Literature Review

Levetiracetam monotherapy, controlled-release carbamazepine monotherapy, and lamotrigine monotherapy have similar efficacy among elderly adults with new-onset focal epilepsy, according to research published in the March issue of Epilepsia. Levetiracetam has superior tolerability in this population, however, compared with controlled-release carbamazepine. Lamotrigine’s tolerability may be between those of levetiracetam and carbamazepine.

“This randomized-controlled trial provides evidence supporting the use of levetiracetam as first-line treatment for elderly patients with new-onset focal epilepsy and points to the value of lamotrigine as an alternative [to levetiracetam],” said Konrad J. Werhahn, MD, Professor of Neurology at the University Medical Center of the Johannes Gutenberg University in Mainz, Germany.

Half of all newly occurring epileptic seizures are expected to occur in patients age 60 and older in 2020. Few trials have evaluated treatment options for these patients, however. Observational data suggesting that levetiracetam may be effective in this population prompted Dr. Werhahn and colleagues to conduct a comparative trial.

A Yearlong Maintenance Period
Between March 2007 and August 2011, the investigators randomized 361 patients to controlled-release carbamazepine, lamotrigine, or levetiracetam. Eligible participants were age 60 or older and had new-onset focal epilepsy. The researchers excluded patients with symptomatic seizures occurring less than two weeks after the onset of acute cerebral insults and patients previously treated with valproate within four weeks of screening.

During a six-week period, doses were titrated to initial target amounts of 400 mg/day of carbamazepine, 100 mg/day of lamotrigine, or 1,000 mg/day of levetiracetam. The investigators selected these doses based on previous studies in the elderly. A 52-week maintenance period followed the titration period. Dose adjustments were allowed during the maintenance period to address concerns about tolerability and seizure control. Patients were withdrawn if they did not tolerate doses within this range or if they had recurrent seizures despite receiving the maximum dose.

The trial’s primary outcome measure was the retention rate at week 58, as measured from day 1 of treatment. Secondary outcome measures included seizure-freedom rates at weeks 30 and 58, time to first seizure, and time to first drug-related adverse event.

Adverse Events Occurred Earlier With Carbamazepine
The retention rate at week 58 was 45.8% for carbamazepine, 55.6% for lamotrigine, and 61.5% for levetiracetam. Retention rates were significantly different for all groups. Logistic regression analysis suggested that the number of concomitant diseases influenced retention at week 58.

The researchers found no significant differences in rates of seizure freedom at week 30 or at week 58. The rate of seizure freedom at week 58 was 33.3% for carbamazepine, 38.5% for lamotrigine, and 42.6% for levetiracetam. The time to first seizure after randomization or after titration was similar between treatment arms.

The incidence of reported adverse events was similar between treatment groups. Most adverse events were of mild to moderate severity. The most common adverse events were dizziness, fatigue, and headache. Adverse events occurred earlier with carbamazepine than with the other drugs. Also, more discontinuations due to adverse events occurred in the carbamazepine group than in the other groups.

“To our knowledge, the present trial is the first prospective comparison of levetiracetam with the optimal and most widely used formulation (controlled-release) of carbamazepine in this population,” said Dr. Werhahn, who receives compensation for activities with UCB Pharma. “Average doses of the drugs during the trial were all lower than the predefined target doses (most notably for carbamazepine), and also lower than those recommended in the individual product labels. This [datum] supports the recommendation that initial dosing of epilepsy medication for elderly patients should be lower, with a slower titration schedule than that used in younger adults, to reduce the risk of tolerability issues.

Although the study was not powered for the inclusion of the lamotrigine arm, “clear differences were evident in the tolerability profiles of these drugs during the trial, suggesting that the differences in retention rates at week 58 were driven primarily by the drugs’ tolerability profiles, rather than their efficacy,” Dr. Werhahn concluded.

—Erik Greb

Levetiracetam monotherapy, controlled-release carbamazepine monotherapy, and lamotrigine monotherapy have similar efficacy among elderly adults with new-onset focal epilepsy, according to research published in the March issue of Epilepsia. Levetiracetam has superior tolerability in this population, however, compared with controlled-release carbamazepine. Lamotrigine’s tolerability may be between those of levetiracetam and carbamazepine.

“This randomized-controlled trial provides evidence supporting the use of levetiracetam as first-line treatment for elderly patients with new-onset focal epilepsy and points to the value of lamotrigine as an alternative [to levetiracetam],” said Konrad J. Werhahn, MD, Professor of Neurology at the University Medical Center of the Johannes Gutenberg University in Mainz, Germany.

Half of all newly occurring epileptic seizures are expected to occur in patients age 60 and older in 2020. Few trials have evaluated treatment options for these patients, however. Observational data suggesting that levetiracetam may be effective in this population prompted Dr. Werhahn and colleagues to conduct a comparative trial.

A Yearlong Maintenance Period
Between March 2007 and August 2011, the investigators randomized 361 patients to controlled-release carbamazepine, lamotrigine, or levetiracetam. Eligible participants were age 60 or older and had new-onset focal epilepsy. The researchers excluded patients with symptomatic seizures occurring less than two weeks after the onset of acute cerebral insults and patients previously treated with valproate within four weeks of screening.

During a six-week period, doses were titrated to initial target amounts of 400 mg/day of carbamazepine, 100 mg/day of lamotrigine, or 1,000 mg/day of levetiracetam. The investigators selected these doses based on previous studies in the elderly. A 52-week maintenance period followed the titration period. Dose adjustments were allowed during the maintenance period to address concerns about tolerability and seizure control. Patients were withdrawn if they did not tolerate doses within this range or if they had recurrent seizures despite receiving the maximum dose.

The trial’s primary outcome measure was the retention rate at week 58, as measured from day 1 of treatment. Secondary outcome measures included seizure-freedom rates at weeks 30 and 58, time to first seizure, and time to first drug-related adverse event.

Adverse Events Occurred Earlier With Carbamazepine
The retention rate at week 58 was 45.8% for carbamazepine, 55.6% for lamotrigine, and 61.5% for levetiracetam. Retention rates were significantly different for all groups. Logistic regression analysis suggested that the number of concomitant diseases influenced retention at week 58.

The researchers found no significant differences in rates of seizure freedom at week 30 or at week 58. The rate of seizure freedom at week 58 was 33.3% for carbamazepine, 38.5% for lamotrigine, and 42.6% for levetiracetam. The time to first seizure after randomization or after titration was similar between treatment arms.

The incidence of reported adverse events was similar between treatment groups. Most adverse events were of mild to moderate severity. The most common adverse events were dizziness, fatigue, and headache. Adverse events occurred earlier with carbamazepine than with the other drugs. Also, more discontinuations due to adverse events occurred in the carbamazepine group than in the other groups.

“To our knowledge, the present trial is the first prospective comparison of levetiracetam with the optimal and most widely used formulation (controlled-release) of carbamazepine in this population,” said Dr. Werhahn, who receives compensation for activities with UCB Pharma. “Average doses of the drugs during the trial were all lower than the predefined target doses (most notably for carbamazepine), and also lower than those recommended in the individual product labels. This [datum] supports the recommendation that initial dosing of epilepsy medication for elderly patients should be lower, with a slower titration schedule than that used in younger adults, to reduce the risk of tolerability issues.

Although the study was not powered for the inclusion of the lamotrigine arm, “clear differences were evident in the tolerability profiles of these drugs during the trial, suggesting that the differences in retention rates at week 58 were driven primarily by the drugs’ tolerability profiles, rather than their efficacy,” Dr. Werhahn concluded.

—Erik Greb

Levetiracetam monotherapy, controlled-release carbamazepine monotherapy, and lamotrigine monotherapy have similar efficacy among elderly adults with new-onset focal epilepsy, according to research published in the March issue of Epilepsia. Levetiracetam has superior tolerability in this population, however, compared with controlled-release carbamazepine. Lamotrigine’s tolerability may be between those of levetiracetam and carbamazepine.

“This randomized-controlled trial provides evidence supporting the use of levetiracetam as first-line treatment for elderly patients with new-onset focal epilepsy and points to the value of lamotrigine as an alternative [to levetiracetam],” said Konrad J. Werhahn, MD, Professor of Neurology at the University Medical Center of the Johannes Gutenberg University in Mainz, Germany.

Half of all newly occurring epileptic seizures are expected to occur in patients age 60 and older in 2020. Few trials have evaluated treatment options for these patients, however. Observational data suggesting that levetiracetam may be effective in this population prompted Dr. Werhahn and colleagues to conduct a comparative trial.

A Yearlong Maintenance Period
Between March 2007 and August 2011, the investigators randomized 361 patients to controlled-release carbamazepine, lamotrigine, or levetiracetam. Eligible participants were age 60 or older and had new-onset focal epilepsy. The researchers excluded patients with symptomatic seizures occurring less than two weeks after the onset of acute cerebral insults and patients previously treated with valproate within four weeks of screening.

During a six-week period, doses were titrated to initial target amounts of 400 mg/day of carbamazepine, 100 mg/day of lamotrigine, or 1,000 mg/day of levetiracetam. The investigators selected these doses based on previous studies in the elderly. A 52-week maintenance period followed the titration period. Dose adjustments were allowed during the maintenance period to address concerns about tolerability and seizure control. Patients were withdrawn if they did not tolerate doses within this range or if they had recurrent seizures despite receiving the maximum dose.

The trial’s primary outcome measure was the retention rate at week 58, as measured from day 1 of treatment. Secondary outcome measures included seizure-freedom rates at weeks 30 and 58, time to first seizure, and time to first drug-related adverse event.

Adverse Events Occurred Earlier With Carbamazepine
The retention rate at week 58 was 45.8% for carbamazepine, 55.6% for lamotrigine, and 61.5% for levetiracetam. Retention rates were significantly different for all groups. Logistic regression analysis suggested that the number of concomitant diseases influenced retention at week 58.

The researchers found no significant differences in rates of seizure freedom at week 30 or at week 58. The rate of seizure freedom at week 58 was 33.3% for carbamazepine, 38.5% for lamotrigine, and 42.6% for levetiracetam. The time to first seizure after randomization or after titration was similar between treatment arms.

The incidence of reported adverse events was similar between treatment groups. Most adverse events were of mild to moderate severity. The most common adverse events were dizziness, fatigue, and headache. Adverse events occurred earlier with carbamazepine than with the other drugs. Also, more discontinuations due to adverse events occurred in the carbamazepine group than in the other groups.

“To our knowledge, the present trial is the first prospective comparison of levetiracetam with the optimal and most widely used formulation (controlled-release) of carbamazepine in this population,” said Dr. Werhahn, who receives compensation for activities with UCB Pharma. “Average doses of the drugs during the trial were all lower than the predefined target doses (most notably for carbamazepine), and also lower than those recommended in the individual product labels. This [datum] supports the recommendation that initial dosing of epilepsy medication for elderly patients should be lower, with a slower titration schedule than that used in younger adults, to reduce the risk of tolerability issues.

Although the study was not powered for the inclusion of the lamotrigine arm, “clear differences were evident in the tolerability profiles of these drugs during the trial, suggesting that the differences in retention rates at week 58 were driven primarily by the drugs’ tolerability profiles, rather than their efficacy,” Dr. Werhahn concluded.

—Erik Greb

For patients with multiple sclerosis (MS), having no evidence of disease activity (NEDA) at two years has a positive predictive value of 78.3% for absence of progression at seven years, according to research published in the February issue of JAMA Neurology.

Although 46% of patients in the study had achieved NEDA at one year, 7.9% of patients maintained NEDA after seven years. These findings result from a longitudinal study of 215 patients with clinically isolated syndrome or relapsing-remitting MS.

Dalia L. Rotstein, MD, Assistant Professor of Neurology at the University of Toronto, and her colleagues analyzed data for members of the Comprehensive Longitudinal Investigation of MS at Brigham and Women’s Hospital (CLIMB) cohort who had a minimum of seven years of prospective MRI and clinical follow-up data.

The concept of NEDA is common in the treatment of diseases such as cancer and rheumatoid arthritis, but is considered a secondary outcome measure in MS. NEDA is defined as the absence of new or enlarging T2 lesions or T1 gadolinium-enhancing lesions on MRI and the absence of sustained Expanded Disability Status Scale score progression or clinical relapse.

During the study period, clinical and MRI indicators of disease progress were dissociated, said the investigators. The percentage of patients who had no evidence of disease progression on one measure but not on another ranged from 42.9% at year 2 to 30.6% at year 7. No MRI disease activity occurred in 23.5% of patients at year 1 and in 14.8% of patients at year 7, but the percentage of participants who had NEDA was about 15% at both time points.

“Although NEDA has the potential to become not only a key outcome measure of disease-modifying therapy, but also a treat-to-target goal, it will require a comprehensive approach that integrates advances in MRI technology, linkage of blood and CSF biomarkers, and a high degree of cooperation among investigators,” said the authors.

The study did not explore the effects of different treatment approaches, but NEDA is a necessary, albeit ambitious, benchmark that likely will become an important goal in MS care, said Jaime Imitola, MD, Assistant Professor of Neurology and Neuroscience, and Michael K. Racke, MD, Professor and Chair of the Department of Neurology, both at Ohio State University in Columbus, in an accompanying editorial.

Although the study suggests that NEDA is difficult to maintain over the long term, the outcome has prognostic value at two years. “Neurologists must start discussing the goal of disease-activity-free status with their patients to take NEDA from the uniform environment of clinical trials to actual clinical practice,” said Drs. Imitola and Racke.

—Bianca Nogrady

For patients with multiple sclerosis (MS), having no evidence of disease activity (NEDA) at two years has a positive predictive value of 78.3% for absence of progression at seven years, according to research published in the February issue of JAMA Neurology.

Although 46% of patients in the study had achieved NEDA at one year, 7.9% of patients maintained NEDA after seven years. These findings result from a longitudinal study of 215 patients with clinically isolated syndrome or relapsing-remitting MS.

Dalia L. Rotstein, MD, Assistant Professor of Neurology at the University of Toronto, and her colleagues analyzed data for members of the Comprehensive Longitudinal Investigation of MS at Brigham and Women’s Hospital (CLIMB) cohort who had a minimum of seven years of prospective MRI and clinical follow-up data.

The concept of NEDA is common in the treatment of diseases such as cancer and rheumatoid arthritis, but is considered a secondary outcome measure in MS. NEDA is defined as the absence of new or enlarging T2 lesions or T1 gadolinium-enhancing lesions on MRI and the absence of sustained Expanded Disability Status Scale score progression or clinical relapse.

During the study period, clinical and MRI indicators of disease progress were dissociated, said the investigators. The percentage of patients who had no evidence of disease progression on one measure but not on another ranged from 42.9% at year 2 to 30.6% at year 7. No MRI disease activity occurred in 23.5% of patients at year 1 and in 14.8% of patients at year 7, but the percentage of participants who had NEDA was about 15% at both time points.

“Although NEDA has the potential to become not only a key outcome measure of disease-modifying therapy, but also a treat-to-target goal, it will require a comprehensive approach that integrates advances in MRI technology, linkage of blood and CSF biomarkers, and a high degree of cooperation among investigators,” said the authors.

The study did not explore the effects of different treatment approaches, but NEDA is a necessary, albeit ambitious, benchmark that likely will become an important goal in MS care, said Jaime Imitola, MD, Assistant Professor of Neurology and Neuroscience, and Michael K. Racke, MD, Professor and Chair of the Department of Neurology, both at Ohio State University in Columbus, in an accompanying editorial.

Although the study suggests that NEDA is difficult to maintain over the long term, the outcome has prognostic value at two years. “Neurologists must start discussing the goal of disease-activity-free status with their patients to take NEDA from the uniform environment of clinical trials to actual clinical practice,” said Drs. Imitola and Racke.

—Bianca Nogrady

For patients with multiple sclerosis (MS), having no evidence of disease activity (NEDA) at two years has a positive predictive value of 78.3% for absence of progression at seven years, according to research published in the February issue of JAMA Neurology.

Although 46% of patients in the study had achieved NEDA at one year, 7.9% of patients maintained NEDA after seven years. These findings result from a longitudinal study of 215 patients with clinically isolated syndrome or relapsing-remitting MS.

Dalia L. Rotstein, MD, Assistant Professor of Neurology at the University of Toronto, and her colleagues analyzed data for members of the Comprehensive Longitudinal Investigation of MS at Brigham and Women’s Hospital (CLIMB) cohort who had a minimum of seven years of prospective MRI and clinical follow-up data.

The concept of NEDA is common in the treatment of diseases such as cancer and rheumatoid arthritis, but is considered a secondary outcome measure in MS. NEDA is defined as the absence of new or enlarging T2 lesions or T1 gadolinium-enhancing lesions on MRI and the absence of sustained Expanded Disability Status Scale score progression or clinical relapse.

During the study period, clinical and MRI indicators of disease progress were dissociated, said the investigators. The percentage of patients who had no evidence of disease progression on one measure but not on another ranged from 42.9% at year 2 to 30.6% at year 7. No MRI disease activity occurred in 23.5% of patients at year 1 and in 14.8% of patients at year 7, but the percentage of participants who had NEDA was about 15% at both time points.

“Although NEDA has the potential to become not only a key outcome measure of disease-modifying therapy, but also a treat-to-target goal, it will require a comprehensive approach that integrates advances in MRI technology, linkage of blood and CSF biomarkers, and a high degree of cooperation among investigators,” said the authors.

The study did not explore the effects of different treatment approaches, but NEDA is a necessary, albeit ambitious, benchmark that likely will become an important goal in MS care, said Jaime Imitola, MD, Assistant Professor of Neurology and Neuroscience, and Michael K. Racke, MD, Professor and Chair of the Department of Neurology, both at Ohio State University in Columbus, in an accompanying editorial.

Although the study suggests that NEDA is difficult to maintain over the long term, the outcome has prognostic value at two years. “Neurologists must start discussing the goal of disease-activity-free status with their patients to take NEDA from the uniform environment of clinical trials to actual clinical practice,” said Drs. Imitola and Racke.

—Bianca Nogrady

Drinking more than two alcoholic beverages daily in middle age may raise a person’s stroke risk more than traditional factors such as high blood pressure and diabetes, according to new research published online ahead of print January 29 in Stroke. “Alcohol consumption should be considered an age-varying risk factor for stroke,” reported the study authors.

In a study of 11,644 middle-aged Swedish twins who were followed for 43 years, researchers compared the effects of heavy drinking, which they defined as an average of more than two drinks daily, to those of light drinking, defined as less than half a drink daily.

The study’s main findings included the following observations:

• Heavy drinkers had about a 34% higher risk of stroke, compared with light drinkers.
• Midlife heavy drinkers (ie, between ages 50 and 70) were likely to have a stroke five years earlier in life, irrespective of genetic and early-life factors.
• Heavy drinkers had increased stroke risk in midlife, compared with people with other well-known risk factors like high blood pressure and diabetes.
• At around age 75, blood pressure and diabetes appeared to become two of the main influences on having a stroke.

Past studies have shown that alcohol affects stroke risk, but this study is the first to pinpoint differences associated with age. “We now have a clearer picture about these risk factors, how they change with age, and how the influence of drinking alcohol shifts as we get older,” said lead author Pavla Kadlecová, MSc, a statistician at St. Anne’s University Hospital’s International Clinical Research Center in Brno, Czech Republic.

Researchers analyzed results from the Swedish Twin Registry of same-sex twins who answered questionnaires between 1967 and 1970. All twins were younger than 60 at the start of the study. By 2010, the registry yielded 43 years of follow-up, including data on hospital discharge and cause of death. Researchers then sorted the data based on occurrence of stroke and covariates such as baseline age, sex, cardiovascular diseases, diabetes mellitus, stress reactivity, depression, BMI, smoking, and exercise.

Almost 30% of participants had a stroke. Participants were categorized as nondrinkers or light, moderate, or heavy drinkers, based on the questionnaires. Among monozygotic twin pairs, siblings who had a stroke drank more than siblings who hadn’t had a stroke, suggesting that midlife drinking raises stroke risk regardless of genetics and early lifestyle.

The study findings provide evidence for the American Heart Association’s recommended limit of two drinks per day for men and one for women. That limit is equivalent to 8 oz of wine (ie, two drinks) for a man and 4 oz of wine (ie, one drink) for a woman. “For mid-aged adults, avoiding [consumption of] more than two drinks per day could be a way to prevent stroke in later productive age (about 60s),” Ms. Kadlecová said.

Drinking more than two alcoholic beverages daily in middle age may raise a person’s stroke risk more than traditional factors such as high blood pressure and diabetes, according to new research published online ahead of print January 29 in Stroke. “Alcohol consumption should be considered an age-varying risk factor for stroke,” reported the study authors.

In a study of 11,644 middle-aged Swedish twins who were followed for 43 years, researchers compared the effects of heavy drinking, which they defined as an average of more than two drinks daily, to those of light drinking, defined as less than half a drink daily.

The study’s main findings included the following observations:

• Heavy drinkers had about a 34% higher risk of stroke, compared with light drinkers.
• Midlife heavy drinkers (ie, between ages 50 and 70) were likely to have a stroke five years earlier in life, irrespective of genetic and early-life factors.
• Heavy drinkers had increased stroke risk in midlife, compared with people with other well-known risk factors like high blood pressure and diabetes.
• At around age 75, blood pressure and diabetes appeared to become two of the main influences on having a stroke.

Past studies have shown that alcohol affects stroke risk, but this study is the first to pinpoint differences associated with age. “We now have a clearer picture about these risk factors, how they change with age, and how the influence of drinking alcohol shifts as we get older,” said lead author Pavla Kadlecová, MSc, a statistician at St. Anne’s University Hospital’s International Clinical Research Center in Brno, Czech Republic.

Researchers analyzed results from the Swedish Twin Registry of same-sex twins who answered questionnaires between 1967 and 1970. All twins were younger than 60 at the start of the study. By 2010, the registry yielded 43 years of follow-up, including data on hospital discharge and cause of death. Researchers then sorted the data based on occurrence of stroke and covariates such as baseline age, sex, cardiovascular diseases, diabetes mellitus, stress reactivity, depression, BMI, smoking, and exercise.

Almost 30% of participants had a stroke. Participants were categorized as nondrinkers or light, moderate, or heavy drinkers, based on the questionnaires. Among monozygotic twin pairs, siblings who had a stroke drank more than siblings who hadn’t had a stroke, suggesting that midlife drinking raises stroke risk regardless of genetics and early lifestyle.

The study findings provide evidence for the American Heart Association’s recommended limit of two drinks per day for men and one for women. That limit is equivalent to 8 oz of wine (ie, two drinks) for a man and 4 oz of wine (ie, one drink) for a woman. “For mid-aged adults, avoiding [consumption of] more than two drinks per day could be a way to prevent stroke in later productive age (about 60s),” Ms. Kadlecová said.

Drinking more than two alcoholic beverages daily in middle age may raise a person’s stroke risk more than traditional factors such as high blood pressure and diabetes, according to new research published online ahead of print January 29 in Stroke. “Alcohol consumption should be considered an age-varying risk factor for stroke,” reported the study authors.

In a study of 11,644 middle-aged Swedish twins who were followed for 43 years, researchers compared the effects of heavy drinking, which they defined as an average of more than two drinks daily, to those of light drinking, defined as less than half a drink daily.

The study’s main findings included the following observations:

• Heavy drinkers had about a 34% higher risk of stroke, compared with light drinkers.
• Midlife heavy drinkers (ie, between ages 50 and 70) were likely to have a stroke five years earlier in life, irrespective of genetic and early-life factors.
• Heavy drinkers had increased stroke risk in midlife, compared with people with other well-known risk factors like high blood pressure and diabetes.
• At around age 75, blood pressure and diabetes appeared to become two of the main influences on having a stroke.

Past studies have shown that alcohol affects stroke risk, but this study is the first to pinpoint differences associated with age. “We now have a clearer picture about these risk factors, how they change with age, and how the influence of drinking alcohol shifts as we get older,” said lead author Pavla Kadlecová, MSc, a statistician at St. Anne’s University Hospital’s International Clinical Research Center in Brno, Czech Republic.

Researchers analyzed results from the Swedish Twin Registry of same-sex twins who answered questionnaires between 1967 and 1970. All twins were younger than 60 at the start of the study. By 2010, the registry yielded 43 years of follow-up, including data on hospital discharge and cause of death. Researchers then sorted the data based on occurrence of stroke and covariates such as baseline age, sex, cardiovascular diseases, diabetes mellitus, stress reactivity, depression, BMI, smoking, and exercise.

Almost 30% of participants had a stroke. Participants were categorized as nondrinkers or light, moderate, or heavy drinkers, based on the questionnaires. Among monozygotic twin pairs, siblings who had a stroke drank more than siblings who hadn’t had a stroke, suggesting that midlife drinking raises stroke risk regardless of genetics and early lifestyle.

The study findings provide evidence for the American Heart Association’s recommended limit of two drinks per day for men and one for women. That limit is equivalent to 8 oz of wine (ie, two drinks) for a man and 4 oz of wine (ie, one drink) for a woman. “For mid-aged adults, avoiding [consumption of] more than two drinks per day could be a way to prevent stroke in later productive age (about 60s),” Ms. Kadlecová said.

Adolescents now are sleeping less per night than they did 20 years ago, according to research published online ahead of print February 16 in Pediatrics. The largest declines in nightly sleep time for all adolescents occurred between 1991 and 1995 and between 1996 and 2000. Furthermore, adolescents’ perceptions of whether their sleep is adequate often do not agree with objective sleep measures or consensus recommendations.

“Although the underlying reasons for the decreases in hours of sleep are unknown, there has been speculation that increased Internet and social media use and pressures due to the heightened competitiveness of the college admissions process are adding to the problem,” said Katherine M. Keyes, PhD, Assistant Professor of Epidemiology at Columbia University in New York City. “Declines in self-reported adolescent sleep across the last 20 years are concerning and suggest that there is potentially a significant public health concern that warrants health education and literacy approaches.”

The data result from the yearly Monitoring the Future survey, in which a nationally representative sample of students in the 8th, 10th, and 12th grades report how often they get seven or more hours of sleep and how often they get less sleep than they should. Dr. Keyes and colleagues examined data for 272,077 adolescents from 1991 to 2012.

Age-period-cohort analyses indicated that sleep has consistently decreased, especially during the late 1990s and early 2000s. Female students, members of racial or ethnic minorities, and students of lower socioeconomic status were less likely to report regularly getting seven or more hours of sleep per night, compared with males, non-Hispanic Caucasians, and students of higher socioeconomic status, respectively. The disparity according to race has increased in recent time periods. Members of racial or ethnic minorities and adolescents of low socioeconomic status, however, were more likely to self-report adequate sleep, compared with Caucasians and adolescents of higher socioeconomic status.

The largest decrease in the percentage of respondents getting seven hours of sleep per night was among people age 15. In 1991, 72% of respondents in this age group reported regularly getting seven or more hours of sleep per night. In 2012, 63% of adolescents in this age group reported regularly getting seven or more hours of sleep per night.

The National Sleep Foundation recommends nine hours of sleep per night for adolescents. Inadequate sleep is associated with mental health problems, academic problems, substance abuse, and weight gain.

—Erik Greb

Adolescents now are sleeping less per night than they did 20 years ago, according to research published online ahead of print February 16 in Pediatrics. The largest declines in nightly sleep time for all adolescents occurred between 1991 and 1995 and between 1996 and 2000. Furthermore, adolescents’ perceptions of whether their sleep is adequate often do not agree with objective sleep measures or consensus recommendations.

“Although the underlying reasons for the decreases in hours of sleep are unknown, there has been speculation that increased Internet and social media use and pressures due to the heightened competitiveness of the college admissions process are adding to the problem,” said Katherine M. Keyes, PhD, Assistant Professor of Epidemiology at Columbia University in New York City. “Declines in self-reported adolescent sleep across the last 20 years are concerning and suggest that there is potentially a significant public health concern that warrants health education and literacy approaches.”

The data result from the yearly Monitoring the Future survey, in which a nationally representative sample of students in the 8th, 10th, and 12th grades report how often they get seven or more hours of sleep and how often they get less sleep than they should. Dr. Keyes and colleagues examined data for 272,077 adolescents from 1991 to 2012.

Age-period-cohort analyses indicated that sleep has consistently decreased, especially during the late 1990s and early 2000s. Female students, members of racial or ethnic minorities, and students of lower socioeconomic status were less likely to report regularly getting seven or more hours of sleep per night, compared with males, non-Hispanic Caucasians, and students of higher socioeconomic status, respectively. The disparity according to race has increased in recent time periods. Members of racial or ethnic minorities and adolescents of low socioeconomic status, however, were more likely to self-report adequate sleep, compared with Caucasians and adolescents of higher socioeconomic status.

The largest decrease in the percentage of respondents getting seven hours of sleep per night was among people age 15. In 1991, 72% of respondents in this age group reported regularly getting seven or more hours of sleep per night. In 2012, 63% of adolescents in this age group reported regularly getting seven or more hours of sleep per night.

The National Sleep Foundation recommends nine hours of sleep per night for adolescents. Inadequate sleep is associated with mental health problems, academic problems, substance abuse, and weight gain.

—Erik Greb

Adolescents now are sleeping less per night than they did 20 years ago, according to research published online ahead of print February 16 in Pediatrics. The largest declines in nightly sleep time for all adolescents occurred between 1991 and 1995 and between 1996 and 2000. Furthermore, adolescents’ perceptions of whether their sleep is adequate often do not agree with objective sleep measures or consensus recommendations.

“Although the underlying reasons for the decreases in hours of sleep are unknown, there has been speculation that increased Internet and social media use and pressures due to the heightened competitiveness of the college admissions process are adding to the problem,” said Katherine M. Keyes, PhD, Assistant Professor of Epidemiology at Columbia University in New York City. “Declines in self-reported adolescent sleep across the last 20 years are concerning and suggest that there is potentially a significant public health concern that warrants health education and literacy approaches.”

The data result from the yearly Monitoring the Future survey, in which a nationally representative sample of students in the 8th, 10th, and 12th grades report how often they get seven or more hours of sleep and how often they get less sleep than they should. Dr. Keyes and colleagues examined data for 272,077 adolescents from 1991 to 2012.

Age-period-cohort analyses indicated that sleep has consistently decreased, especially during the late 1990s and early 2000s. Female students, members of racial or ethnic minorities, and students of lower socioeconomic status were less likely to report regularly getting seven or more hours of sleep per night, compared with males, non-Hispanic Caucasians, and students of higher socioeconomic status, respectively. The disparity according to race has increased in recent time periods. Members of racial or ethnic minorities and adolescents of low socioeconomic status, however, were more likely to self-report adequate sleep, compared with Caucasians and adolescents of higher socioeconomic status.

The largest decrease in the percentage of respondents getting seven hours of sleep per night was among people age 15. In 1991, 72% of respondents in this age group reported regularly getting seven or more hours of sleep per night. In 2012, 63% of adolescents in this age group reported regularly getting seven or more hours of sleep per night.

The National Sleep Foundation recommends nine hours of sleep per night for adolescents. Inadequate sleep is associated with mental health problems, academic problems, substance abuse, and weight gain.

—Erik Greb

The use of electronic devices before bedtime and high screen usage during the day independently increase the likelihood of sleep deprivation among teenagers, according to a study published online ahead of print February 2 in BMJ Open.

“While the frequency of use differed between the various devices, the relation between different types of electronic devices and sleep remained significant,” said Mari Hysing, PsyD, a researcher at Uni Research Health in Bergen, Norway. “This [finding] suggests that the established relationship between TV and sleep found in previous studies can be generalized to newer technology.”

Dr. Hysing and her colleagues gathered data from 9,846 participants between ages 16 and 19 in Hordaland County, Norway. The researchers asked participants about their use of electronic devices (ie, personal computers, cellphones, MP3 players, tablets, video game consoles, and televisions) during daytime and nighttime. They also asked about participants’ sleep quantity and quality.

The investigators assessed whether the teenagers used any electronic devices in their bedrooms during the hour before they went to sleep, how often they used them during the daytime, and for what reasons they used the devices. The sleep data included typical bedtimes, rise times, time in bed, and total sleep on weekends and weekdays.

Nearly all teenagers used at least one, and often more than one, electronic device in the hour before bed. More than 80% reported using a computer, more than half reported watching TV, and approximately 90% of girls and 80% of boys reported using a cellphone.

Total daily daytime screen use averaged approximately 5.5 hours for girls and more than 6.5 hours for boys. Teenagers who used an electronic device in the hour before bed, used screens for more than four hours total per day, or used any electronic device for at least two hours per day were more likely to have a sleep deficiency of at least two hours per day.

Participants using a computer or a cellphone in the hour before bed were 52% and 48% more likely, respectively, to take more than 60 minutes to fall asleep. Before-bed computer or cellphone use increased the likelihood of a sleep deficit of at least two hours by 53% and 35%, respectively.

Teens were 2.7 times more likely to get less than five hours of sleep with computer use before bed and 1.85 times more likely to have this outcome with cellphone use before bed. Getting less than five hours of sleep was 3.6 times more likely with at least four hours of total daily screen time.

—Tara Haelle

The use of electronic devices before bedtime and high screen usage during the day independently increase the likelihood of sleep deprivation among teenagers, according to a study published online ahead of print February 2 in BMJ Open.

“While the frequency of use differed between the various devices, the relation between different types of electronic devices and sleep remained significant,” said Mari Hysing, PsyD, a researcher at Uni Research Health in Bergen, Norway. “This [finding] suggests that the established relationship between TV and sleep found in previous studies can be generalized to newer technology.”

Dr. Hysing and her colleagues gathered data from 9,846 participants between ages 16 and 19 in Hordaland County, Norway. The researchers asked participants about their use of electronic devices (ie, personal computers, cellphones, MP3 players, tablets, video game consoles, and televisions) during daytime and nighttime. They also asked about participants’ sleep quantity and quality.

The investigators assessed whether the teenagers used any electronic devices in their bedrooms during the hour before they went to sleep, how often they used them during the daytime, and for what reasons they used the devices. The sleep data included typical bedtimes, rise times, time in bed, and total sleep on weekends and weekdays.

Nearly all teenagers used at least one, and often more than one, electronic device in the hour before bed. More than 80% reported using a computer, more than half reported watching TV, and approximately 90% of girls and 80% of boys reported using a cellphone.

Total daily daytime screen use averaged approximately 5.5 hours for girls and more than 6.5 hours for boys. Teenagers who used an electronic device in the hour before bed, used screens for more than four hours total per day, or used any electronic device for at least two hours per day were more likely to have a sleep deficiency of at least two hours per day.

Participants using a computer or a cellphone in the hour before bed were 52% and 48% more likely, respectively, to take more than 60 minutes to fall asleep. Before-bed computer or cellphone use increased the likelihood of a sleep deficit of at least two hours by 53% and 35%, respectively.

Teens were 2.7 times more likely to get less than five hours of sleep with computer use before bed and 1.85 times more likely to have this outcome with cellphone use before bed. Getting less than five hours of sleep was 3.6 times more likely with at least four hours of total daily screen time.

—Tara Haelle

The use of electronic devices before bedtime and high screen usage during the day independently increase the likelihood of sleep deprivation among teenagers, according to a study published online ahead of print February 2 in BMJ Open.

“While the frequency of use differed between the various devices, the relation between different types of electronic devices and sleep remained significant,” said Mari Hysing, PsyD, a researcher at Uni Research Health in Bergen, Norway. “This [finding] suggests that the established relationship between TV and sleep found in previous studies can be generalized to newer technology.”

Dr. Hysing and her colleagues gathered data from 9,846 participants between ages 16 and 19 in Hordaland County, Norway. The researchers asked participants about their use of electronic devices (ie, personal computers, cellphones, MP3 players, tablets, video game consoles, and televisions) during daytime and nighttime. They also asked about participants’ sleep quantity and quality.

The investigators assessed whether the teenagers used any electronic devices in their bedrooms during the hour before they went to sleep, how often they used them during the daytime, and for what reasons they used the devices. The sleep data included typical bedtimes, rise times, time in bed, and total sleep on weekends and weekdays.

Nearly all teenagers used at least one, and often more than one, electronic device in the hour before bed. More than 80% reported using a computer, more than half reported watching TV, and approximately 90% of girls and 80% of boys reported using a cellphone.

Total daily daytime screen use averaged approximately 5.5 hours for girls and more than 6.5 hours for boys. Teenagers who used an electronic device in the hour before bed, used screens for more than four hours total per day, or used any electronic device for at least two hours per day were more likely to have a sleep deficiency of at least two hours per day.

Participants using a computer or a cellphone in the hour before bed were 52% and 48% more likely, respectively, to take more than 60 minutes to fall asleep. Before-bed computer or cellphone use increased the likelihood of a sleep deficit of at least two hours by 53% and 35%, respectively.

Teens were 2.7 times more likely to get less than five hours of sleep with computer use before bed and 1.85 times more likely to have this outcome with cellphone use before bed. Getting less than five hours of sleep was 3.6 times more likely with at least four hours of total daily screen time.

—Tara Haelle

Treatment with creatine monohydrate for at least five years, compared with placebo, did not improve clinical outcome in patients with early and treated Parkinson’s disease, according to a study in the February 10 issue of JAMA. “Creatine was initially considered because of evidence that it plays an important role in cellular energy production, which may be impaired in Parkinson’s disease,” the research team wrote. “Yet despite the available preclinical and clinical evidence, creatine failed to slow the clinical progression of Parkinson’s disease, as measured across five domains of Parkinson’s disease measured in the long-term clinical trial.”

To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in patients with Parkinson’s disease, Karl Kieburtz, MD, MPH, Senior Associate Dean of Clinical Research at the University of Rochester in New York, and colleagues conducted a long-term, multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1,741 men and women with early (ie, within five years of diagnosis) and treated (ie, receiving dopaminergic therapy) Parkinson’s disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.

Participants were randomized to receive placebo or creatine monohydrate (10 g/day) for a minimum of five years (maximum follow-up, eight years). The primary outcome measure was a difference in clinical decline from baseline to five-year follow-up, compared between the two groups using a global statistical test. Clinical status was defined by modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity.

The trial was terminated early for futility, based on the results of a planned interim analysis of participants enrolled at least five years prior to the date of the analysis (n = 955). The median follow-up time was four years. Using several measures of Parkinson’s disease progression, the researchers found that treatment with creatine, compared with placebo, did not improve clinical outcomes. Of the 955 participants, the means of the summed ranks were 2,360 for placebo and 2,414 for creatine. There were no detectable differences in adverse and serious adverse events by body system.

“These findings do not support the use of creatine monohydrate in patients with Parkinson’s disease,” the authors concluded.

—Glenn S. Williams

Treatment with creatine monohydrate for at least five years, compared with placebo, did not improve clinical outcome in patients with early and treated Parkinson’s disease, according to a study in the February 10 issue of JAMA. “Creatine was initially considered because of evidence that it plays an important role in cellular energy production, which may be impaired in Parkinson’s disease,” the research team wrote. “Yet despite the available preclinical and clinical evidence, creatine failed to slow the clinical progression of Parkinson’s disease, as measured across five domains of Parkinson’s disease measured in the long-term clinical trial.”

To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in patients with Parkinson’s disease, Karl Kieburtz, MD, MPH, Senior Associate Dean of Clinical Research at the University of Rochester in New York, and colleagues conducted a long-term, multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1,741 men and women with early (ie, within five years of diagnosis) and treated (ie, receiving dopaminergic therapy) Parkinson’s disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.

Participants were randomized to receive placebo or creatine monohydrate (10 g/day) for a minimum of five years (maximum follow-up, eight years). The primary outcome measure was a difference in clinical decline from baseline to five-year follow-up, compared between the two groups using a global statistical test. Clinical status was defined by modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity.

The trial was terminated early for futility, based on the results of a planned interim analysis of participants enrolled at least five years prior to the date of the analysis (n = 955). The median follow-up time was four years. Using several measures of Parkinson’s disease progression, the researchers found that treatment with creatine, compared with placebo, did not improve clinical outcomes. Of the 955 participants, the means of the summed ranks were 2,360 for placebo and 2,414 for creatine. There were no detectable differences in adverse and serious adverse events by body system.

“These findings do not support the use of creatine monohydrate in patients with Parkinson’s disease,” the authors concluded.

—Glenn S. Williams

Treatment with creatine monohydrate for at least five years, compared with placebo, did not improve clinical outcome in patients with early and treated Parkinson’s disease, according to a study in the February 10 issue of JAMA. “Creatine was initially considered because of evidence that it plays an important role in cellular energy production, which may be impaired in Parkinson’s disease,” the research team wrote. “Yet despite the available preclinical and clinical evidence, creatine failed to slow the clinical progression of Parkinson’s disease, as measured across five domains of Parkinson’s disease measured in the long-term clinical trial.”

To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in patients with Parkinson’s disease, Karl Kieburtz, MD, MPH, Senior Associate Dean of Clinical Research at the University of Rochester in New York, and colleagues conducted a long-term, multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1,741 men and women with early (ie, within five years of diagnosis) and treated (ie, receiving dopaminergic therapy) Parkinson’s disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.

Participants were randomized to receive placebo or creatine monohydrate (10 g/day) for a minimum of five years (maximum follow-up, eight years). The primary outcome measure was a difference in clinical decline from baseline to five-year follow-up, compared between the two groups using a global statistical test. Clinical status was defined by modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity.

The trial was terminated early for futility, based on the results of a planned interim analysis of participants enrolled at least five years prior to the date of the analysis (n = 955). The median follow-up time was four years. Using several measures of Parkinson’s disease progression, the researchers found that treatment with creatine, compared with placebo, did not improve clinical outcomes. Of the 955 participants, the means of the summed ranks were 2,360 for placebo and 2,414 for creatine. There were no detectable differences in adverse and serious adverse events by body system.

“These findings do not support the use of creatine monohydrate in patients with Parkinson’s disease,” the authors concluded.

—Glenn S. Williams

To improve the quality and lower the cost of care, guidelines recommend conservative treatment for most cases of headache, which accounts for more than 12 million visits to US clinicians and more than $31 billion in lost productivity and medical costs annually. Despite these guidelines, the treatment of headache has become less conservative. Fewer physicians are counseling patients on lifestyle modification, and advanced imaging (eg, CT and MRI) and referrals to specialists are increasing, according to the results of a study published online ahead of print January 8 in the Journal of General Internal Medicine.

Researchers from Beth Israel Deaconess Medical Center (BIDMC) in Boston identified 9,362 visits for headache using data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS). The data represent an estimated 144 million visits from 1999 through 2010. The researchers found substantial increases in the use of low-value, high-cost services. CT and MRI were ordered in 6.7% of visits from 1999 to 2000, compared with 13.9% of visits from 2009 to 2010. Requests for imaging increased more rapidly for patients who presented with acute symptoms rather than chronic headache. The rate of referrals rose from 6.9% to 13.2% of visits in the same time frame, even as patient counseling decreased from 23.5% to 18.5% of visits. Medication use also increased.

“The assessment of headache depends on identifying the relatively rare instances when serious underlying causes are suspected,” said lead author John N. Mafi, MD, a research fellow in general medicine at BIDMC. The researchers excluded cases with red flags such as neurologic signs and symptoms, cancer, head trauma, or seizures, from the study. Noting that evidence-based guidelines from the American Academy of Neurology, among other groups, call for counseling on lifestyle modification for routine headache, Dr. Mafi said he was “particularly alarmed about the overall trend of more imaging tests, medications, and referrals alongside less counseling.”

The use of prescription and over-the-counter nonsteroidal anti-inflammatory drugs and acetaminophen barely changed during the study period. The drugs were used in approximately 16% of visits over the course of the study, while use of triptans and ergot alkaloids increased from 9.8% during 1999–2000 to 15.4% of visits during 2009–2010. The use of recommended preventive therapies, including anticonvulsants, antidepressants, beta blockers, and calcium channel blockers increased from 8.5% of visits during 1999–2000 to 15.9% of visits during 2009–2010. The use of opioids and barbiturates, which is discouraged, remained at 18% of visits.

“These findings seem to reflect a larger trend in the US health care system beyond just headache,” Dr. Mafi observed, adding that “overhurried doctors seem to be spending less time connecting with their patients and more time ordering tests and treatments. This study suggests that the current 20-minute visit-based model of health care is broken and that we need to move toward promoting and reimbursing innovative solutions such as doctors and patients electronically collaborating on their health care outside the office visit.”

Senior author Bruce Landon, MD, MSc, a staff physician at BIDMC and Professor of Health Care Policy at Harvard Medical School, cited particular concern about the consequences of overuse of imaging, both in terms of cost and treatment. CT head or brain scans are “most frequently ordered inappropriately for chronic headache,” Dr. Landon said, adding that “incidental findings provoke unnecessary patient anxiety, can lead to more invasive procedures, and often require follow-up testing.”

—Helen Lippman

To improve the quality and lower the cost of care, guidelines recommend conservative treatment for most cases of headache, which accounts for more than 12 million visits to US clinicians and more than $31 billion in lost productivity and medical costs annually. Despite these guidelines, the treatment of headache has become less conservative. Fewer physicians are counseling patients on lifestyle modification, and advanced imaging (eg, CT and MRI) and referrals to specialists are increasing, according to the results of a study published online ahead of print January 8 in the Journal of General Internal Medicine.

Researchers from Beth Israel Deaconess Medical Center (BIDMC) in Boston identified 9,362 visits for headache using data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS). The data represent an estimated 144 million visits from 1999 through 2010. The researchers found substantial increases in the use of low-value, high-cost services. CT and MRI were ordered in 6.7% of visits from 1999 to 2000, compared with 13.9% of visits from 2009 to 2010. Requests for imaging increased more rapidly for patients who presented with acute symptoms rather than chronic headache. The rate of referrals rose from 6.9% to 13.2% of visits in the same time frame, even as patient counseling decreased from 23.5% to 18.5% of visits. Medication use also increased.

“The assessment of headache depends on identifying the relatively rare instances when serious underlying causes are suspected,” said lead author John N. Mafi, MD, a research fellow in general medicine at BIDMC. The researchers excluded cases with red flags such as neurologic signs and symptoms, cancer, head trauma, or seizures, from the study. Noting that evidence-based guidelines from the American Academy of Neurology, among other groups, call for counseling on lifestyle modification for routine headache, Dr. Mafi said he was “particularly alarmed about the overall trend of more imaging tests, medications, and referrals alongside less counseling.”

The use of prescription and over-the-counter nonsteroidal anti-inflammatory drugs and acetaminophen barely changed during the study period. The drugs were used in approximately 16% of visits over the course of the study, while use of triptans and ergot alkaloids increased from 9.8% during 1999–2000 to 15.4% of visits during 2009–2010. The use of recommended preventive therapies, including anticonvulsants, antidepressants, beta blockers, and calcium channel blockers increased from 8.5% of visits during 1999–2000 to 15.9% of visits during 2009–2010. The use of opioids and barbiturates, which is discouraged, remained at 18% of visits.

“These findings seem to reflect a larger trend in the US health care system beyond just headache,” Dr. Mafi observed, adding that “overhurried doctors seem to be spending less time connecting with their patients and more time ordering tests and treatments. This study suggests that the current 20-minute visit-based model of health care is broken and that we need to move toward promoting and reimbursing innovative solutions such as doctors and patients electronically collaborating on their health care outside the office visit.”

Senior author Bruce Landon, MD, MSc, a staff physician at BIDMC and Professor of Health Care Policy at Harvard Medical School, cited particular concern about the consequences of overuse of imaging, both in terms of cost and treatment. CT head or brain scans are “most frequently ordered inappropriately for chronic headache,” Dr. Landon said, adding that “incidental findings provoke unnecessary patient anxiety, can lead to more invasive procedures, and often require follow-up testing.”

—Helen Lippman

To improve the quality and lower the cost of care, guidelines recommend conservative treatment for most cases of headache, which accounts for more than 12 million visits to US clinicians and more than $31 billion in lost productivity and medical costs annually. Despite these guidelines, the treatment of headache has become less conservative. Fewer physicians are counseling patients on lifestyle modification, and advanced imaging (eg, CT and MRI) and referrals to specialists are increasing, according to the results of a study published online ahead of print January 8 in the Journal of General Internal Medicine.

Researchers from Beth Israel Deaconess Medical Center (BIDMC) in Boston identified 9,362 visits for headache using data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS). The data represent an estimated 144 million visits from 1999 through 2010. The researchers found substantial increases in the use of low-value, high-cost services. CT and MRI were ordered in 6.7% of visits from 1999 to 2000, compared with 13.9% of visits from 2009 to 2010. Requests for imaging increased more rapidly for patients who presented with acute symptoms rather than chronic headache. The rate of referrals rose from 6.9% to 13.2% of visits in the same time frame, even as patient counseling decreased from 23.5% to 18.5% of visits. Medication use also increased.

“The assessment of headache depends on identifying the relatively rare instances when serious underlying causes are suspected,” said lead author John N. Mafi, MD, a research fellow in general medicine at BIDMC. The researchers excluded cases with red flags such as neurologic signs and symptoms, cancer, head trauma, or seizures, from the study. Noting that evidence-based guidelines from the American Academy of Neurology, among other groups, call for counseling on lifestyle modification for routine headache, Dr. Mafi said he was “particularly alarmed about the overall trend of more imaging tests, medications, and referrals alongside less counseling.”

The use of prescription and over-the-counter nonsteroidal anti-inflammatory drugs and acetaminophen barely changed during the study period. The drugs were used in approximately 16% of visits over the course of the study, while use of triptans and ergot alkaloids increased from 9.8% during 1999–2000 to 15.4% of visits during 2009–2010. The use of recommended preventive therapies, including anticonvulsants, antidepressants, beta blockers, and calcium channel blockers increased from 8.5% of visits during 1999–2000 to 15.9% of visits during 2009–2010. The use of opioids and barbiturates, which is discouraged, remained at 18% of visits.

“These findings seem to reflect a larger trend in the US health care system beyond just headache,” Dr. Mafi observed, adding that “overhurried doctors seem to be spending less time connecting with their patients and more time ordering tests and treatments. This study suggests that the current 20-minute visit-based model of health care is broken and that we need to move toward promoting and reimbursing innovative solutions such as doctors and patients electronically collaborating on their health care outside the office visit.”

Senior author Bruce Landon, MD, MSc, a staff physician at BIDMC and Professor of Health Care Policy at Harvard Medical School, cited particular concern about the consequences of overuse of imaging, both in terms of cost and treatment. CT head or brain scans are “most frequently ordered inappropriately for chronic headache,” Dr. Landon said, adding that “incidental findings provoke unnecessary patient anxiety, can lead to more invasive procedures, and often require follow-up testing.”

—Helen Lippman

Rapid endovascular treatment appears to reduce mortality and improve functional outcomes among patients with acute ischemic stroke, according to data published online ahead of print in the New England Journal of Medicine. The study is known as Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE).

The research, along with the EXTEND-IA and MR CLEAN trials, provides additional evidence that endovascular treatment is effective for patients with ischemic stroke. These studies follow three stroke trials completed in 2013 that failed to show a benefit of endovascular therapy.

Patients Had a Small Infarct Core
Michael D. Hill, MD, Professor of Neurology at the University of Calgary in Canada, and colleagues designed an open-label trial with blinded outcome evaluation to analyze the effects of rapid endovascular treatment plus standard care. The researchers randomized patients with acute ischemic stroke to receive t-PA alone or t-PA plus endovascular treatment with available thrombectomy devices. Eligible participants had a small infarct core, an occluded proximal artery in the anterior circulation, and moderate to good collateral circulation. A small infarct core was defined as an Alberta Stroke Program Early CT score (ASPECTS) of 6 to 10. The investigators excluded patients with a proximal intracranial occlusion in the anterior circulation from the study if they presented at more than 12 hours after symptom onset. The trial’s primary outcome was the score on the modified Rankin Scale (mRS) at 90 days.

A total of 316 patients were randomized at 22 sites in Canada, the United States, the United Kingdom, Europe, and South Korea. After the publication of the MR CLEAN results, the data and safety monitoring board conducted an unplanned interim analysis of the data. The analysis indicated that the ESCAPE study had crossed a prespecified boundary for efficacy, and the board recommended that the study be halted.

Endovascular Treatment Reduced Disability
In all, 120 participants received t-PA and endovascular treatment, and 118 participants received t-PA alone. The average age of the population was approximately 70, and about 52% of participants were female. Median NIH Stroke Scale (NIHSS) score was 16 for the intervention group and 17 for the control group.

The median 90-day mRS score was 2 among patients who received endovascular treatment and 4 among patients who received t-PA alone. The proportion of patients with an mRS score of 0 to 2 at 90 days was 53.0% in the intervention group and 29.3% in the control group.

The mortality rate at 90 days among patients who received endovascular treatment was 10.4%, compared with 19.0% for patients who received t-PA alone. In addition, the rate of symptomatic intracerebral hemorrhage was 3.6% in the intervention group and 2.7% in the control group.

The researchers found no evidence of heterogeneity of treatment effect according to the presence or absence of cervical carotid occlusion or across any of the prespecified subgroups, which were defined by age, sex, baseline NIHSS score, baseline ASPECTS, occlusion location, and t-PA treatment status. All outcome variables showed a direction of effect in favor of the intervention.

Investigators used retrievable stents in 130 of the 151 participants (86.1%) who underwent an endovascular procedure, and 100 of these participants (77.0%) received a Solitaire stent manufactured by Covidien. In the intervention group, the median time from symptom onset to first reperfusion was 241 minutes, the median time from study CT to first reperfusion was 84 minutes, and the median time from groin puncture to first reperfusion was 30 minutes. Successful reperfusion occurred in 113 of 156 participants (72.4%) in the intervention group, including 79 of 112 participants who received IV t-PA and 34 of 44 participants who did not.

Eighteen patients in the intervention group had device-related or procedural complications. Serious adverse events in this group included hematoma at access site (three patients) and perforation of the middle cerebral artery (one patient). Fourteen patients in this group had adverse events that were not serious.

Endovascular Therapy Provides Benefits
“The trial confirms the benefit of endovascular treatment reported recently in the MR CLEAN trial,” said Dr. Hill. The study results could encourage a significant change in the treatment of acute ischemic stroke around the world, he added.

Post hoc analysis of previous studies of endovascular treatment indicated that achieving faster reperfusion was associated with a better clinical outcome, compared with slower reperfusion. “The ESCAPE trial achieved shorter interval times than those seen in past trials,” said Dr. Hill. “Critical to the achievement of rapid treatment was parallel decision making and action.

One limitation of the study is that most participants were enrolled at endovascular centers that could implement efficient workflow and imaging processes. “This level of efficiency and expertise is not currently widespread, which limits the immediate generalizability of our results,” said Dr. Hill.

“Key reasons for the success of the trial were, firstly, selecting appropriate patients using novel imaging technology; secondly, better organization and workflow to expedite treatment; and thirdly, use of modern technology to open the blood vessels,” said Mayank Goyal, MD, Professor of Radiology and Clinical Neurosciences at the University of Calgary and one of the investigators. The ESCAPE trial also had a lower rate of general anesthesia and a higher rate of successful reperfusion, compared with previous trials of endovascular treatment for stroke. “We believe that with the combined results from this trial and other trials, this [treatment] will become the standard of care.”

—Erik Greb

Rapid endovascular treatment appears to reduce mortality and improve functional outcomes among patients with acute ischemic stroke, according to data published online ahead of print in the New England Journal of Medicine. The study is known as Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE).

The research, along with the EXTEND-IA and MR CLEAN trials, provides additional evidence that endovascular treatment is effective for patients with ischemic stroke. These studies follow three stroke trials completed in 2013 that failed to show a benefit of endovascular therapy.

Patients Had a Small Infarct Core
Michael D. Hill, MD, Professor of Neurology at the University of Calgary in Canada, and colleagues designed an open-label trial with blinded outcome evaluation to analyze the effects of rapid endovascular treatment plus standard care. The researchers randomized patients with acute ischemic stroke to receive t-PA alone or t-PA plus endovascular treatment with available thrombectomy devices. Eligible participants had a small infarct core, an occluded proximal artery in the anterior circulation, and moderate to good collateral circulation. A small infarct core was defined as an Alberta Stroke Program Early CT score (ASPECTS) of 6 to 10. The investigators excluded patients with a proximal intracranial occlusion in the anterior circulation from the study if they presented at more than 12 hours after symptom onset. The trial’s primary outcome was the score on the modified Rankin Scale (mRS) at 90 days.

A total of 316 patients were randomized at 22 sites in Canada, the United States, the United Kingdom, Europe, and South Korea. After the publication of the MR CLEAN results, the data and safety monitoring board conducted an unplanned interim analysis of the data. The analysis indicated that the ESCAPE study had crossed a prespecified boundary for efficacy, and the board recommended that the study be halted.

Endovascular Treatment Reduced Disability
In all, 120 participants received t-PA and endovascular treatment, and 118 participants received t-PA alone. The average age of the population was approximately 70, and about 52% of participants were female. Median NIH Stroke Scale (NIHSS) score was 16 for the intervention group and 17 for the control group.

The median 90-day mRS score was 2 among patients who received endovascular treatment and 4 among patients who received t-PA alone. The proportion of patients with an mRS score of 0 to 2 at 90 days was 53.0% in the intervention group and 29.3% in the control group.

The mortality rate at 90 days among patients who received endovascular treatment was 10.4%, compared with 19.0% for patients who received t-PA alone. In addition, the rate of symptomatic intracerebral hemorrhage was 3.6% in the intervention group and 2.7% in the control group.

The researchers found no evidence of heterogeneity of treatment effect according to the presence or absence of cervical carotid occlusion or across any of the prespecified subgroups, which were defined by age, sex, baseline NIHSS score, baseline ASPECTS, occlusion location, and t-PA treatment status. All outcome variables showed a direction of effect in favor of the intervention.

Investigators used retrievable stents in 130 of the 151 participants (86.1%) who underwent an endovascular procedure, and 100 of these participants (77.0%) received a Solitaire stent manufactured by Covidien. In the intervention group, the median time from symptom onset to first reperfusion was 241 minutes, the median time from study CT to first reperfusion was 84 minutes, and the median time from groin puncture to first reperfusion was 30 minutes. Successful reperfusion occurred in 113 of 156 participants (72.4%) in the intervention group, including 79 of 112 participants who received IV t-PA and 34 of 44 participants who did not.

Eighteen patients in the intervention group had device-related or procedural complications. Serious adverse events in this group included hematoma at access site (three patients) and perforation of the middle cerebral artery (one patient). Fourteen patients in this group had adverse events that were not serious.

Endovascular Therapy Provides Benefits
“The trial confirms the benefit of endovascular treatment reported recently in the MR CLEAN trial,” said Dr. Hill. The study results could encourage a significant change in the treatment of acute ischemic stroke around the world, he added.

Post hoc analysis of previous studies of endovascular treatment indicated that achieving faster reperfusion was associated with a better clinical outcome, compared with slower reperfusion. “The ESCAPE trial achieved shorter interval times than those seen in past trials,” said Dr. Hill. “Critical to the achievement of rapid treatment was parallel decision making and action.

One limitation of the study is that most participants were enrolled at endovascular centers that could implement efficient workflow and imaging processes. “This level of efficiency and expertise is not currently widespread, which limits the immediate generalizability of our results,” said Dr. Hill.

“Key reasons for the success of the trial were, firstly, selecting appropriate patients using novel imaging technology; secondly, better organization and workflow to expedite treatment; and thirdly, use of modern technology to open the blood vessels,” said Mayank Goyal, MD, Professor of Radiology and Clinical Neurosciences at the University of Calgary and one of the investigators. The ESCAPE trial also had a lower rate of general anesthesia and a higher rate of successful reperfusion, compared with previous trials of endovascular treatment for stroke. “We believe that with the combined results from this trial and other trials, this [treatment] will become the standard of care.”

—Erik Greb

Rapid endovascular treatment appears to reduce mortality and improve functional outcomes among patients with acute ischemic stroke, according to data published online ahead of print in the New England Journal of Medicine. The study is known as Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times (ESCAPE).

The research, along with the EXTEND-IA and MR CLEAN trials, provides additional evidence that endovascular treatment is effective for patients with ischemic stroke. These studies follow three stroke trials completed in 2013 that failed to show a benefit of endovascular therapy.

Patients Had a Small Infarct Core
Michael D. Hill, MD, Professor of Neurology at the University of Calgary in Canada, and colleagues designed an open-label trial with blinded outcome evaluation to analyze the effects of rapid endovascular treatment plus standard care. The researchers randomized patients with acute ischemic stroke to receive t-PA alone or t-PA plus endovascular treatment with available thrombectomy devices. Eligible participants had a small infarct core, an occluded proximal artery in the anterior circulation, and moderate to good collateral circulation. A small infarct core was defined as an Alberta Stroke Program Early CT score (ASPECTS) of 6 to 10. The investigators excluded patients with a proximal intracranial occlusion in the anterior circulation from the study if they presented at more than 12 hours after symptom onset. The trial’s primary outcome was the score on the modified Rankin Scale (mRS) at 90 days.

A total of 316 patients were randomized at 22 sites in Canada, the United States, the United Kingdom, Europe, and South Korea. After the publication of the MR CLEAN results, the data and safety monitoring board conducted an unplanned interim analysis of the data. The analysis indicated that the ESCAPE study had crossed a prespecified boundary for efficacy, and the board recommended that the study be halted.

Endovascular Treatment Reduced Disability
In all, 120 participants received t-PA and endovascular treatment, and 118 participants received t-PA alone. The average age of the population was approximately 70, and about 52% of participants were female. Median NIH Stroke Scale (NIHSS) score was 16 for the intervention group and 17 for the control group.

The median 90-day mRS score was 2 among patients who received endovascular treatment and 4 among patients who received t-PA alone. The proportion of patients with an mRS score of 0 to 2 at 90 days was 53.0% in the intervention group and 29.3% in the control group.

The mortality rate at 90 days among patients who received endovascular treatment was 10.4%, compared with 19.0% for patients who received t-PA alone. In addition, the rate of symptomatic intracerebral hemorrhage was 3.6% in the intervention group and 2.7% in the control group.

The researchers found no evidence of heterogeneity of treatment effect according to the presence or absence of cervical carotid occlusion or across any of the prespecified subgroups, which were defined by age, sex, baseline NIHSS score, baseline ASPECTS, occlusion location, and t-PA treatment status. All outcome variables showed a direction of effect in favor of the intervention.

Investigators used retrievable stents in 130 of the 151 participants (86.1%) who underwent an endovascular procedure, and 100 of these participants (77.0%) received a Solitaire stent manufactured by Covidien. In the intervention group, the median time from symptom onset to first reperfusion was 241 minutes, the median time from study CT to first reperfusion was 84 minutes, and the median time from groin puncture to first reperfusion was 30 minutes. Successful reperfusion occurred in 113 of 156 participants (72.4%) in the intervention group, including 79 of 112 participants who received IV t-PA and 34 of 44 participants who did not.

Eighteen patients in the intervention group had device-related or procedural complications. Serious adverse events in this group included hematoma at access site (three patients) and perforation of the middle cerebral artery (one patient). Fourteen patients in this group had adverse events that were not serious.

Endovascular Therapy Provides Benefits
“The trial confirms the benefit of endovascular treatment reported recently in the MR CLEAN trial,” said Dr. Hill. The study results could encourage a significant change in the treatment of acute ischemic stroke around the world, he added.

Post hoc analysis of previous studies of endovascular treatment indicated that achieving faster reperfusion was associated with a better clinical outcome, compared with slower reperfusion. “The ESCAPE trial achieved shorter interval times than those seen in past trials,” said Dr. Hill. “Critical to the achievement of rapid treatment was parallel decision making and action.

One limitation of the study is that most participants were enrolled at endovascular centers that could implement efficient workflow and imaging processes. “This level of efficiency and expertise is not currently widespread, which limits the immediate generalizability of our results,” said Dr. Hill.

“Key reasons for the success of the trial were, firstly, selecting appropriate patients using novel imaging technology; secondly, better organization and workflow to expedite treatment; and thirdly, use of modern technology to open the blood vessels,” said Mayank Goyal, MD, Professor of Radiology and Clinical Neurosciences at the University of Calgary and one of the investigators. The ESCAPE trial also had a lower rate of general anesthesia and a higher rate of successful reperfusion, compared with previous trials of endovascular treatment for stroke. “We believe that with the combined results from this trial and other trials, this [treatment] will become the standard of care.”

—Erik Greb

Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) is significantly superior to mitoxantrone in reducing MRI activity in patients with severe multiple sclerosis (MS), according to a study published online ahead of print February 11 in Neurology.

The study involved 21 people whose MS-related disability had increased during the previous year despite treatment with first-line MS drugs. Participants’ average age was 36, and their average disability level required them to use a cane or crutch to walk.

Giovanni L. Mancardi, MD, Director of the Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health at the University of Genoa, and colleagues conducted a multicenter, phase II trial. They enrolled patients with secondary progressive or relapsing-remitting MS who had a documented increase in the year prior to enrollment on the Expanded Disability Status Scale (EDSS) score and one or more gadolinium-enhancing areas.

The primary end point was the cumulative number of new T2 lesions in the four years following randomization. Secondary end points were the cumulative number of gadolinium-enhancing lesions, relapse rate, and disability progression. A total of 21 patients were randomized. Following immunosupression, 12 patients received mitoxantrone (20 mg every month for six months) and nine patients underwent AHSCT. Seventeen patients had postbaseline evaluable MRI scans.

Intense immunosuppression followed by AHSCT reduced by 79% the number of new T2 lesions, compared with mitoxantrone treatment (2.5 new T2 lesions vs eight new T2 lesions, respectively). AHSCT also reduced gadolinium-enhancing lesions. None of the people who received AHSCT had a new gadolinium-enhancing lesion during the study, while 56% of those taking mitoxantrone had at least one new lesion. Annualized relapse rate was also reduced, but no difference was seen in the progression of disability.

AHSCT “appears to reset the immune system,” said Dr. Mancardi, lead author of the study. “With these results, we can speculate that stem cell treatment may profoundly affect the course of the disease.

“More research is needed with larger numbers of patients who are randomized to receive either the stem cell transplant or an approved therapy, but it’s very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that is not responding well to standard treatments,” Dr. Mancardi said.

Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) is significantly superior to mitoxantrone in reducing MRI activity in patients with severe multiple sclerosis (MS), according to a study published online ahead of print February 11 in Neurology.

The study involved 21 people whose MS-related disability had increased during the previous year despite treatment with first-line MS drugs. Participants’ average age was 36, and their average disability level required them to use a cane or crutch to walk.

Giovanni L. Mancardi, MD, Director of the Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health at the University of Genoa, and colleagues conducted a multicenter, phase II trial. They enrolled patients with secondary progressive or relapsing-remitting MS who had a documented increase in the year prior to enrollment on the Expanded Disability Status Scale (EDSS) score and one or more gadolinium-enhancing areas.

The primary end point was the cumulative number of new T2 lesions in the four years following randomization. Secondary end points were the cumulative number of gadolinium-enhancing lesions, relapse rate, and disability progression. A total of 21 patients were randomized. Following immunosupression, 12 patients received mitoxantrone (20 mg every month for six months) and nine patients underwent AHSCT. Seventeen patients had postbaseline evaluable MRI scans.

Intense immunosuppression followed by AHSCT reduced by 79% the number of new T2 lesions, compared with mitoxantrone treatment (2.5 new T2 lesions vs eight new T2 lesions, respectively). AHSCT also reduced gadolinium-enhancing lesions. None of the people who received AHSCT had a new gadolinium-enhancing lesion during the study, while 56% of those taking mitoxantrone had at least one new lesion. Annualized relapse rate was also reduced, but no difference was seen in the progression of disability.

AHSCT “appears to reset the immune system,” said Dr. Mancardi, lead author of the study. “With these results, we can speculate that stem cell treatment may profoundly affect the course of the disease.

“More research is needed with larger numbers of patients who are randomized to receive either the stem cell transplant or an approved therapy, but it’s very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that is not responding well to standard treatments,” Dr. Mancardi said.

Intense immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) is significantly superior to mitoxantrone in reducing MRI activity in patients with severe multiple sclerosis (MS), according to a study published online ahead of print February 11 in Neurology.

The study involved 21 people whose MS-related disability had increased during the previous year despite treatment with first-line MS drugs. Participants’ average age was 36, and their average disability level required them to use a cane or crutch to walk.

Giovanni L. Mancardi, MD, Director of the Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health at the University of Genoa, and colleagues conducted a multicenter, phase II trial. They enrolled patients with secondary progressive or relapsing-remitting MS who had a documented increase in the year prior to enrollment on the Expanded Disability Status Scale (EDSS) score and one or more gadolinium-enhancing areas.

The primary end point was the cumulative number of new T2 lesions in the four years following randomization. Secondary end points were the cumulative number of gadolinium-enhancing lesions, relapse rate, and disability progression. A total of 21 patients were randomized. Following immunosupression, 12 patients received mitoxantrone (20 mg every month for six months) and nine patients underwent AHSCT. Seventeen patients had postbaseline evaluable MRI scans.

Intense immunosuppression followed by AHSCT reduced by 79% the number of new T2 lesions, compared with mitoxantrone treatment (2.5 new T2 lesions vs eight new T2 lesions, respectively). AHSCT also reduced gadolinium-enhancing lesions. None of the people who received AHSCT had a new gadolinium-enhancing lesion during the study, while 56% of those taking mitoxantrone had at least one new lesion. Annualized relapse rate was also reduced, but no difference was seen in the progression of disability.

AHSCT “appears to reset the immune system,” said Dr. Mancardi, lead author of the study. “With these results, we can speculate that stem cell treatment may profoundly affect the course of the disease.

“More research is needed with larger numbers of patients who are randomized to receive either the stem cell transplant or an approved therapy, but it’s very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that is not responding well to standard treatments,” Dr. Mancardi said.

Early endovascular thrombectomy after t-PA may improve reperfusion, early neurologic recovery, and functional outcome, compared with t-PA alone, for patients with ischemic stroke who have major arterial occlusion and salvageable tissue on CT perfusion imaging, according to a study published online ahead of print February 11 in the New England Journal of Medicine. The study is called the Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA) trial.

Three major stroke trials completed in 2013 did not support endovascular therapy for acute ischemic stroke. The recent MR CLEAN study, however, suggested that the therapy is safe and effective. The EXTEND-IA trial provides further evidence of the treatment’s potential benefits for patients with ischemic stroke.

Bruce Campbell, MD, a neurologist at Royal Melbourne Hospital in Australia, and colleagues randomized patients to t-PA and clot retrieval with the Solitaire FR device or t-PA alone. The dose of t-PA for all patients was 0.9 mg/kg, and the drug was administered less than 4.5 hours after stroke onset. Endovascular therapy was initiated within six hours of stroke onset. Eligible participants had occlusion of the internal carotid or middle cerebral artery, an ischemic core volume of less than 70 mL, and salvageable tissue on CT perfusion.

The trial’s primary outcomes were the proportion of the perfusion lesion reperfused at 24 hours on CT or MR perfusion imaging, and the proportion of patients with early neurologic improvement. Early neurologic improvement was defined as a reduction in NIH Stroke Scale (NIHSS) score of eight or more points, or as a score of 0 or 1, by day three. The study’s secondary outcome was ordinal analysis of modified Rankin Scale (mRS) score at 90 days.

The researchers intended to randomize 100 patients, but the data safety and monitoring committee stopped the trial after 70 patients had been randomized because of the study treatment’s overwhelming efficacy. The committee’s action followed a review of the trial that had been prompted by the publication of the results of the MR CLEAN study.

In all, 35 patients received t-PA and endovascular treatment, and 35 patients received t-PA alone. In the intervention group, mean age was 68.6, median NIHSS score was 17, and median time to recanalization was 259 min. In the control group, mean age was 70.2 and median NIHSS score was 13.

Participants who received endovascular treatment had greater median reperfusion at 24 hours than patients who received t-PA alone (100% vs 37%). Of those patients who received endovascular treatment, 80% had early neurologic improvement, compared with 37% of those who received t-PA alone. Approximately 71% of people who received endovascular treatment achieved functional independence (ie, mRS score of 0 to 2) at 90 days, compared with 40% of patients who received t-PA alone.

Symptomatic intracerebral hemorrhage occurred in no patients who received endovascular treatment and two patients who received t-PA alone. Complications of endovascular treatment included one wire perforation and one groin hematoma.

Together with the MR CLEAN study, the EXTEND-IA trial is a “game-changer” in the treatment of stroke, said Peter Mitchell, MD, Director of Neurointervention Service at the Royal Melbourne Hospital and a study investigator. “The patients treated in EXTEND-IA had even better outcomes than [those] in MR CLEAN,” he added. “The key differences were improved rates of opening the blocked blood vessel, earlier treatment, and the use of more advanced brain imaging to select patients most likely to benefit.

“The challenge now is to implement stent thrombectomy as a standard treatment for stroke,” Dr. Mitchell said.

—Erik Greb

Early endovascular thrombectomy after t-PA may improve reperfusion, early neurologic recovery, and functional outcome, compared with t-PA alone, for patients with ischemic stroke who have major arterial occlusion and salvageable tissue on CT perfusion imaging, according to a study published online ahead of print February 11 in the New England Journal of Medicine. The study is called the Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA) trial.

Three major stroke trials completed in 2013 did not support endovascular therapy for acute ischemic stroke. The recent MR CLEAN study, however, suggested that the therapy is safe and effective. The EXTEND-IA trial provides further evidence of the treatment’s potential benefits for patients with ischemic stroke.

Bruce Campbell, MD, a neurologist at Royal Melbourne Hospital in Australia, and colleagues randomized patients to t-PA and clot retrieval with the Solitaire FR device or t-PA alone. The dose of t-PA for all patients was 0.9 mg/kg, and the drug was administered less than 4.5 hours after stroke onset. Endovascular therapy was initiated within six hours of stroke onset. Eligible participants had occlusion of the internal carotid or middle cerebral artery, an ischemic core volume of less than 70 mL, and salvageable tissue on CT perfusion.

The trial’s primary outcomes were the proportion of the perfusion lesion reperfused at 24 hours on CT or MR perfusion imaging, and the proportion of patients with early neurologic improvement. Early neurologic improvement was defined as a reduction in NIH Stroke Scale (NIHSS) score of eight or more points, or as a score of 0 or 1, by day three. The study’s secondary outcome was ordinal analysis of modified Rankin Scale (mRS) score at 90 days.

The researchers intended to randomize 100 patients, but the data safety and monitoring committee stopped the trial after 70 patients had been randomized because of the study treatment’s overwhelming efficacy. The committee’s action followed a review of the trial that had been prompted by the publication of the results of the MR CLEAN study.

In all, 35 patients received t-PA and endovascular treatment, and 35 patients received t-PA alone. In the intervention group, mean age was 68.6, median NIHSS score was 17, and median time to recanalization was 259 min. In the control group, mean age was 70.2 and median NIHSS score was 13.

Participants who received endovascular treatment had greater median reperfusion at 24 hours than patients who received t-PA alone (100% vs 37%). Of those patients who received endovascular treatment, 80% had early neurologic improvement, compared with 37% of those who received t-PA alone. Approximately 71% of people who received endovascular treatment achieved functional independence (ie, mRS score of 0 to 2) at 90 days, compared with 40% of patients who received t-PA alone.

Symptomatic intracerebral hemorrhage occurred in no patients who received endovascular treatment and two patients who received t-PA alone. Complications of endovascular treatment included one wire perforation and one groin hematoma.

Together with the MR CLEAN study, the EXTEND-IA trial is a “game-changer” in the treatment of stroke, said Peter Mitchell, MD, Director of Neurointervention Service at the Royal Melbourne Hospital and a study investigator. “The patients treated in EXTEND-IA had even better outcomes than [those] in MR CLEAN,” he added. “The key differences were improved rates of opening the blocked blood vessel, earlier treatment, and the use of more advanced brain imaging to select patients most likely to benefit.

“The challenge now is to implement stent thrombectomy as a standard treatment for stroke,” Dr. Mitchell said.

—Erik Greb

Early endovascular thrombectomy after t-PA may improve reperfusion, early neurologic recovery, and functional outcome, compared with t-PA alone, for patients with ischemic stroke who have major arterial occlusion and salvageable tissue on CT perfusion imaging, according to a study published online ahead of print February 11 in the New England Journal of Medicine. The study is called the Extending the Time for Thrombolysis in Emergency Neurological Deficits—Intra-Arterial (EXTEND-IA) trial.

Three major stroke trials completed in 2013 did not support endovascular therapy for acute ischemic stroke. The recent MR CLEAN study, however, suggested that the therapy is safe and effective. The EXTEND-IA trial provides further evidence of the treatment’s potential benefits for patients with ischemic stroke.

Bruce Campbell, MD, a neurologist at Royal Melbourne Hospital in Australia, and colleagues randomized patients to t-PA and clot retrieval with the Solitaire FR device or t-PA alone. The dose of t-PA for all patients was 0.9 mg/kg, and the drug was administered less than 4.5 hours after stroke onset. Endovascular therapy was initiated within six hours of stroke onset. Eligible participants had occlusion of the internal carotid or middle cerebral artery, an ischemic core volume of less than 70 mL, and salvageable tissue on CT perfusion.

The trial’s primary outcomes were the proportion of the perfusion lesion reperfused at 24 hours on CT or MR perfusion imaging, and the proportion of patients with early neurologic improvement. Early neurologic improvement was defined as a reduction in NIH Stroke Scale (NIHSS) score of eight or more points, or as a score of 0 or 1, by day three. The study’s secondary outcome was ordinal analysis of modified Rankin Scale (mRS) score at 90 days.

The researchers intended to randomize 100 patients, but the data safety and monitoring committee stopped the trial after 70 patients had been randomized because of the study treatment’s overwhelming efficacy. The committee’s action followed a review of the trial that had been prompted by the publication of the results of the MR CLEAN study.

In all, 35 patients received t-PA and endovascular treatment, and 35 patients received t-PA alone. In the intervention group, mean age was 68.6, median NIHSS score was 17, and median time to recanalization was 259 min. In the control group, mean age was 70.2 and median NIHSS score was 13.

Participants who received endovascular treatment had greater median reperfusion at 24 hours than patients who received t-PA alone (100% vs 37%). Of those patients who received endovascular treatment, 80% had early neurologic improvement, compared with 37% of those who received t-PA alone. Approximately 71% of people who received endovascular treatment achieved functional independence (ie, mRS score of 0 to 2) at 90 days, compared with 40% of patients who received t-PA alone.

Symptomatic intracerebral hemorrhage occurred in no patients who received endovascular treatment and two patients who received t-PA alone. Complications of endovascular treatment included one wire perforation and one groin hematoma.

Together with the MR CLEAN study, the EXTEND-IA trial is a “game-changer” in the treatment of stroke, said Peter Mitchell, MD, Director of Neurointervention Service at the Royal Melbourne Hospital and a study investigator. “The patients treated in EXTEND-IA had even better outcomes than [those] in MR CLEAN,” he added. “The key differences were improved rates of opening the blocked blood vessel, earlier treatment, and the use of more advanced brain imaging to select patients most likely to benefit.

“The challenge now is to implement stent thrombectomy as a standard treatment for stroke,” Dr. Mitchell said.

—Erik Greb