—Erik Greb
Suggested Reading
Hoppe C, Feldmann M, Blachut B, et al. Novel techniques for automated seizure registration: Patients’ wants and needs. Epilepsy Behav. 2015;52(Pt A):1-7.
Lhatoo SD, Nei M, Raghavan M, et al. Nonseizure SUDEP: Sudden unexpected death in epilepsy without preceding epileptic seizures. Epilepsia. 2016;57(7):1161-1168.
Van de Vel A, Smets K, Wouters K, Ceulemans B. Automated non-EEG based seizure detection: Do users have a say? Epilepsy Behav. 2016;62:121-128.
Velez M, Fisher RS, Bartlett V, Le S. Tracking generalized tonic-clonic seizures with a wrist accelerometer linked to an online database. Seizure. 2016;39:13-18.
