Susan London

SEATTLE – Nearly a third of patients who experience a generalized convulsive seizure develop pulmonary edema, suggests a small cohort study reported at the annual meeting of the American Epilepsy Society. The longer the seizure lasts, the higher the probability of this complication.

“There are a few theories about how pulmonary edema can develop” in this context, noted first author Dr. Jeffrey Kennedy of the UC Davis Health System in Sacramento, Calif. Neurogenic mechanisms, hypoxemia, and prolonged negative intrathoracic pressure have all been implicated.

As far as the clinical implications, “postictal pulmonary edema may play a role in the mechanisms of SUDEP (sudden unexpected death in epilepsy),” he proposed at the annual meeting of the American Epilepsy Society.

Session attendee Dr. Kevin Chapman of the child neurology section in the department of pediatrics at Children’s Hospital Colorado, Aurora, asked, “If you identify somebody who has pulmonary edema, what do you do with them?”

“We have been following the patients who are clinically stable,” Dr. Kennedy replied. “We had a patient we identified with Takotsubo cardiomyopathy, which triggered some additional patient care from our cardiology department.”

“I think it just identifies patients who are at higher risk” for poor outcomes, he speculated. “In the EMU [epilepsy monitoring unit], when it comes to letting patients have more seizures, it does make us conservative as far as restarting medications and maybe trying to start giving them some benzodiazepines to try to shut things down.”

Another attendee commented, “Some of my patients’ relatives are very alarmed when the patient suffers severe cyanosis after a seizure. The first thing that our emergency staff will do when they arrive will be to clasp an oxygen mask over them. So our patients ask us, ‘Please, will we provide them with oxygen?’ I have a sneaking suspicion from your data that they may be justified in that. What would you advise?”

Another study done by the UC Davis group looked at a variety of peri-ictal interventions and found simple nursing practices worked about as well as oxygen, according to Dr. Kennedy (Epilepsia 2013;54:377-82). “It seems like just doing something – stimulating the patient, turning them on their side – is enough, rather than just administering oxygen.”

In an interview, session comoderator Dr. Amy Crepeau, a neurologist at the Mayo Clinic Arizona in Phoenix, said the observed incidence of pulmonary edema raises important questions: “Is this something we need to be more conscientious about and really intervene more closely? Should we be shortening the duration of time before we stop seizures and not letting them go as long? It seems as though they have done that at UC Davis – kind of limited the number of seizures that they allow patients to have in the epilepsy monitoring unit.”

“This study comes back to this issue of who’s at risk for SUDEP, what are the causes for SUDEP, and what are the interventions we can use to try to prevent that or lessen the risk for it,” she added. “We are looking forward to seeing whether these patients have any increased risk of SUDEP that associates with the pulmonary edema.”

Dr. Kennedy and colleagues studied 24 consecutive adult patients, mean age 32, who experienced generalized convulsive seizures while undergoing monitoring in the UC Davis EMU, where all patients with such seizures receive a chest x-ray soon afterward as a safety measure.

Overall, 29% of the patients were found to have pulmonary edema, with or without focal infiltrates, on their chest x-ray, and another 17% were found to have focal infiltrates only.

The mean time elapsed between the seizure and the chest x-ray acquisition was 225 minutes in the patients with abnormal findings and 196 minutes in the patients with normal findings, a nonsignificant difference, reported Dr. Kennedy, who disclosed that he had no relevant conflicts of interest.

The seizure duration was more than twice as long among patients with chest x-ray abnormalities as among counterparts without these abnormalities (250 vs. 101 seconds; P = .002), and the probability of abnormalities increased with seizure duration.

The groups with and without chest x-rays abnormalities did not differ significantly with respect to a variety of demographic and cardiorespiratory and other clinical factors, however.

SEATTLE – Nearly a third of patients who experience a generalized convulsive seizure develop pulmonary edema, suggests a small cohort study reported at the annual meeting of the American Epilepsy Society. The longer the seizure lasts, the higher the probability of this complication.

“There are a few theories about how pulmonary edema can develop” in this context, noted first author Dr. Jeffrey Kennedy of the UC Davis Health System in Sacramento, Calif. Neurogenic mechanisms, hypoxemia, and prolonged negative intrathoracic pressure have all been implicated.

As far as the clinical implications, “postictal pulmonary edema may play a role in the mechanisms of SUDEP (sudden unexpected death in epilepsy),” he proposed at the annual meeting of the American Epilepsy Society.

Session attendee Dr. Kevin Chapman of the child neurology section in the department of pediatrics at Children’s Hospital Colorado, Aurora, asked, “If you identify somebody who has pulmonary edema, what do you do with them?”

“We have been following the patients who are clinically stable,” Dr. Kennedy replied. “We had a patient we identified with Takotsubo cardiomyopathy, which triggered some additional patient care from our cardiology department.”

“I think it just identifies patients who are at higher risk” for poor outcomes, he speculated. “In the EMU [epilepsy monitoring unit], when it comes to letting patients have more seizures, it does make us conservative as far as restarting medications and maybe trying to start giving them some benzodiazepines to try to shut things down.”

Another attendee commented, “Some of my patients’ relatives are very alarmed when the patient suffers severe cyanosis after a seizure. The first thing that our emergency staff will do when they arrive will be to clasp an oxygen mask over them. So our patients ask us, ‘Please, will we provide them with oxygen?’ I have a sneaking suspicion from your data that they may be justified in that. What would you advise?”

Another study done by the UC Davis group looked at a variety of peri-ictal interventions and found simple nursing practices worked about as well as oxygen, according to Dr. Kennedy (Epilepsia 2013;54:377-82). “It seems like just doing something – stimulating the patient, turning them on their side – is enough, rather than just administering oxygen.”

In an interview, session comoderator Dr. Amy Crepeau, a neurologist at the Mayo Clinic Arizona in Phoenix, said the observed incidence of pulmonary edema raises important questions: “Is this something we need to be more conscientious about and really intervene more closely? Should we be shortening the duration of time before we stop seizures and not letting them go as long? It seems as though they have done that at UC Davis – kind of limited the number of seizures that they allow patients to have in the epilepsy monitoring unit.”

“This study comes back to this issue of who’s at risk for SUDEP, what are the causes for SUDEP, and what are the interventions we can use to try to prevent that or lessen the risk for it,” she added. “We are looking forward to seeing whether these patients have any increased risk of SUDEP that associates with the pulmonary edema.”

Dr. Kennedy and colleagues studied 24 consecutive adult patients, mean age 32, who experienced generalized convulsive seizures while undergoing monitoring in the UC Davis EMU, where all patients with such seizures receive a chest x-ray soon afterward as a safety measure.

Overall, 29% of the patients were found to have pulmonary edema, with or without focal infiltrates, on their chest x-ray, and another 17% were found to have focal infiltrates only.

The mean time elapsed between the seizure and the chest x-ray acquisition was 225 minutes in the patients with abnormal findings and 196 minutes in the patients with normal findings, a nonsignificant difference, reported Dr. Kennedy, who disclosed that he had no relevant conflicts of interest.

The seizure duration was more than twice as long among patients with chest x-ray abnormalities as among counterparts without these abnormalities (250 vs. 101 seconds; P = .002), and the probability of abnormalities increased with seizure duration.

The groups with and without chest x-rays abnormalities did not differ significantly with respect to a variety of demographic and cardiorespiratory and other clinical factors, however.

SEATTLE – Nearly a third of patients who experience a generalized convulsive seizure develop pulmonary edema, suggests a small cohort study reported at the annual meeting of the American Epilepsy Society. The longer the seizure lasts, the higher the probability of this complication.

“There are a few theories about how pulmonary edema can develop” in this context, noted first author Dr. Jeffrey Kennedy of the UC Davis Health System in Sacramento, Calif. Neurogenic mechanisms, hypoxemia, and prolonged negative intrathoracic pressure have all been implicated.

As far as the clinical implications, “postictal pulmonary edema may play a role in the mechanisms of SUDEP (sudden unexpected death in epilepsy),” he proposed at the annual meeting of the American Epilepsy Society.

Session attendee Dr. Kevin Chapman of the child neurology section in the department of pediatrics at Children’s Hospital Colorado, Aurora, asked, “If you identify somebody who has pulmonary edema, what do you do with them?”

“We have been following the patients who are clinically stable,” Dr. Kennedy replied. “We had a patient we identified with Takotsubo cardiomyopathy, which triggered some additional patient care from our cardiology department.”

“I think it just identifies patients who are at higher risk” for poor outcomes, he speculated. “In the EMU [epilepsy monitoring unit], when it comes to letting patients have more seizures, it does make us conservative as far as restarting medications and maybe trying to start giving them some benzodiazepines to try to shut things down.”

Another attendee commented, “Some of my patients’ relatives are very alarmed when the patient suffers severe cyanosis after a seizure. The first thing that our emergency staff will do when they arrive will be to clasp an oxygen mask over them. So our patients ask us, ‘Please, will we provide them with oxygen?’ I have a sneaking suspicion from your data that they may be justified in that. What would you advise?”

Another study done by the UC Davis group looked at a variety of peri-ictal interventions and found simple nursing practices worked about as well as oxygen, according to Dr. Kennedy (Epilepsia 2013;54:377-82). “It seems like just doing something – stimulating the patient, turning them on their side – is enough, rather than just administering oxygen.”

In an interview, session comoderator Dr. Amy Crepeau, a neurologist at the Mayo Clinic Arizona in Phoenix, said the observed incidence of pulmonary edema raises important questions: “Is this something we need to be more conscientious about and really intervene more closely? Should we be shortening the duration of time before we stop seizures and not letting them go as long? It seems as though they have done that at UC Davis – kind of limited the number of seizures that they allow patients to have in the epilepsy monitoring unit.”

“This study comes back to this issue of who’s at risk for SUDEP, what are the causes for SUDEP, and what are the interventions we can use to try to prevent that or lessen the risk for it,” she added. “We are looking forward to seeing whether these patients have any increased risk of SUDEP that associates with the pulmonary edema.”

Dr. Kennedy and colleagues studied 24 consecutive adult patients, mean age 32, who experienced generalized convulsive seizures while undergoing monitoring in the UC Davis EMU, where all patients with such seizures receive a chest x-ray soon afterward as a safety measure.

Overall, 29% of the patients were found to have pulmonary edema, with or without focal infiltrates, on their chest x-ray, and another 17% were found to have focal infiltrates only.

The mean time elapsed between the seizure and the chest x-ray acquisition was 225 minutes in the patients with abnormal findings and 196 minutes in the patients with normal findings, a nonsignificant difference, reported Dr. Kennedy, who disclosed that he had no relevant conflicts of interest.

The seizure duration was more than twice as long among patients with chest x-ray abnormalities as among counterparts without these abnormalities (250 vs. 101 seconds; P = .002), and the probability of abnormalities increased with seizure duration.

The groups with and without chest x-rays abnormalities did not differ significantly with respect to a variety of demographic and cardiorespiratory and other clinical factors, however.

SEATTLE– Most pediatric patients with intractable epilepsy fare similarly well if they follow the less-restrictive modified Atkins diet instead of the classic ketogenic diet, new data suggest. The former may be better in patients with kidney disease, whereas the latter may be better for very young children.

“The modified Atkins diet is much easier to follow, and many physicians think that it shows much lower [rates of] complications. But until now, there have been very few studies comparing the ketogenic diet and modified Atkins diet,” lead investigator Dr. Jeong-A Kim commented in an interview at the annual meeting of the American Epilepsy Society, where she presented the findings.

The investigators conducted a randomized trial pitting the two diets against each other among 104 patients aged 1-18 years who had drug-refractory epilepsy and had never received dietary therapy.

The proportion of patients free of seizures, defined as having none for at least the past month, did not differ significantly overall between the ketogenic diet and modified Atkins diet groups at 3 months (32.7% vs. 26.4%) or at 6 months (29.4% vs. 20.7%), according to results reported in a poster session. There was also no significant difference in the proportions achieving a greater than 50% reduction and a greater than 90% reduction in seizures.

In stratified analyses, the findings were similar for most age groups, except for children 1 or 2 years old, who had a significantly higher rate of freedom from seizures at 3 months if they were on the ketogenic diet (17.6% vs. 7.5%; P = .047).

The diets were statistically indistinguishable with respect to rates of most adverse effects, but hypercalciuria was twice as common with the ketogenic diet (35.3% vs. 13.2%; P = .01). Also, a larger share of patients in the ketogenic diet group stopped their diet because of adverse effects.

“I usually first try the ketogenic diet, but if the patients show some side effects such as hypercalciuria or GI trouble, something like that, then I usually change it to the modified Atkins diet,” commented Dr. Kim, who is a pediatric neurologist at Severance Children’s Hospital, Yonsei University Health System, in Seoul, South Korea.

Clinicians should know “You have choices when you think about dietary therapy: It’s not just the ketogenic diet, you also have choices such as the modified Atkins diet,” she maintained. “So if a patient has kidney problems or some other problems, then you can try the modified Atkins diet instead of the ketogenic diet. You don’t have to have prejudices or misconceptions about dietary therapy; you also have other options for dietary therapy.”

“For younger patients who have Lennox-Gastaut syndrome or infantile spasms, it would be better to try the ketogenic diet first,” advised Dr. Kim, who disclosed that she had no relevant conflicts of interest.

SEATTLE– Most pediatric patients with intractable epilepsy fare similarly well if they follow the less-restrictive modified Atkins diet instead of the classic ketogenic diet, new data suggest. The former may be better in patients with kidney disease, whereas the latter may be better for very young children.

“The modified Atkins diet is much easier to follow, and many physicians think that it shows much lower [rates of] complications. But until now, there have been very few studies comparing the ketogenic diet and modified Atkins diet,” lead investigator Dr. Jeong-A Kim commented in an interview at the annual meeting of the American Epilepsy Society, where she presented the findings.

The investigators conducted a randomized trial pitting the two diets against each other among 104 patients aged 1-18 years who had drug-refractory epilepsy and had never received dietary therapy.

The proportion of patients free of seizures, defined as having none for at least the past month, did not differ significantly overall between the ketogenic diet and modified Atkins diet groups at 3 months (32.7% vs. 26.4%) or at 6 months (29.4% vs. 20.7%), according to results reported in a poster session. There was also no significant difference in the proportions achieving a greater than 50% reduction and a greater than 90% reduction in seizures.

In stratified analyses, the findings were similar for most age groups, except for children 1 or 2 years old, who had a significantly higher rate of freedom from seizures at 3 months if they were on the ketogenic diet (17.6% vs. 7.5%; P = .047).

The diets were statistically indistinguishable with respect to rates of most adverse effects, but hypercalciuria was twice as common with the ketogenic diet (35.3% vs. 13.2%; P = .01). Also, a larger share of patients in the ketogenic diet group stopped their diet because of adverse effects.

“I usually first try the ketogenic diet, but if the patients show some side effects such as hypercalciuria or GI trouble, something like that, then I usually change it to the modified Atkins diet,” commented Dr. Kim, who is a pediatric neurologist at Severance Children’s Hospital, Yonsei University Health System, in Seoul, South Korea.

Clinicians should know “You have choices when you think about dietary therapy: It’s not just the ketogenic diet, you also have choices such as the modified Atkins diet,” she maintained. “So if a patient has kidney problems or some other problems, then you can try the modified Atkins diet instead of the ketogenic diet. You don’t have to have prejudices or misconceptions about dietary therapy; you also have other options for dietary therapy.”

“For younger patients who have Lennox-Gastaut syndrome or infantile spasms, it would be better to try the ketogenic diet first,” advised Dr. Kim, who disclosed that she had no relevant conflicts of interest.

SEATTLE– Most pediatric patients with intractable epilepsy fare similarly well if they follow the less-restrictive modified Atkins diet instead of the classic ketogenic diet, new data suggest. The former may be better in patients with kidney disease, whereas the latter may be better for very young children.

“The modified Atkins diet is much easier to follow, and many physicians think that it shows much lower [rates of] complications. But until now, there have been very few studies comparing the ketogenic diet and modified Atkins diet,” lead investigator Dr. Jeong-A Kim commented in an interview at the annual meeting of the American Epilepsy Society, where she presented the findings.

The investigators conducted a randomized trial pitting the two diets against each other among 104 patients aged 1-18 years who had drug-refractory epilepsy and had never received dietary therapy.

The proportion of patients free of seizures, defined as having none for at least the past month, did not differ significantly overall between the ketogenic diet and modified Atkins diet groups at 3 months (32.7% vs. 26.4%) or at 6 months (29.4% vs. 20.7%), according to results reported in a poster session. There was also no significant difference in the proportions achieving a greater than 50% reduction and a greater than 90% reduction in seizures.

In stratified analyses, the findings were similar for most age groups, except for children 1 or 2 years old, who had a significantly higher rate of freedom from seizures at 3 months if they were on the ketogenic diet (17.6% vs. 7.5%; P = .047).

The diets were statistically indistinguishable with respect to rates of most adverse effects, but hypercalciuria was twice as common with the ketogenic diet (35.3% vs. 13.2%; P = .01). Also, a larger share of patients in the ketogenic diet group stopped their diet because of adverse effects.

“I usually first try the ketogenic diet, but if the patients show some side effects such as hypercalciuria or GI trouble, something like that, then I usually change it to the modified Atkins diet,” commented Dr. Kim, who is a pediatric neurologist at Severance Children’s Hospital, Yonsei University Health System, in Seoul, South Korea.

Clinicians should know “You have choices when you think about dietary therapy: It’s not just the ketogenic diet, you also have choices such as the modified Atkins diet,” she maintained. “So if a patient has kidney problems or some other problems, then you can try the modified Atkins diet instead of the ketogenic diet. You don’t have to have prejudices or misconceptions about dietary therapy; you also have other options for dietary therapy.”

“For younger patients who have Lennox-Gastaut syndrome or infantile spasms, it would be better to try the ketogenic diet first,” advised Dr. Kim, who disclosed that she had no relevant conflicts of interest.

SEATTLE – Different generic versions of lamotrigine had essentially the same pharmacokinetics, safety, and efficacy in controlling seizures in a randomized, head-to-head cross-over trial reported at the annual meeting of the American Epilepsy Society.

“There is all this worry about generics, even though the FDA [Food and Drug Administration] says, ‘We do rigorous testing, and these generics are beautiful, and you don’t have to worry, and you don’t have to measure blood levels of anything,’” lead investigator Dr. Michael D. Privitera commented in an interview. And pharmacies often switch patients with epilepsy between generic antiepileptic drug products with little or no notice.

“What we tried to do here was sort of a worst-case scenario [comparison] with two different generics that would be the most different, and we demonstrated that they were extremely close,” he said. “Although there are other studies that you need to look at too, from this study, I would say that the risks of switching from generic to generic are probably less than one might anticipate from reading the nonrigorous studies that are out there in the literature.”

To capture real-world conditions, Dr. Privitera and his colleagues of the EQUIGEN (Equivalence Among Generic AEDs) study group designed a practical trial using repeated dosing among epilepsy patients who could be taking other medications. “The FDA does all their studies in normal volunteers using single doses, never people with epilepsy, never somebody taking a drug,” he noted.

In the study, the investigators chose for comparison the two generic lamotrigine products on the market having the most disparate dissolution and content characteristics based on testing, and the most disparate pharmacokinetic profiles based on data submitted to the FDA by the manufacturers for approval. For the latter, the products had the lowest and highest values for the total drug exposure as assessed from the area under the curve (AUC) and for the peak blood concentration (Cmax) that still fell within the permitted 90% confidence interval of 80% to 120% relative to the brand-name drug.

Study participants were 35 adults with epilepsy, with or without comorbidities, who were receiving lamotrigine in a dose that was a multiple of 100 mg, with equal morning and evening doses, as either monotherapy or polytherapy. The sample was enriched in that five of the patients reported experiencing troubles when switching between generics in the past.

“In general, these were not people with high seizure frequency because we really wanted them to be stable and compliant, because compliance is the single most important thing in getting these kinds of numbers,” noted Dr. Privitera, professor of neurology at the University of Cincinnati and director of the Epilepsy Center at the University of Cincinnati Neuroscience Institute.

After randomization to the order of products, patients took the low and high generic products on a blinded basis for four alternating 2-week periods. Compliance was assessed with tablet counts, patient diaries, and computerized compliance caps on bottles. Pharmacokinetics were assessed in each period with serial blood measurements.

Results presented in a poster session showed that none of the patients experienced adverse events or lost seizure control, as assessed from self-reported seizure frequency, when switching between the two generic products, reported Dr. Privitera, who disclosed that he had no relevant conflicts of interest.

Additionally, the two products did not differ significantly in pharmacokinetics, meeting the FDA standards for bioequivalence for both the ratio of their AUC values (90% confidence interval, 98%-103%) and the ratio of their Cmax values (90% confidence interval, 99%-105%). “We didn’t find any outlier group here,” he added.

Findings were essentially the same after controlling for concomitant use of enzyme-inducing antiepileptic drugs, sex, dose, and missing data.

Dr. Privitera speculated that reported difficulties after switches of generic antiepileptic drugs have been because of compliance issues and not the drug products. That is, the differing appearance of various generics may confuse patients, causing them to stop taking the medication, as suggested by recent research (JAMA Intern. Med. 2013;173:202-8), or to take too much.

“The FDA actually wants generic drugs [from different manufacturers] to look different,” he noted. But there has recently been a push from clinicians “to say look, if you are making generic lamotrigine, no matter who manufactures it, it should all look the same, and then people won’t get confused when they go from a blue triangle to a white round to a yellow round.”

The investigators are conducting a similar trial that is comparing brand name drug lamotrigine (Lamictal) with generic versions in patients with epilepsy, but using single doses.

SEATTLE – Different generic versions of lamotrigine had essentially the same pharmacokinetics, safety, and efficacy in controlling seizures in a randomized, head-to-head cross-over trial reported at the annual meeting of the American Epilepsy Society.

“There is all this worry about generics, even though the FDA [Food and Drug Administration] says, ‘We do rigorous testing, and these generics are beautiful, and you don’t have to worry, and you don’t have to measure blood levels of anything,’” lead investigator Dr. Michael D. Privitera commented in an interview. And pharmacies often switch patients with epilepsy between generic antiepileptic drug products with little or no notice.

“What we tried to do here was sort of a worst-case scenario [comparison] with two different generics that would be the most different, and we demonstrated that they were extremely close,” he said. “Although there are other studies that you need to look at too, from this study, I would say that the risks of switching from generic to generic are probably less than one might anticipate from reading the nonrigorous studies that are out there in the literature.”

To capture real-world conditions, Dr. Privitera and his colleagues of the EQUIGEN (Equivalence Among Generic AEDs) study group designed a practical trial using repeated dosing among epilepsy patients who could be taking other medications. “The FDA does all their studies in normal volunteers using single doses, never people with epilepsy, never somebody taking a drug,” he noted.

In the study, the investigators chose for comparison the two generic lamotrigine products on the market having the most disparate dissolution and content characteristics based on testing, and the most disparate pharmacokinetic profiles based on data submitted to the FDA by the manufacturers for approval. For the latter, the products had the lowest and highest values for the total drug exposure as assessed from the area under the curve (AUC) and for the peak blood concentration (Cmax) that still fell within the permitted 90% confidence interval of 80% to 120% relative to the brand-name drug.

Study participants were 35 adults with epilepsy, with or without comorbidities, who were receiving lamotrigine in a dose that was a multiple of 100 mg, with equal morning and evening doses, as either monotherapy or polytherapy. The sample was enriched in that five of the patients reported experiencing troubles when switching between generics in the past.

“In general, these were not people with high seizure frequency because we really wanted them to be stable and compliant, because compliance is the single most important thing in getting these kinds of numbers,” noted Dr. Privitera, professor of neurology at the University of Cincinnati and director of the Epilepsy Center at the University of Cincinnati Neuroscience Institute.

After randomization to the order of products, patients took the low and high generic products on a blinded basis for four alternating 2-week periods. Compliance was assessed with tablet counts, patient diaries, and computerized compliance caps on bottles. Pharmacokinetics were assessed in each period with serial blood measurements.

Results presented in a poster session showed that none of the patients experienced adverse events or lost seizure control, as assessed from self-reported seizure frequency, when switching between the two generic products, reported Dr. Privitera, who disclosed that he had no relevant conflicts of interest.

Additionally, the two products did not differ significantly in pharmacokinetics, meeting the FDA standards for bioequivalence for both the ratio of their AUC values (90% confidence interval, 98%-103%) and the ratio of their Cmax values (90% confidence interval, 99%-105%). “We didn’t find any outlier group here,” he added.

Findings were essentially the same after controlling for concomitant use of enzyme-inducing antiepileptic drugs, sex, dose, and missing data.

Dr. Privitera speculated that reported difficulties after switches of generic antiepileptic drugs have been because of compliance issues and not the drug products. That is, the differing appearance of various generics may confuse patients, causing them to stop taking the medication, as suggested by recent research (JAMA Intern. Med. 2013;173:202-8), or to take too much.

“The FDA actually wants generic drugs [from different manufacturers] to look different,” he noted. But there has recently been a push from clinicians “to say look, if you are making generic lamotrigine, no matter who manufactures it, it should all look the same, and then people won’t get confused when they go from a blue triangle to a white round to a yellow round.”

The investigators are conducting a similar trial that is comparing brand name drug lamotrigine (Lamictal) with generic versions in patients with epilepsy, but using single doses.

SEATTLE – Different generic versions of lamotrigine had essentially the same pharmacokinetics, safety, and efficacy in controlling seizures in a randomized, head-to-head cross-over trial reported at the annual meeting of the American Epilepsy Society.

“There is all this worry about generics, even though the FDA [Food and Drug Administration] says, ‘We do rigorous testing, and these generics are beautiful, and you don’t have to worry, and you don’t have to measure blood levels of anything,’” lead investigator Dr. Michael D. Privitera commented in an interview. And pharmacies often switch patients with epilepsy between generic antiepileptic drug products with little or no notice.

“What we tried to do here was sort of a worst-case scenario [comparison] with two different generics that would be the most different, and we demonstrated that they were extremely close,” he said. “Although there are other studies that you need to look at too, from this study, I would say that the risks of switching from generic to generic are probably less than one might anticipate from reading the nonrigorous studies that are out there in the literature.”

To capture real-world conditions, Dr. Privitera and his colleagues of the EQUIGEN (Equivalence Among Generic AEDs) study group designed a practical trial using repeated dosing among epilepsy patients who could be taking other medications. “The FDA does all their studies in normal volunteers using single doses, never people with epilepsy, never somebody taking a drug,” he noted.

In the study, the investigators chose for comparison the two generic lamotrigine products on the market having the most disparate dissolution and content characteristics based on testing, and the most disparate pharmacokinetic profiles based on data submitted to the FDA by the manufacturers for approval. For the latter, the products had the lowest and highest values for the total drug exposure as assessed from the area under the curve (AUC) and for the peak blood concentration (Cmax) that still fell within the permitted 90% confidence interval of 80% to 120% relative to the brand-name drug.

Study participants were 35 adults with epilepsy, with or without comorbidities, who were receiving lamotrigine in a dose that was a multiple of 100 mg, with equal morning and evening doses, as either monotherapy or polytherapy. The sample was enriched in that five of the patients reported experiencing troubles when switching between generics in the past.

“In general, these were not people with high seizure frequency because we really wanted them to be stable and compliant, because compliance is the single most important thing in getting these kinds of numbers,” noted Dr. Privitera, professor of neurology at the University of Cincinnati and director of the Epilepsy Center at the University of Cincinnati Neuroscience Institute.

After randomization to the order of products, patients took the low and high generic products on a blinded basis for four alternating 2-week periods. Compliance was assessed with tablet counts, patient diaries, and computerized compliance caps on bottles. Pharmacokinetics were assessed in each period with serial blood measurements.

Results presented in a poster session showed that none of the patients experienced adverse events or lost seizure control, as assessed from self-reported seizure frequency, when switching between the two generic products, reported Dr. Privitera, who disclosed that he had no relevant conflicts of interest.

Additionally, the two products did not differ significantly in pharmacokinetics, meeting the FDA standards for bioequivalence for both the ratio of their AUC values (90% confidence interval, 98%-103%) and the ratio of their Cmax values (90% confidence interval, 99%-105%). “We didn’t find any outlier group here,” he added.

Findings were essentially the same after controlling for concomitant use of enzyme-inducing antiepileptic drugs, sex, dose, and missing data.

Dr. Privitera speculated that reported difficulties after switches of generic antiepileptic drugs have been because of compliance issues and not the drug products. That is, the differing appearance of various generics may confuse patients, causing them to stop taking the medication, as suggested by recent research (JAMA Intern. Med. 2013;173:202-8), or to take too much.

“The FDA actually wants generic drugs [from different manufacturers] to look different,” he noted. But there has recently been a push from clinicians “to say look, if you are making generic lamotrigine, no matter who manufactures it, it should all look the same, and then people won’t get confused when they go from a blue triangle to a white round to a yellow round.”

The investigators are conducting a similar trial that is comparing brand name drug lamotrigine (Lamictal) with generic versions in patients with epilepsy, but using single doses.

VANCOUVER, B.C. – The incidence of unsuspected uterine sarcoma found during surgery for other conditions is low, according to three cohort studies reported at the meeting, sponsored by AAGL.

In one study, researchers at Mount Sinai Hospital in New York City retrospectively studied 815 consecutive women who underwent laparoscopic supracervical hysterectomy or laparoscopic myomectomy with power morcellation at the hospital between 2006 and 2013.

Pathology of the morcellated uteri identified endometrial carcinoma in two patients (one with prolapse and one with a presumed prolapsing fibroid), for an incidence of 0.25%, according to Dr. Charles J. Ascher-Walsh, associate professor of obstetrics, gynecology, and reproductive science at Mount Sinai, and lead author of the study.

None of the patients were found to have a uterine sarcoma or any other cancer.

“There’s obviously very little data sort of looking forward on the risk of morcellating endometrial cancers. It doesn’t seem so far to significantly worsen the prognosis in these patients. There have been a few reviews looking at a cost-effectiveness analysis in biopsying postmenopausal asymptomatic patients who are having prolapse surgery, and so far the conclusions in both of those studies have shown that it’s not cost-effective to biopsy these patients,” Dr. Ascher-Walsh said. “Now I know there are institutions that are biopsying them anyway, and certainly as part of the revamp of people’s protocols with the morcellation debate, I think more institutions are starting to automatically biopsy every patient before morcellation.”

Total laparoscopic hysterectomies were not included in the study, because Dr. Ascher-Walsh usually performs that operation by vaginal approach, he said. “I wanted to focus just on the intra-abdominal morcellation technique. But obviously, in the debate, whether you cut into it vaginally or cut into it with an open myomectomy, you can potentially have the same concerns and risks.”

Mount Sinai has modified its policy on performing morcellation, somewhat, as a result of the ongoing debate, Dr. Ascher-Walsh said.

“We continue to do morcellation, but before doing morcellation, if we don’t have documentation of a typically growing fibroid, or if somebody presents with a large fibroid without any evidence of slow growth over time, we will get an MRI, although the evidence isn’t supportive of MRIs being diagnostic, other than the one study that combined it with [lactate dehydrogenase],” he said.

In the second study, a team led by Dr. Nichole Mahnert, a fellow in obstetrics and gynecology at the University of Michigan, Ann Arbor, used the Michigan Surgical Quality Collaborative database to prospectively study 6,360 women who underwent hysterectomy for a benign indication during 2013.

Pathology identified unexpected uterine sarcoma in 0.22% of patients (1 in 454) overall, and in 0.27% of patients (1 in 370) whose indication for surgery was specifically fibroids. These values are generally on par with the 0.28% of women operated on for fibroids (1 in 352) seen in the Food and Drug Administration assessment, she said.

In the cohort overall, prior venous thromboembolism and preoperative blood transfusion tended to be more common among patients later found to have uterine sarcoma.

Other cancers identified in the entire cohort included endometrial cancer (1.02%), ovarian cancer (1.06%), cervical cancer (0.17%), and metastatic cancer (0.20%).

“Comprehensive preoperative surgical counseling is paramount, and it should include not only the usual risks of surgery, but also the risk of unexpected malignancy and the risk of inadvertent morcellation of an unexpected malignancy. One should also consider the risks and benefits of a laparoscopic versus and open procedure,” Dr. Mahnert recommended. “And until we can more reliably risk-stratify patients to identify those with unexpected uterine sarcomas, we need to support technologies to limit the dissemination of specimens during minimally invasive procedures.”

In the third study, Dr. Katherine A. Hartzell, an ob.gyn. at Kaiser Permanente in San Diego, and her colleagues retrospectively reviewed the charts of all 3,523 women undergoing laparoscopic hysterectomy at the institution between 2001 and 2012.

Of the 941 cases in which power morcellation was used, uterine sarcoma was found in 6 cases or 0.6%; half were endometrial stromal sarcoma and half were leiomyosarcoma. Five of these patients had no evidence of disease after at least 31 months of follow-up. The sixth patient, who had high-grade leiomyosarcoma, died from her disease 3 years after diagnosis.

The uterine sarcoma rate of 0.6% was roughly double the 0.28% estimated by the FDA, Dr. Hartzell noted.

“This higher incidence was probably due to the inclusion of three patients with a delayed presentation of uterine sarcoma when initial pathology was benign,” she said. “These patients were likely discovered because of the captive nature of the Kaiser health care system.”

None of a wide variety of factors evaluated predicted the risk of uterine sarcoma in these patients undergoing morcellation, Dr. Hartzell said.

Among the 2,582 women who did not undergo power morcellation, uterine sarcoma was identified in 5 patients, or 0.2%. Four were alive without evidence of disease after at least 37 months of follow-up. The fifth patient, who had high-grade leiomyosarcoma, died from her disease 2 years after diagnosis.

“The patient about to undergo a minimally invasive procedure with possible power morcellation should be counseled about the possible consequences of morcellation of an undiagnosed malignancy. Alternatives such as mini-laparotomy or an open procedure should be offered. At our institution, we are also now performing morcellation within a tissue containment bag,” she said.

“Given the well-known advantages of laparoscopic surgery and the rarity of uterine sarcomas, it is our opinion that the risk of morcellation of occult malignancy is insufficient to abandon power morcellation,” Dr. Hartzell added.

The researchers reported that they had no relevant conflicts of interest.

VANCOUVER, B.C. – The incidence of unsuspected uterine sarcoma found during surgery for other conditions is low, according to three cohort studies reported at the meeting, sponsored by AAGL.

In one study, researchers at Mount Sinai Hospital in New York City retrospectively studied 815 consecutive women who underwent laparoscopic supracervical hysterectomy or laparoscopic myomectomy with power morcellation at the hospital between 2006 and 2013.

Pathology of the morcellated uteri identified endometrial carcinoma in two patients (one with prolapse and one with a presumed prolapsing fibroid), for an incidence of 0.25%, according to Dr. Charles J. Ascher-Walsh, associate professor of obstetrics, gynecology, and reproductive science at Mount Sinai, and lead author of the study.

None of the patients were found to have a uterine sarcoma or any other cancer.

“There’s obviously very little data sort of looking forward on the risk of morcellating endometrial cancers. It doesn’t seem so far to significantly worsen the prognosis in these patients. There have been a few reviews looking at a cost-effectiveness analysis in biopsying postmenopausal asymptomatic patients who are having prolapse surgery, and so far the conclusions in both of those studies have shown that it’s not cost-effective to biopsy these patients,” Dr. Ascher-Walsh said. “Now I know there are institutions that are biopsying them anyway, and certainly as part of the revamp of people’s protocols with the morcellation debate, I think more institutions are starting to automatically biopsy every patient before morcellation.”

Total laparoscopic hysterectomies were not included in the study, because Dr. Ascher-Walsh usually performs that operation by vaginal approach, he said. “I wanted to focus just on the intra-abdominal morcellation technique. But obviously, in the debate, whether you cut into it vaginally or cut into it with an open myomectomy, you can potentially have the same concerns and risks.”

Mount Sinai has modified its policy on performing morcellation, somewhat, as a result of the ongoing debate, Dr. Ascher-Walsh said.

“We continue to do morcellation, but before doing morcellation, if we don’t have documentation of a typically growing fibroid, or if somebody presents with a large fibroid without any evidence of slow growth over time, we will get an MRI, although the evidence isn’t supportive of MRIs being diagnostic, other than the one study that combined it with [lactate dehydrogenase],” he said.

In the second study, a team led by Dr. Nichole Mahnert, a fellow in obstetrics and gynecology at the University of Michigan, Ann Arbor, used the Michigan Surgical Quality Collaborative database to prospectively study 6,360 women who underwent hysterectomy for a benign indication during 2013.

Pathology identified unexpected uterine sarcoma in 0.22% of patients (1 in 454) overall, and in 0.27% of patients (1 in 370) whose indication for surgery was specifically fibroids. These values are generally on par with the 0.28% of women operated on for fibroids (1 in 352) seen in the Food and Drug Administration assessment, she said.

In the cohort overall, prior venous thromboembolism and preoperative blood transfusion tended to be more common among patients later found to have uterine sarcoma.

Other cancers identified in the entire cohort included endometrial cancer (1.02%), ovarian cancer (1.06%), cervical cancer (0.17%), and metastatic cancer (0.20%).

“Comprehensive preoperative surgical counseling is paramount, and it should include not only the usual risks of surgery, but also the risk of unexpected malignancy and the risk of inadvertent morcellation of an unexpected malignancy. One should also consider the risks and benefits of a laparoscopic versus and open procedure,” Dr. Mahnert recommended. “And until we can more reliably risk-stratify patients to identify those with unexpected uterine sarcomas, we need to support technologies to limit the dissemination of specimens during minimally invasive procedures.”

In the third study, Dr. Katherine A. Hartzell, an ob.gyn. at Kaiser Permanente in San Diego, and her colleagues retrospectively reviewed the charts of all 3,523 women undergoing laparoscopic hysterectomy at the institution between 2001 and 2012.

Of the 941 cases in which power morcellation was used, uterine sarcoma was found in 6 cases or 0.6%; half were endometrial stromal sarcoma and half were leiomyosarcoma. Five of these patients had no evidence of disease after at least 31 months of follow-up. The sixth patient, who had high-grade leiomyosarcoma, died from her disease 3 years after diagnosis.

The uterine sarcoma rate of 0.6% was roughly double the 0.28% estimated by the FDA, Dr. Hartzell noted.

“This higher incidence was probably due to the inclusion of three patients with a delayed presentation of uterine sarcoma when initial pathology was benign,” she said. “These patients were likely discovered because of the captive nature of the Kaiser health care system.”

None of a wide variety of factors evaluated predicted the risk of uterine sarcoma in these patients undergoing morcellation, Dr. Hartzell said.

Among the 2,582 women who did not undergo power morcellation, uterine sarcoma was identified in 5 patients, or 0.2%. Four were alive without evidence of disease after at least 37 months of follow-up. The fifth patient, who had high-grade leiomyosarcoma, died from her disease 2 years after diagnosis.

“The patient about to undergo a minimally invasive procedure with possible power morcellation should be counseled about the possible consequences of morcellation of an undiagnosed malignancy. Alternatives such as mini-laparotomy or an open procedure should be offered. At our institution, we are also now performing morcellation within a tissue containment bag,” she said.

“Given the well-known advantages of laparoscopic surgery and the rarity of uterine sarcomas, it is our opinion that the risk of morcellation of occult malignancy is insufficient to abandon power morcellation,” Dr. Hartzell added.

The researchers reported that they had no relevant conflicts of interest.

VANCOUVER, B.C. – The incidence of unsuspected uterine sarcoma found during surgery for other conditions is low, according to three cohort studies reported at the meeting, sponsored by AAGL.

In one study, researchers at Mount Sinai Hospital in New York City retrospectively studied 815 consecutive women who underwent laparoscopic supracervical hysterectomy or laparoscopic myomectomy with power morcellation at the hospital between 2006 and 2013.

Pathology of the morcellated uteri identified endometrial carcinoma in two patients (one with prolapse and one with a presumed prolapsing fibroid), for an incidence of 0.25%, according to Dr. Charles J. Ascher-Walsh, associate professor of obstetrics, gynecology, and reproductive science at Mount Sinai, and lead author of the study.

None of the patients were found to have a uterine sarcoma or any other cancer.

“There’s obviously very little data sort of looking forward on the risk of morcellating endometrial cancers. It doesn’t seem so far to significantly worsen the prognosis in these patients. There have been a few reviews looking at a cost-effectiveness analysis in biopsying postmenopausal asymptomatic patients who are having prolapse surgery, and so far the conclusions in both of those studies have shown that it’s not cost-effective to biopsy these patients,” Dr. Ascher-Walsh said. “Now I know there are institutions that are biopsying them anyway, and certainly as part of the revamp of people’s protocols with the morcellation debate, I think more institutions are starting to automatically biopsy every patient before morcellation.”

Total laparoscopic hysterectomies were not included in the study, because Dr. Ascher-Walsh usually performs that operation by vaginal approach, he said. “I wanted to focus just on the intra-abdominal morcellation technique. But obviously, in the debate, whether you cut into it vaginally or cut into it with an open myomectomy, you can potentially have the same concerns and risks.”

Mount Sinai has modified its policy on performing morcellation, somewhat, as a result of the ongoing debate, Dr. Ascher-Walsh said.

“We continue to do morcellation, but before doing morcellation, if we don’t have documentation of a typically growing fibroid, or if somebody presents with a large fibroid without any evidence of slow growth over time, we will get an MRI, although the evidence isn’t supportive of MRIs being diagnostic, other than the one study that combined it with [lactate dehydrogenase],” he said.

In the second study, a team led by Dr. Nichole Mahnert, a fellow in obstetrics and gynecology at the University of Michigan, Ann Arbor, used the Michigan Surgical Quality Collaborative database to prospectively study 6,360 women who underwent hysterectomy for a benign indication during 2013.

Pathology identified unexpected uterine sarcoma in 0.22% of patients (1 in 454) overall, and in 0.27% of patients (1 in 370) whose indication for surgery was specifically fibroids. These values are generally on par with the 0.28% of women operated on for fibroids (1 in 352) seen in the Food and Drug Administration assessment, she said.

In the cohort overall, prior venous thromboembolism and preoperative blood transfusion tended to be more common among patients later found to have uterine sarcoma.

Other cancers identified in the entire cohort included endometrial cancer (1.02%), ovarian cancer (1.06%), cervical cancer (0.17%), and metastatic cancer (0.20%).

“Comprehensive preoperative surgical counseling is paramount, and it should include not only the usual risks of surgery, but also the risk of unexpected malignancy and the risk of inadvertent morcellation of an unexpected malignancy. One should also consider the risks and benefits of a laparoscopic versus and open procedure,” Dr. Mahnert recommended. “And until we can more reliably risk-stratify patients to identify those with unexpected uterine sarcomas, we need to support technologies to limit the dissemination of specimens during minimally invasive procedures.”

In the third study, Dr. Katherine A. Hartzell, an ob.gyn. at Kaiser Permanente in San Diego, and her colleagues retrospectively reviewed the charts of all 3,523 women undergoing laparoscopic hysterectomy at the institution between 2001 and 2012.

Of the 941 cases in which power morcellation was used, uterine sarcoma was found in 6 cases or 0.6%; half were endometrial stromal sarcoma and half were leiomyosarcoma. Five of these patients had no evidence of disease after at least 31 months of follow-up. The sixth patient, who had high-grade leiomyosarcoma, died from her disease 3 years after diagnosis.

The uterine sarcoma rate of 0.6% was roughly double the 0.28% estimated by the FDA, Dr. Hartzell noted.

“This higher incidence was probably due to the inclusion of three patients with a delayed presentation of uterine sarcoma when initial pathology was benign,” she said. “These patients were likely discovered because of the captive nature of the Kaiser health care system.”

None of a wide variety of factors evaluated predicted the risk of uterine sarcoma in these patients undergoing morcellation, Dr. Hartzell said.

Among the 2,582 women who did not undergo power morcellation, uterine sarcoma was identified in 5 patients, or 0.2%. Four were alive without evidence of disease after at least 37 months of follow-up. The fifth patient, who had high-grade leiomyosarcoma, died from her disease 2 years after diagnosis.

“The patient about to undergo a minimally invasive procedure with possible power morcellation should be counseled about the possible consequences of morcellation of an undiagnosed malignancy. Alternatives such as mini-laparotomy or an open procedure should be offered. At our institution, we are also now performing morcellation within a tissue containment bag,” she said.

“Given the well-known advantages of laparoscopic surgery and the rarity of uterine sarcomas, it is our opinion that the risk of morcellation of occult malignancy is insufficient to abandon power morcellation,” Dr. Hartzell added.

The researchers reported that they had no relevant conflicts of interest.

SEATTLE– Two sets of simple clinical factors can help physicians identify which critically ill children with brain conditions are at highest risk for subclinical seizures and therefore most likely to benefit from continuous electroencephalographic (EEG) monitoring, according to a pair of studies reported at the annual meeting of the American Epilepsy Society.

Up to a third of patients with brain conditions in critical care units have seizures that are clinically silent, evident only on an EEG, Dr. Nicholas S. Abend, an assistant professor of neurology and pediatrics at the Children’s Hospital of Philadelphia, commented in a press briefing.

“There are more and more data that these seizures are associated with worse outcomes for patients – worse functional outcomes, lower quality of life later, and a higher risk for later epilepsy. And that’s led to a lot of interest in trying to monitor more and more patients in order to identify these seizures and treatment to manage them,” he said. But many hospitals have limited equipment and staff for continuous EEG monitoring and therefore face tough decisions in allocating these resources.

In the first study, Dr. Abend and his colleagues developed and validated a model to predict electrographic seizures in critically ill children with acute encephalopathic conditions.

They developed the model using retrospectively collected data from 336 consecutive children at multiple centers participating in the Critical Care EEG Monitoring Research Consortium. They then validated the model using prospectively collected data from 222 children at a single center, the Children’s Hospital of Philadelphia. Overall, about a third of the children had subclinical seizures.

“When we looked at predictors of seizures, we tried to keep it to things that a clinician would know pretty easily right on admission – not detailed data that might not be available until way later because they usually have to decide at the beginning, ‘Am I going to do EEG monitoring?’ ” Dr. Abend explained. The final model thus had five basic factors: age, etiology, clinically evident seizures before continuous EEG monitoring, initial EEG background pattern, and interictal epileptiform discharges.

Results presented in a poster session showed that the model had an area under the receiver operating characteristic curve of 0.845 in the development cohort and 0.799 in the validation cohort for identifying children who were experiencing subclinical seizures.

Intensive care units can select a model cutoff value based on the resources they have available for continuous EEG monitoring, noted Dr. Abend, who disclosed that he had no relevant conflicts of interest. “So, a center with very limited resources might decide, we only want to do this for really high-risk patients; a center with lots of resources could decide, we are going to apply things much more broadly, because we have EEG machines and we have EEG readers.”

With a broad model cutoff, for example, centers could go from monitoring all children to monitoring just half, with the trade-off of missing only about 10% of those who are having subclinical seizures. “This is not perfect, but few models of diagnostic tests are perfect,” Dr. Abend commented. “So I’ve taken this as pretty positive, that given the variability of going multicenter to single center with only five pretty basic data points, we can cut the monitoring in half and only miss about 10%.”

“In the next version of this study, with cleaner data and clearer criteria for who is getting included, and maybe including more data points, not just the five variables, we may be able to do a lot better. I think if we could cut the monitoring by half, and miss only 5% of patients, that’s not ideal, but maybe then it’s about developing other strategies to try to catch those 5% more efficiently, or at least giving centers with limited resources a logical approach” for deciding whom to monitor, he added.

In the second study, investigators led by Dr. Rajsekar R. Rajaraman, a pediatric neurology fellow at the University of California, Los Angeles, Medical Center, assessed predictors of early subclinical seizures among children with traumatic brain injury admitted to the pediatric intensive care unit. Early seizures were defined as those occurring within 7 days of the injury.

The investigators identified the predictors in a combined cohort of 135 consecutive children from the UCLA Medical Center and the Children’s Hospital of Colorado, and validated them in a cohort of 44 children from the Children’s Hospital of Philadelphia.

Overall, 12.6% of the development cohort and 31.8% of the validation cohort had subclinical seizures on EEG. “The really worrisome thing about subclinical seizures is that 87.1% of these patients who had subclinical seizures went on to have status epilepticus,” Dr. Rajaraman noted in the press briefing.

In a multivariate analysis, three factors predicted the risk of subclinical seizures: age younger than 2 years (odds ratio for older children, 0.84), abusive head trauma as the mechanism of injury (odds ratio, 7.29), and intradural hematoma on a computed tomography scan (odds ratio could not be calculated because this factor was present in all children with subclinical seizures). Findings were similar for the risk subclinical status epilepticus.

Notably, this set of factors worked similarly well in both the development cohort and the validation cohort, even though the latter had a greater severity of injury.

“All traumatic brain injury patients under the age of 2 [years] with intradural blood on CT should be placed on continuous video EEG,” recommended Dr. Rajaraman, who disclosed that he had no relevant conflicts of interest. “Additionally, if history suggests abusive head trauma, they are even more likely to have subclinical seizures.”

By using these factors to help identify these patients, “we can treat them sooner based on the video EEG monitoring. It’s also more cost-effective and more practical,” he added.

Dr. Jason T. Lerner a pediatric neurologist with UCLA Medical Center and a coinvestigator on the study, noted that the next step is to further test the factors’ validity in a broader population.

“Now we are working with the rest of the [Critical Care EEG Monitoring Research Consortium]. So we know the model works in two centers across the country on different coasts; now we are looking at another dozen different centers to see if this is something that does translate throughout the entire country, then hopefully even the world,” explained Dr. Lerner, who disclosed that he had no relevant conflicts of interest.

SEATTLE– Two sets of simple clinical factors can help physicians identify which critically ill children with brain conditions are at highest risk for subclinical seizures and therefore most likely to benefit from continuous electroencephalographic (EEG) monitoring, according to a pair of studies reported at the annual meeting of the American Epilepsy Society.

Up to a third of patients with brain conditions in critical care units have seizures that are clinically silent, evident only on an EEG, Dr. Nicholas S. Abend, an assistant professor of neurology and pediatrics at the Children’s Hospital of Philadelphia, commented in a press briefing.

“There are more and more data that these seizures are associated with worse outcomes for patients – worse functional outcomes, lower quality of life later, and a higher risk for later epilepsy. And that’s led to a lot of interest in trying to monitor more and more patients in order to identify these seizures and treatment to manage them,” he said. But many hospitals have limited equipment and staff for continuous EEG monitoring and therefore face tough decisions in allocating these resources.

In the first study, Dr. Abend and his colleagues developed and validated a model to predict electrographic seizures in critically ill children with acute encephalopathic conditions.

They developed the model using retrospectively collected data from 336 consecutive children at multiple centers participating in the Critical Care EEG Monitoring Research Consortium. They then validated the model using prospectively collected data from 222 children at a single center, the Children’s Hospital of Philadelphia. Overall, about a third of the children had subclinical seizures.

“When we looked at predictors of seizures, we tried to keep it to things that a clinician would know pretty easily right on admission – not detailed data that might not be available until way later because they usually have to decide at the beginning, ‘Am I going to do EEG monitoring?’ ” Dr. Abend explained. The final model thus had five basic factors: age, etiology, clinically evident seizures before continuous EEG monitoring, initial EEG background pattern, and interictal epileptiform discharges.

Results presented in a poster session showed that the model had an area under the receiver operating characteristic curve of 0.845 in the development cohort and 0.799 in the validation cohort for identifying children who were experiencing subclinical seizures.

Intensive care units can select a model cutoff value based on the resources they have available for continuous EEG monitoring, noted Dr. Abend, who disclosed that he had no relevant conflicts of interest. “So, a center with very limited resources might decide, we only want to do this for really high-risk patients; a center with lots of resources could decide, we are going to apply things much more broadly, because we have EEG machines and we have EEG readers.”

With a broad model cutoff, for example, centers could go from monitoring all children to monitoring just half, with the trade-off of missing only about 10% of those who are having subclinical seizures. “This is not perfect, but few models of diagnostic tests are perfect,” Dr. Abend commented. “So I’ve taken this as pretty positive, that given the variability of going multicenter to single center with only five pretty basic data points, we can cut the monitoring in half and only miss about 10%.”

“In the next version of this study, with cleaner data and clearer criteria for who is getting included, and maybe including more data points, not just the five variables, we may be able to do a lot better. I think if we could cut the monitoring by half, and miss only 5% of patients, that’s not ideal, but maybe then it’s about developing other strategies to try to catch those 5% more efficiently, or at least giving centers with limited resources a logical approach” for deciding whom to monitor, he added.

In the second study, investigators led by Dr. Rajsekar R. Rajaraman, a pediatric neurology fellow at the University of California, Los Angeles, Medical Center, assessed predictors of early subclinical seizures among children with traumatic brain injury admitted to the pediatric intensive care unit. Early seizures were defined as those occurring within 7 days of the injury.

The investigators identified the predictors in a combined cohort of 135 consecutive children from the UCLA Medical Center and the Children’s Hospital of Colorado, and validated them in a cohort of 44 children from the Children’s Hospital of Philadelphia.

Overall, 12.6% of the development cohort and 31.8% of the validation cohort had subclinical seizures on EEG. “The really worrisome thing about subclinical seizures is that 87.1% of these patients who had subclinical seizures went on to have status epilepticus,” Dr. Rajaraman noted in the press briefing.

In a multivariate analysis, three factors predicted the risk of subclinical seizures: age younger than 2 years (odds ratio for older children, 0.84), abusive head trauma as the mechanism of injury (odds ratio, 7.29), and intradural hematoma on a computed tomography scan (odds ratio could not be calculated because this factor was present in all children with subclinical seizures). Findings were similar for the risk subclinical status epilepticus.

Notably, this set of factors worked similarly well in both the development cohort and the validation cohort, even though the latter had a greater severity of injury.

“All traumatic brain injury patients under the age of 2 [years] with intradural blood on CT should be placed on continuous video EEG,” recommended Dr. Rajaraman, who disclosed that he had no relevant conflicts of interest. “Additionally, if history suggests abusive head trauma, they are even more likely to have subclinical seizures.”

By using these factors to help identify these patients, “we can treat them sooner based on the video EEG monitoring. It’s also more cost-effective and more practical,” he added.

Dr. Jason T. Lerner a pediatric neurologist with UCLA Medical Center and a coinvestigator on the study, noted that the next step is to further test the factors’ validity in a broader population.

“Now we are working with the rest of the [Critical Care EEG Monitoring Research Consortium]. So we know the model works in two centers across the country on different coasts; now we are looking at another dozen different centers to see if this is something that does translate throughout the entire country, then hopefully even the world,” explained Dr. Lerner, who disclosed that he had no relevant conflicts of interest.

SEATTLE– Two sets of simple clinical factors can help physicians identify which critically ill children with brain conditions are at highest risk for subclinical seizures and therefore most likely to benefit from continuous electroencephalographic (EEG) monitoring, according to a pair of studies reported at the annual meeting of the American Epilepsy Society.

Up to a third of patients with brain conditions in critical care units have seizures that are clinically silent, evident only on an EEG, Dr. Nicholas S. Abend, an assistant professor of neurology and pediatrics at the Children’s Hospital of Philadelphia, commented in a press briefing.

“There are more and more data that these seizures are associated with worse outcomes for patients – worse functional outcomes, lower quality of life later, and a higher risk for later epilepsy. And that’s led to a lot of interest in trying to monitor more and more patients in order to identify these seizures and treatment to manage them,” he said. But many hospitals have limited equipment and staff for continuous EEG monitoring and therefore face tough decisions in allocating these resources.

In the first study, Dr. Abend and his colleagues developed and validated a model to predict electrographic seizures in critically ill children with acute encephalopathic conditions.

They developed the model using retrospectively collected data from 336 consecutive children at multiple centers participating in the Critical Care EEG Monitoring Research Consortium. They then validated the model using prospectively collected data from 222 children at a single center, the Children’s Hospital of Philadelphia. Overall, about a third of the children had subclinical seizures.

“When we looked at predictors of seizures, we tried to keep it to things that a clinician would know pretty easily right on admission – not detailed data that might not be available until way later because they usually have to decide at the beginning, ‘Am I going to do EEG monitoring?’ ” Dr. Abend explained. The final model thus had five basic factors: age, etiology, clinically evident seizures before continuous EEG monitoring, initial EEG background pattern, and interictal epileptiform discharges.

Results presented in a poster session showed that the model had an area under the receiver operating characteristic curve of 0.845 in the development cohort and 0.799 in the validation cohort for identifying children who were experiencing subclinical seizures.

Intensive care units can select a model cutoff value based on the resources they have available for continuous EEG monitoring, noted Dr. Abend, who disclosed that he had no relevant conflicts of interest. “So, a center with very limited resources might decide, we only want to do this for really high-risk patients; a center with lots of resources could decide, we are going to apply things much more broadly, because we have EEG machines and we have EEG readers.”

With a broad model cutoff, for example, centers could go from monitoring all children to monitoring just half, with the trade-off of missing only about 10% of those who are having subclinical seizures. “This is not perfect, but few models of diagnostic tests are perfect,” Dr. Abend commented. “So I’ve taken this as pretty positive, that given the variability of going multicenter to single center with only five pretty basic data points, we can cut the monitoring in half and only miss about 10%.”

“In the next version of this study, with cleaner data and clearer criteria for who is getting included, and maybe including more data points, not just the five variables, we may be able to do a lot better. I think if we could cut the monitoring by half, and miss only 5% of patients, that’s not ideal, but maybe then it’s about developing other strategies to try to catch those 5% more efficiently, or at least giving centers with limited resources a logical approach” for deciding whom to monitor, he added.

In the second study, investigators led by Dr. Rajsekar R. Rajaraman, a pediatric neurology fellow at the University of California, Los Angeles, Medical Center, assessed predictors of early subclinical seizures among children with traumatic brain injury admitted to the pediatric intensive care unit. Early seizures were defined as those occurring within 7 days of the injury.

The investigators identified the predictors in a combined cohort of 135 consecutive children from the UCLA Medical Center and the Children’s Hospital of Colorado, and validated them in a cohort of 44 children from the Children’s Hospital of Philadelphia.

Overall, 12.6% of the development cohort and 31.8% of the validation cohort had subclinical seizures on EEG. “The really worrisome thing about subclinical seizures is that 87.1% of these patients who had subclinical seizures went on to have status epilepticus,” Dr. Rajaraman noted in the press briefing.

In a multivariate analysis, three factors predicted the risk of subclinical seizures: age younger than 2 years (odds ratio for older children, 0.84), abusive head trauma as the mechanism of injury (odds ratio, 7.29), and intradural hematoma on a computed tomography scan (odds ratio could not be calculated because this factor was present in all children with subclinical seizures). Findings were similar for the risk subclinical status epilepticus.

Notably, this set of factors worked similarly well in both the development cohort and the validation cohort, even though the latter had a greater severity of injury.

“All traumatic brain injury patients under the age of 2 [years] with intradural blood on CT should be placed on continuous video EEG,” recommended Dr. Rajaraman, who disclosed that he had no relevant conflicts of interest. “Additionally, if history suggests abusive head trauma, they are even more likely to have subclinical seizures.”

By using these factors to help identify these patients, “we can treat them sooner based on the video EEG monitoring. It’s also more cost-effective and more practical,” he added.

Dr. Jason T. Lerner a pediatric neurologist with UCLA Medical Center and a coinvestigator on the study, noted that the next step is to further test the factors’ validity in a broader population.

“Now we are working with the rest of the [Critical Care EEG Monitoring Research Consortium]. So we know the model works in two centers across the country on different coasts; now we are looking at another dozen different centers to see if this is something that does translate throughout the entire country, then hopefully even the world,” explained Dr. Lerner, who disclosed that he had no relevant conflicts of interest.

SEATTLE – An aggressive ketogenic diet is safe and usually successful in terminating status epilepticus in children that has not responded to optimal medical therapy, suggests a study presented at the annual meeting of the American Epilepsy Society.

The diet, in which the ratio of fat to protein and carbohydrate was pushed as high as 5:1 – more aggressive than in many protocols – broke the status epilepticus in 82% of cases, lead investigator Yeou-Mei Christiana Liu, a dietitian at the Hospital for Sick Children in Toronto, reported in a poster session.

And with monitoring of urine ketones and blood glucose levels four times daily and frequent adjustments of the ratio and caloric intake as needed, none of the children experienced adverse effects related to the diet.

“My recommendation would be not to worry. Try to be as aggressive as you can because they only need like a few days with the high diet ratio, and then they will be out of risk and can be extubated,” Ms. Liu advised in an interview. “And they should start the diet as soon as possible … we found that if we can start the ketogenic diet as early as possible, usually the chance for them to be out of the super-refractory status epilepticus condition is much better.”

“For safety, we had no trouble,” she further commented. “I know the number of patients is not high, but we used this approach for all these kids and we didn’t see any terrible side effects as long as we taught the ICU [intensive care unit] to follow our protocol and they made sure [the children did not experience excessive] ketoacidosis. We want [the urine ketone level] slightly above 16 mmol/L, but we don’t want to go too high.”

In the study, the investigators retrospectively reviewed the records of 10 children with 11 episodes of super-refractory status epilepticus. Prior to treatment with the ketogenic diet, the episodes had continued or recurred despite 24 hours of high-dose suppressive therapy.

The children ranged in age from 6 months to 13 years and were receiving care in the ICU. Clinicians had already tried at least four or five anticonvulsants, including combination therapy, in most cases.

All children were started on the classic ketogenic diet by nasogastric tube. Diet ratios and calories were initially tailored to patient weight, age, bowel routine, and concomitant treatment (especially any steroid therapy and intubation).

“We tried to start for the infants with a lower ratio, but we did make some diet changes” subsequently, noted Ms. Liu, who disclosed that she had no relevant conflicts of interest. “Next time, if I have a little one, I will start more aggressive, at a higher diet ratio.”

Results showed that in 10 of 11 episodes, ketosis was achieved during the first day of ketogenic diet treatment, she reported.

The diet was successful in terminating status epilepticus in 9 of 11 episodes. “We had a pretty good success rate,” she commented. “When we looked into other facilities’ protocol, with our protocol, we are more aggressive. So maybe that’s one of the reasons contributing to the success.”

The successful cases had earlier initiation of the diet after ICU admission (mean, 12 days vs. 41 days) and had consistently more moderate to high ketosis as seen in the urine ketone range (4 to more than 16 mmol/L vs. 0.5-16 mmol/L).

In the two episodes in which the diet did not terminate the status epilepticus, the children were receiving extra carbohydrate from medications or intravenous fluids. One additionally had fat malabsorption.

After the status epilepticus was broken, the dietary ratio was reduced but the children were kept on and sent home on the diet. “We started with a high diet ratio, and as soon as they were stable as far as seizure control, we started dropping the ratio because this is too high in fat, we worry about side effects. So we start dropping it, but we dropped it really slowly, to prevent a seizure recurrence,” Ms. Liu explained. She said that she had no relevant conflicts of interest.

SEATTLE – An aggressive ketogenic diet is safe and usually successful in terminating status epilepticus in children that has not responded to optimal medical therapy, suggests a study presented at the annual meeting of the American Epilepsy Society.

The diet, in which the ratio of fat to protein and carbohydrate was pushed as high as 5:1 – more aggressive than in many protocols – broke the status epilepticus in 82% of cases, lead investigator Yeou-Mei Christiana Liu, a dietitian at the Hospital for Sick Children in Toronto, reported in a poster session.

And with monitoring of urine ketones and blood glucose levels four times daily and frequent adjustments of the ratio and caloric intake as needed, none of the children experienced adverse effects related to the diet.

“My recommendation would be not to worry. Try to be as aggressive as you can because they only need like a few days with the high diet ratio, and then they will be out of risk and can be extubated,” Ms. Liu advised in an interview. “And they should start the diet as soon as possible … we found that if we can start the ketogenic diet as early as possible, usually the chance for them to be out of the super-refractory status epilepticus condition is much better.”

“For safety, we had no trouble,” she further commented. “I know the number of patients is not high, but we used this approach for all these kids and we didn’t see any terrible side effects as long as we taught the ICU [intensive care unit] to follow our protocol and they made sure [the children did not experience excessive] ketoacidosis. We want [the urine ketone level] slightly above 16 mmol/L, but we don’t want to go too high.”

In the study, the investigators retrospectively reviewed the records of 10 children with 11 episodes of super-refractory status epilepticus. Prior to treatment with the ketogenic diet, the episodes had continued or recurred despite 24 hours of high-dose suppressive therapy.

The children ranged in age from 6 months to 13 years and were receiving care in the ICU. Clinicians had already tried at least four or five anticonvulsants, including combination therapy, in most cases.

All children were started on the classic ketogenic diet by nasogastric tube. Diet ratios and calories were initially tailored to patient weight, age, bowel routine, and concomitant treatment (especially any steroid therapy and intubation).

“We tried to start for the infants with a lower ratio, but we did make some diet changes” subsequently, noted Ms. Liu, who disclosed that she had no relevant conflicts of interest. “Next time, if I have a little one, I will start more aggressive, at a higher diet ratio.”

Results showed that in 10 of 11 episodes, ketosis was achieved during the first day of ketogenic diet treatment, she reported.

The diet was successful in terminating status epilepticus in 9 of 11 episodes. “We had a pretty good success rate,” she commented. “When we looked into other facilities’ protocol, with our protocol, we are more aggressive. So maybe that’s one of the reasons contributing to the success.”

The successful cases had earlier initiation of the diet after ICU admission (mean, 12 days vs. 41 days) and had consistently more moderate to high ketosis as seen in the urine ketone range (4 to more than 16 mmol/L vs. 0.5-16 mmol/L).

In the two episodes in which the diet did not terminate the status epilepticus, the children were receiving extra carbohydrate from medications or intravenous fluids. One additionally had fat malabsorption.

After the status epilepticus was broken, the dietary ratio was reduced but the children were kept on and sent home on the diet. “We started with a high diet ratio, and as soon as they were stable as far as seizure control, we started dropping the ratio because this is too high in fat, we worry about side effects. So we start dropping it, but we dropped it really slowly, to prevent a seizure recurrence,” Ms. Liu explained. She said that she had no relevant conflicts of interest.

SEATTLE – An aggressive ketogenic diet is safe and usually successful in terminating status epilepticus in children that has not responded to optimal medical therapy, suggests a study presented at the annual meeting of the American Epilepsy Society.

The diet, in which the ratio of fat to protein and carbohydrate was pushed as high as 5:1 – more aggressive than in many protocols – broke the status epilepticus in 82% of cases, lead investigator Yeou-Mei Christiana Liu, a dietitian at the Hospital for Sick Children in Toronto, reported in a poster session.

And with monitoring of urine ketones and blood glucose levels four times daily and frequent adjustments of the ratio and caloric intake as needed, none of the children experienced adverse effects related to the diet.

“My recommendation would be not to worry. Try to be as aggressive as you can because they only need like a few days with the high diet ratio, and then they will be out of risk and can be extubated,” Ms. Liu advised in an interview. “And they should start the diet as soon as possible … we found that if we can start the ketogenic diet as early as possible, usually the chance for them to be out of the super-refractory status epilepticus condition is much better.”

“For safety, we had no trouble,” she further commented. “I know the number of patients is not high, but we used this approach for all these kids and we didn’t see any terrible side effects as long as we taught the ICU [intensive care unit] to follow our protocol and they made sure [the children did not experience excessive] ketoacidosis. We want [the urine ketone level] slightly above 16 mmol/L, but we don’t want to go too high.”

In the study, the investigators retrospectively reviewed the records of 10 children with 11 episodes of super-refractory status epilepticus. Prior to treatment with the ketogenic diet, the episodes had continued or recurred despite 24 hours of high-dose suppressive therapy.

The children ranged in age from 6 months to 13 years and were receiving care in the ICU. Clinicians had already tried at least four or five anticonvulsants, including combination therapy, in most cases.

All children were started on the classic ketogenic diet by nasogastric tube. Diet ratios and calories were initially tailored to patient weight, age, bowel routine, and concomitant treatment (especially any steroid therapy and intubation).

“We tried to start for the infants with a lower ratio, but we did make some diet changes” subsequently, noted Ms. Liu, who disclosed that she had no relevant conflicts of interest. “Next time, if I have a little one, I will start more aggressive, at a higher diet ratio.”

Results showed that in 10 of 11 episodes, ketosis was achieved during the first day of ketogenic diet treatment, she reported.

The diet was successful in terminating status epilepticus in 9 of 11 episodes. “We had a pretty good success rate,” she commented. “When we looked into other facilities’ protocol, with our protocol, we are more aggressive. So maybe that’s one of the reasons contributing to the success.”

The successful cases had earlier initiation of the diet after ICU admission (mean, 12 days vs. 41 days) and had consistently more moderate to high ketosis as seen in the urine ketone range (4 to more than 16 mmol/L vs. 0.5-16 mmol/L).

In the two episodes in which the diet did not terminate the status epilepticus, the children were receiving extra carbohydrate from medications or intravenous fluids. One additionally had fat malabsorption.

After the status epilepticus was broken, the dietary ratio was reduced but the children were kept on and sent home on the diet. “We started with a high diet ratio, and as soon as they were stable as far as seizure control, we started dropping the ratio because this is too high in fat, we worry about side effects. So we start dropping it, but we dropped it really slowly, to prevent a seizure recurrence,” Ms. Liu explained. She said that she had no relevant conflicts of interest.

SAN FRANCISCO – Obtaining palliative medicine consultations for geriatric trauma patients may help avoid futile interventions, suggests a retrospective cohort study reported at the annual clinical congress of the American College of Surgeons.

“The bulk of trauma in the United States has become geriatrics, and it’s falls from standing height,” noted lead investigator Dr. Christine C. Toevs, a trauma surgeon at Allegheny General Hospital in Pittsburgh; these older patients often have multiple comorbidities and are frail, and thus have a poor prognosis even with the best of care. “Clearly, this is a patient population that would benefit greatly from routine palliative medicine consultation,” she said.

Dr. Toevs and her colleagues performed a retrospective study of the charts of 5,261 trauma patients treated at their Level 1 trauma center during 2011-2013. One-third were geriatric, defined as aged 65 years or older.

Overall, 15% of geriatric patients and 2% of nongeriatric patients received a palliative medicine consult. The majority in both groups had a traumatic brain injury.

Within the geriatric age-group, about 90% of the patients who had a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 8% in this age-group overall, but 16% in the subset who received a consult.

“It seems that palliative medicine consult within the geriatric patient population does result in [fewer] procedures,” Dr. Toevs commented. “And studies have shown that when we talk to families and patients who participate in their care, they really do not want these procedures.”

Within the nongeriatric age–group, roughly 60% of patients with a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 3% in this age-group overall but 30% for those receiving the consult.

“Younger patients who receive palliative medicine consults seem to have the most severe injuries, not unexpectedly. These tend to be patients with the most severe traumatic brain injuries who still during their hospitalization are not demonstrating any signs of waking up. I think we all agree younger patients need a little more time than older patients, but some families don’t want to go down that route at all,” Dr. Toevs said. “So it’s reasonable before placing a trach in these patients with brain injuries, young or old, to have these discussions.”

Among all patients with a palliative medicine consult, geriatric patients were more likely to be discharged to a skilled nursing facility (32% vs. 15%), whereas nongeriatric patients were more likely to be discharged to a long-term acute care facility (13% vs. 5%) or rehabilitation facility (18% vs. 12%).

Whether avoiding long-term acute care facilities is a better outcome for geriatric patients “depends on how you look at it,” according to Dr. Toevs. “The bulk of the data suggest that 90% of all patients say that they really don’t want all that we do for them at the end of life, so most of us would consider this a better outcome.”

Three-fourths of all geriatric patients with a tracheostomy were discharged to a long-term acute care facility, although data suggest that few such patients survive to discharge. “So what we are doing is we are relocating the death rather than actually addressing the issues of what kind of life do they want,” she commented. “Do they really want the end of their lives to be in an ICU or a step-down ICU in a long-term acute care hospital? So if the patients ultimately get trached, the outcomes tend to be much worse as you can imagine and, in my mind, we have not done nearly as good a job as we should have initially; we should have in some way preempted this, and we didn’t explain to everyone well enough that this really was not considered a good outcome.”

The investigators plan further research in this area, according to Dr. Toevs, who disclosed that she had no relevant conflicts of interest. “We are looking at long-term survival data if we do send them to places after geriatric trauma – what really happens to them, what’s their survival at 6 months and a year – so that we can give [these] data to their families,” she elaborated. “We are also working with our rehab doctors to look at functional assessments and prognostication of these patients, and ultimately, really being able to quantify the benefits of palliative medicine and the goals of care discussions with these patients.”

Invited discussant Dr. Henri R. Ford, chief of surgery at the Children’s Hospital Los Angeles asked, “What were the specific criteria used, on average, to decide whether somebody should get a palliative medicine consultation? Have you tried to standardize that pretty much across the board for all of your trauma patients?”

Use of these consults at her hospital has increased since she began pushing for them, according to Dr. Toevs. “What I would like to do is to make it as routine as possible – every person on the trauma service gets a rehab consult; to some degree, every person on the trauma service should get a palliative medicine consult. It ought to be a checkbox. We are not quite there yet. But right now, I’m pushing for 80% and above, just to make it routine to begin the discussion: Do they have an advance directive? Do they have a power of attorney? Have they thought about these things long term?”

“Did you also compare the injury severity scores for the various patients, not only for the geriatric but also for those who received palliative medicine consultations versus those who did not?” Dr. Ford further asked. “That would be very, very interesting for us in terms of understanding selection bias.”

The investigators looked at these scores in another study, finding that they were lower for geriatric patients than for nongeriatric patients, as expected. “But because of their frailty, they do much poorer. And we are trying to correlate that long term when we are working with our rehab doctors and trying to look at the ability to prognosticate basically upon functional status prior to injury.”

Dr. Toevs disclosed that she had no relevant conflicts of interest.

SAN FRANCISCO – Obtaining palliative medicine consultations for geriatric trauma patients may help avoid futile interventions, suggests a retrospective cohort study reported at the annual clinical congress of the American College of Surgeons.

“The bulk of trauma in the United States has become geriatrics, and it’s falls from standing height,” noted lead investigator Dr. Christine C. Toevs, a trauma surgeon at Allegheny General Hospital in Pittsburgh; these older patients often have multiple comorbidities and are frail, and thus have a poor prognosis even with the best of care. “Clearly, this is a patient population that would benefit greatly from routine palliative medicine consultation,” she said.

Dr. Toevs and her colleagues performed a retrospective study of the charts of 5,261 trauma patients treated at their Level 1 trauma center during 2011-2013. One-third were geriatric, defined as aged 65 years or older.

Overall, 15% of geriatric patients and 2% of nongeriatric patients received a palliative medicine consult. The majority in both groups had a traumatic brain injury.

Within the geriatric age-group, about 90% of the patients who had a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 8% in this age-group overall, but 16% in the subset who received a consult.

“It seems that palliative medicine consult within the geriatric patient population does result in [fewer] procedures,” Dr. Toevs commented. “And studies have shown that when we talk to families and patients who participate in their care, they really do not want these procedures.”

Within the nongeriatric age–group, roughly 60% of patients with a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 3% in this age-group overall but 30% for those receiving the consult.

“Younger patients who receive palliative medicine consults seem to have the most severe injuries, not unexpectedly. These tend to be patients with the most severe traumatic brain injuries who still during their hospitalization are not demonstrating any signs of waking up. I think we all agree younger patients need a little more time than older patients, but some families don’t want to go down that route at all,” Dr. Toevs said. “So it’s reasonable before placing a trach in these patients with brain injuries, young or old, to have these discussions.”

Among all patients with a palliative medicine consult, geriatric patients were more likely to be discharged to a skilled nursing facility (32% vs. 15%), whereas nongeriatric patients were more likely to be discharged to a long-term acute care facility (13% vs. 5%) or rehabilitation facility (18% vs. 12%).

Whether avoiding long-term acute care facilities is a better outcome for geriatric patients “depends on how you look at it,” according to Dr. Toevs. “The bulk of the data suggest that 90% of all patients say that they really don’t want all that we do for them at the end of life, so most of us would consider this a better outcome.”

Three-fourths of all geriatric patients with a tracheostomy were discharged to a long-term acute care facility, although data suggest that few such patients survive to discharge. “So what we are doing is we are relocating the death rather than actually addressing the issues of what kind of life do they want,” she commented. “Do they really want the end of their lives to be in an ICU or a step-down ICU in a long-term acute care hospital? So if the patients ultimately get trached, the outcomes tend to be much worse as you can imagine and, in my mind, we have not done nearly as good a job as we should have initially; we should have in some way preempted this, and we didn’t explain to everyone well enough that this really was not considered a good outcome.”

The investigators plan further research in this area, according to Dr. Toevs, who disclosed that she had no relevant conflicts of interest. “We are looking at long-term survival data if we do send them to places after geriatric trauma – what really happens to them, what’s their survival at 6 months and a year – so that we can give [these] data to their families,” she elaborated. “We are also working with our rehab doctors to look at functional assessments and prognostication of these patients, and ultimately, really being able to quantify the benefits of palliative medicine and the goals of care discussions with these patients.”

Invited discussant Dr. Henri R. Ford, chief of surgery at the Children’s Hospital Los Angeles asked, “What were the specific criteria used, on average, to decide whether somebody should get a palliative medicine consultation? Have you tried to standardize that pretty much across the board for all of your trauma patients?”

Use of these consults at her hospital has increased since she began pushing for them, according to Dr. Toevs. “What I would like to do is to make it as routine as possible – every person on the trauma service gets a rehab consult; to some degree, every person on the trauma service should get a palliative medicine consult. It ought to be a checkbox. We are not quite there yet. But right now, I’m pushing for 80% and above, just to make it routine to begin the discussion: Do they have an advance directive? Do they have a power of attorney? Have they thought about these things long term?”

“Did you also compare the injury severity scores for the various patients, not only for the geriatric but also for those who received palliative medicine consultations versus those who did not?” Dr. Ford further asked. “That would be very, very interesting for us in terms of understanding selection bias.”

The investigators looked at these scores in another study, finding that they were lower for geriatric patients than for nongeriatric patients, as expected. “But because of their frailty, they do much poorer. And we are trying to correlate that long term when we are working with our rehab doctors and trying to look at the ability to prognosticate basically upon functional status prior to injury.”

Dr. Toevs disclosed that she had no relevant conflicts of interest.

SAN FRANCISCO – Obtaining palliative medicine consultations for geriatric trauma patients may help avoid futile interventions, suggests a retrospective cohort study reported at the annual clinical congress of the American College of Surgeons.

“The bulk of trauma in the United States has become geriatrics, and it’s falls from standing height,” noted lead investigator Dr. Christine C. Toevs, a trauma surgeon at Allegheny General Hospital in Pittsburgh; these older patients often have multiple comorbidities and are frail, and thus have a poor prognosis even with the best of care. “Clearly, this is a patient population that would benefit greatly from routine palliative medicine consultation,” she said.

Dr. Toevs and her colleagues performed a retrospective study of the charts of 5,261 trauma patients treated at their Level 1 trauma center during 2011-2013. One-third were geriatric, defined as aged 65 years or older.

Overall, 15% of geriatric patients and 2% of nongeriatric patients received a palliative medicine consult. The majority in both groups had a traumatic brain injury.

Within the geriatric age-group, about 90% of the patients who had a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 8% in this age-group overall, but 16% in the subset who received a consult.

“It seems that palliative medicine consult within the geriatric patient population does result in [fewer] procedures,” Dr. Toevs commented. “And studies have shown that when we talk to families and patients who participate in their care, they really do not want these procedures.”

Within the nongeriatric age–group, roughly 60% of patients with a consult did not undergo tracheostomy and percutaneous endoscopic gastrostomy (PEG) tube placement. Mortality was about 3% in this age-group overall but 30% for those receiving the consult.

“Younger patients who receive palliative medicine consults seem to have the most severe injuries, not unexpectedly. These tend to be patients with the most severe traumatic brain injuries who still during their hospitalization are not demonstrating any signs of waking up. I think we all agree younger patients need a little more time than older patients, but some families don’t want to go down that route at all,” Dr. Toevs said. “So it’s reasonable before placing a trach in these patients with brain injuries, young or old, to have these discussions.”

Among all patients with a palliative medicine consult, geriatric patients were more likely to be discharged to a skilled nursing facility (32% vs. 15%), whereas nongeriatric patients were more likely to be discharged to a long-term acute care facility (13% vs. 5%) or rehabilitation facility (18% vs. 12%).

Whether avoiding long-term acute care facilities is a better outcome for geriatric patients “depends on how you look at it,” according to Dr. Toevs. “The bulk of the data suggest that 90% of all patients say that they really don’t want all that we do for them at the end of life, so most of us would consider this a better outcome.”

Three-fourths of all geriatric patients with a tracheostomy were discharged to a long-term acute care facility, although data suggest that few such patients survive to discharge. “So what we are doing is we are relocating the death rather than actually addressing the issues of what kind of life do they want,” she commented. “Do they really want the end of their lives to be in an ICU or a step-down ICU in a long-term acute care hospital? So if the patients ultimately get trached, the outcomes tend to be much worse as you can imagine and, in my mind, we have not done nearly as good a job as we should have initially; we should have in some way preempted this, and we didn’t explain to everyone well enough that this really was not considered a good outcome.”

The investigators plan further research in this area, according to Dr. Toevs, who disclosed that she had no relevant conflicts of interest. “We are looking at long-term survival data if we do send them to places after geriatric trauma – what really happens to them, what’s their survival at 6 months and a year – so that we can give [these] data to their families,” she elaborated. “We are also working with our rehab doctors to look at functional assessments and prognostication of these patients, and ultimately, really being able to quantify the benefits of palliative medicine and the goals of care discussions with these patients.”

Invited discussant Dr. Henri R. Ford, chief of surgery at the Children’s Hospital Los Angeles asked, “What were the specific criteria used, on average, to decide whether somebody should get a palliative medicine consultation? Have you tried to standardize that pretty much across the board for all of your trauma patients?”

Use of these consults at her hospital has increased since she began pushing for them, according to Dr. Toevs. “What I would like to do is to make it as routine as possible – every person on the trauma service gets a rehab consult; to some degree, every person on the trauma service should get a palliative medicine consult. It ought to be a checkbox. We are not quite there yet. But right now, I’m pushing for 80% and above, just to make it routine to begin the discussion: Do they have an advance directive? Do they have a power of attorney? Have they thought about these things long term?”

“Did you also compare the injury severity scores for the various patients, not only for the geriatric but also for those who received palliative medicine consultations versus those who did not?” Dr. Ford further asked. “That would be very, very interesting for us in terms of understanding selection bias.”

The investigators looked at these scores in another study, finding that they were lower for geriatric patients than for nongeriatric patients, as expected. “But because of their frailty, they do much poorer. And we are trying to correlate that long term when we are working with our rehab doctors and trying to look at the ability to prognosticate basically upon functional status prior to injury.”

Dr. Toevs disclosed that she had no relevant conflicts of interest.

SAN FRANCISCO– Positive regional lymph nodes are not an independent risk factor for death from adrenocortical carcinoma, finds a cohort study presented at the annual clinical congress of the American College of Surgeons.

“High tumor grade and distant metastasis were the only independent prognostic factors,” reported lead researcher Dr. Kun-Tai Hsu, a surgical resident formerly with the University of Wisconsin–Madison and currently at Michigan State University in East Lansing.

“While regional lymph node metastasis was not associated with worse outcome, it was associated with local tumor invasion. More importantly, regional lymph node status and local tumor invasion had equivalent impact on disease-specific mortality, but lymph node status was not a marker for local tumor invasion,” he added.

Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers analyzed data for 1,202 adults who underwent surgery for unilateral adrenocortical carcinoma between 1973 and 2010. A total of 10% had regional lymph node metastases, as ascertained by sampling, imaging, or both.

Median survival was 46 months for the cohort overall, and the 5-year rate of disease-specific mortality was 55%, Dr. Hsu reported. Patients with regional lymph node metastases had higher significantly disease-specific mortality in unadjusted analyses but not in adjusted analysis. However, high tumor grade and distant metastases were both strong independent risk factors (hazard ratios, 2.37 and 2.87).

Patients were more likely to have regional lymph node metastases if they had local invasion. When peers having neither of these factors were the comparator, risk was elevated for patients with only positive lymph nodes (HR, 9.9) and for patients with only local invasion (HR, 6.7), and most for patients having both factors (HR, 18.0).

“The effect appears to be additive rather than a true interaction,” commented Dr. Hsu, who disclosed that he had no conflicts of interest relevant to the research. “Therefore, there was no synergistic interaction between local tumor invasion and regional lymph node metastases: these two disease factors equally predict disease-specific mortality and are not simply a marker of one another.”

“We are aware that there are several limitations of the SEER database,” he acknowledged. “Nevertheless, given the rare nature of adrenocortical carcinoma, SEER provided enough data to have the statistical power and objectivity not available from single-institution studies.”

In an interview, session comoderator Dr. Amelia C. Grover of the Department of Surgery’s division of surgical oncology, Virginia Commonwealth University in Richmond, said that the findings reinforce earlier research on this cancer. “The problem is, adrenocortical carcinoma is such a uncommon disease, it makes drawing a large enough group difficult. So the SEER database was a great resource,” she agreed. “However, because of its limitations, it makes it hard to draw any significant conclusions, again stressing that for these unusual endocrine neoplasms, it’s really great to have collaborative efforts from multiple institutions in driving that research forward and collecting that data so that we can better care for those patients.”

SAN FRANCISCO– Positive regional lymph nodes are not an independent risk factor for death from adrenocortical carcinoma, finds a cohort study presented at the annual clinical congress of the American College of Surgeons.

“High tumor grade and distant metastasis were the only independent prognostic factors,” reported lead researcher Dr. Kun-Tai Hsu, a surgical resident formerly with the University of Wisconsin–Madison and currently at Michigan State University in East Lansing.

“While regional lymph node metastasis was not associated with worse outcome, it was associated with local tumor invasion. More importantly, regional lymph node status and local tumor invasion had equivalent impact on disease-specific mortality, but lymph node status was not a marker for local tumor invasion,” he added.

Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers analyzed data for 1,202 adults who underwent surgery for unilateral adrenocortical carcinoma between 1973 and 2010. A total of 10% had regional lymph node metastases, as ascertained by sampling, imaging, or both.

Median survival was 46 months for the cohort overall, and the 5-year rate of disease-specific mortality was 55%, Dr. Hsu reported. Patients with regional lymph node metastases had higher significantly disease-specific mortality in unadjusted analyses but not in adjusted analysis. However, high tumor grade and distant metastases were both strong independent risk factors (hazard ratios, 2.37 and 2.87).

Patients were more likely to have regional lymph node metastases if they had local invasion. When peers having neither of these factors were the comparator, risk was elevated for patients with only positive lymph nodes (HR, 9.9) and for patients with only local invasion (HR, 6.7), and most for patients having both factors (HR, 18.0).

“The effect appears to be additive rather than a true interaction,” commented Dr. Hsu, who disclosed that he had no conflicts of interest relevant to the research. “Therefore, there was no synergistic interaction between local tumor invasion and regional lymph node metastases: these two disease factors equally predict disease-specific mortality and are not simply a marker of one another.”

“We are aware that there are several limitations of the SEER database,” he acknowledged. “Nevertheless, given the rare nature of adrenocortical carcinoma, SEER provided enough data to have the statistical power and objectivity not available from single-institution studies.”

In an interview, session comoderator Dr. Amelia C. Grover of the Department of Surgery’s division of surgical oncology, Virginia Commonwealth University in Richmond, said that the findings reinforce earlier research on this cancer. “The problem is, adrenocortical carcinoma is such a uncommon disease, it makes drawing a large enough group difficult. So the SEER database was a great resource,” she agreed. “However, because of its limitations, it makes it hard to draw any significant conclusions, again stressing that for these unusual endocrine neoplasms, it’s really great to have collaborative efforts from multiple institutions in driving that research forward and collecting that data so that we can better care for those patients.”

SAN FRANCISCO– Positive regional lymph nodes are not an independent risk factor for death from adrenocortical carcinoma, finds a cohort study presented at the annual clinical congress of the American College of Surgeons.

“High tumor grade and distant metastasis were the only independent prognostic factors,” reported lead researcher Dr. Kun-Tai Hsu, a surgical resident formerly with the University of Wisconsin–Madison and currently at Michigan State University in East Lansing.

“While regional lymph node metastasis was not associated with worse outcome, it was associated with local tumor invasion. More importantly, regional lymph node status and local tumor invasion had equivalent impact on disease-specific mortality, but lymph node status was not a marker for local tumor invasion,” he added.

Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers analyzed data for 1,202 adults who underwent surgery for unilateral adrenocortical carcinoma between 1973 and 2010. A total of 10% had regional lymph node metastases, as ascertained by sampling, imaging, or both.

Median survival was 46 months for the cohort overall, and the 5-year rate of disease-specific mortality was 55%, Dr. Hsu reported. Patients with regional lymph node metastases had higher significantly disease-specific mortality in unadjusted analyses but not in adjusted analysis. However, high tumor grade and distant metastases were both strong independent risk factors (hazard ratios, 2.37 and 2.87).

Patients were more likely to have regional lymph node metastases if they had local invasion. When peers having neither of these factors were the comparator, risk was elevated for patients with only positive lymph nodes (HR, 9.9) and for patients with only local invasion (HR, 6.7), and most for patients having both factors (HR, 18.0).

“The effect appears to be additive rather than a true interaction,” commented Dr. Hsu, who disclosed that he had no conflicts of interest relevant to the research. “Therefore, there was no synergistic interaction between local tumor invasion and regional lymph node metastases: these two disease factors equally predict disease-specific mortality and are not simply a marker of one another.”

“We are aware that there are several limitations of the SEER database,” he acknowledged. “Nevertheless, given the rare nature of adrenocortical carcinoma, SEER provided enough data to have the statistical power and objectivity not available from single-institution studies.”

In an interview, session comoderator Dr. Amelia C. Grover of the Department of Surgery’s division of surgical oncology, Virginia Commonwealth University in Richmond, said that the findings reinforce earlier research on this cancer. “The problem is, adrenocortical carcinoma is such a uncommon disease, it makes drawing a large enough group difficult. So the SEER database was a great resource,” she agreed. “However, because of its limitations, it makes it hard to draw any significant conclusions, again stressing that for these unusual endocrine neoplasms, it’s really great to have collaborative efforts from multiple institutions in driving that research forward and collecting that data so that we can better care for those patients.”