Compared with the natural history of the disease, disease-modifying treatments for multiple sclerosis (MS) significantly reduce the risks of long-term disability worsening and evolution to secondary progressive MS (SPMS), according to research published in the October issue of Annals of Neurology. The data also suggest that patients who have no evidence of disease activity (NEDA) for two years are no more likely to have long-term stability than patients who do not reach this end point.

“These observations challenge the concept that NEDA represents remission. Although NEDA may be a useful measure for assessing relative therapeutic efficacy, many patients who meet NEDA criteria over two years go on to develop clinically significant disability,” said Bruce A. C. Cree, MD, PhD, Associate Professor of Neurology at the University of California, San Francisco School of Medicine. “Worsening in patients who meet the two-year NEDA end point could result from active spinal cord disease not captured with brain MRI, progressive axonal or neuronal degeneration, or an escape from a true but transient remission state.

Researchers had anticipated that between 36% and 50% of patients with relapsing MS (RMS) would develop SPMS, but 11.3% of the cohort transitioned to SPMS during the course of the study. Evolution of sustained disability was also slower than expected, said Dr. Cree.

Examining Long-Term Effects of Treatment

Natural history studies from the pretreatment era suggest that between one-third and one-half of patients with MS experience substantial worsening of neurologic disability approximately 15 years after disease onset. Disease-modifying therapies in MS have been studied during the past two decades and are associated with improvement in the short term. Their effect on long-term outcomes is unknown, however. Furthermore, little is known about the relationship between short-term MRI measurements and long-term disability in MS.

As a result, Dr. Cree and colleagues conducted a prospective study to characterize the accrual of long-term disability in a cohort of actively treated patients with MS. Additionally, they sought to assess whether clinical and MRI data used in clinical trials have long-term prognostic value.

Eligible participants had all clinical subtypes of MS and were first evaluated at the MS Center at the University of California, San Francisco between July 2004 and September 2005. Patients were excluded if they were unable to tolerate MRI scans, had poor venous access, or if they had other significant medical illnesses that might interfere with goals of the study. Investigators followed participants annually for five years. In addition, patients underwent re-evaluation at extended time points for as long as 10 years after baseline.

Researchers defined disability progression as a clinically significant worsening in the Expanded Disability Status Scale (EDSS), the timed 25-foot walk, the nine-hole peg test, and the paced serial auditory addition test.

Two Tiers of Therapy

Participants were treated with FDA-approved therapies or off-label therapies. Researchers defined two treatment tiers and categorized therapies based on their relative perceived effectiveness using data from clinical trials.

The first tier of treatment, platform therapy, included interferon (IFN) beta, glatiramer acetate, and off-label therapies such as glucocorticoids, azathioprine, and mycophenolate mofetil. The second tier of treatment, high-potency therapy, included natalizumab, rituximab, mitoxantrone, and cyclophosphamide.

NEDA and Long-Term Disability

Of 517 actively managed patients with MS enrolled in the study, 366 had RMS, 48 had SPMS, 21 had primary progressive MS (PPMS), and 82 had clinically isolated syndrome (CIS). After 10 years of follow-up, neurologic disability was stable or improved, compared with baseline, in 41% of patients. Serum vitamin D levels were inversely associated with short-term MS disease activity, but were not associated with long-term disability. At a median time of 16.8 years after disease onset, 10.7% of patients reached an EDSS score of greater than or equal to 6, and 18.1% of patients evolved from RMS to SPMS.

The investigators concluded that evolution to SPMS in this study was significantly lower than expected, based on natural history studies. They also noted that short-term increases in EDSS did not necessarily predict future accumulation of long-term disability in patients with RMS. In addition, subjects with NEDA by clinical and MRI criteria during the first two years had long-term outcomes that were no different from those of the cohort as a whole.

“Treating to target with two-year NEDA as the goal may not result in protection against long-term disability,” said Dr. Cree. “Long-term studies are urgently needed to determine if high-intensity therapy, initiated at the time of diagnosis or used in patients with seemingly inactive disease, is superior to the escalation approach employed in this cohort.”

—Erica Tricarico

Suggested Reading

University of California, San Francisco MS-EPIC Team, Cree BA, Gourraud PA, et al. Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol. 2016;80(4):499-510.

Compared with the natural history of the disease, disease-modifying treatments for multiple sclerosis (MS) significantly reduce the risks of long-term disability worsening and evolution to secondary progressive MS (SPMS), according to research published in the October issue of Annals of Neurology. The data also suggest that patients who have no evidence of disease activity (NEDA) for two years are no more likely to have long-term stability than patients who do not reach this end point.

“These observations challenge the concept that NEDA represents remission. Although NEDA may be a useful measure for assessing relative therapeutic efficacy, many patients who meet NEDA criteria over two years go on to develop clinically significant disability,” said Bruce A. C. Cree, MD, PhD, Associate Professor of Neurology at the University of California, San Francisco School of Medicine. “Worsening in patients who meet the two-year NEDA end point could result from active spinal cord disease not captured with brain MRI, progressive axonal or neuronal degeneration, or an escape from a true but transient remission state.

Researchers had anticipated that between 36% and 50% of patients with relapsing MS (RMS) would develop SPMS, but 11.3% of the cohort transitioned to SPMS during the course of the study. Evolution of sustained disability was also slower than expected, said Dr. Cree.

Examining Long-Term Effects of Treatment

Natural history studies from the pretreatment era suggest that between one-third and one-half of patients with MS experience substantial worsening of neurologic disability approximately 15 years after disease onset. Disease-modifying therapies in MS have been studied during the past two decades and are associated with improvement in the short term. Their effect on long-term outcomes is unknown, however. Furthermore, little is known about the relationship between short-term MRI measurements and long-term disability in MS.

As a result, Dr. Cree and colleagues conducted a prospective study to characterize the accrual of long-term disability in a cohort of actively treated patients with MS. Additionally, they sought to assess whether clinical and MRI data used in clinical trials have long-term prognostic value.

Eligible participants had all clinical subtypes of MS and were first evaluated at the MS Center at the University of California, San Francisco between July 2004 and September 2005. Patients were excluded if they were unable to tolerate MRI scans, had poor venous access, or if they had other significant medical illnesses that might interfere with goals of the study. Investigators followed participants annually for five years. In addition, patients underwent re-evaluation at extended time points for as long as 10 years after baseline.

Researchers defined disability progression as a clinically significant worsening in the Expanded Disability Status Scale (EDSS), the timed 25-foot walk, the nine-hole peg test, and the paced serial auditory addition test.

Two Tiers of Therapy

Participants were treated with FDA-approved therapies or off-label therapies. Researchers defined two treatment tiers and categorized therapies based on their relative perceived effectiveness using data from clinical trials.

The first tier of treatment, platform therapy, included interferon (IFN) beta, glatiramer acetate, and off-label therapies such as glucocorticoids, azathioprine, and mycophenolate mofetil. The second tier of treatment, high-potency therapy, included natalizumab, rituximab, mitoxantrone, and cyclophosphamide.

NEDA and Long-Term Disability

Of 517 actively managed patients with MS enrolled in the study, 366 had RMS, 48 had SPMS, 21 had primary progressive MS (PPMS), and 82 had clinically isolated syndrome (CIS). After 10 years of follow-up, neurologic disability was stable or improved, compared with baseline, in 41% of patients. Serum vitamin D levels were inversely associated with short-term MS disease activity, but were not associated with long-term disability. At a median time of 16.8 years after disease onset, 10.7% of patients reached an EDSS score of greater than or equal to 6, and 18.1% of patients evolved from RMS to SPMS.

The investigators concluded that evolution to SPMS in this study was significantly lower than expected, based on natural history studies. They also noted that short-term increases in EDSS did not necessarily predict future accumulation of long-term disability in patients with RMS. In addition, subjects with NEDA by clinical and MRI criteria during the first two years had long-term outcomes that were no different from those of the cohort as a whole.

“Treating to target with two-year NEDA as the goal may not result in protection against long-term disability,” said Dr. Cree. “Long-term studies are urgently needed to determine if high-intensity therapy, initiated at the time of diagnosis or used in patients with seemingly inactive disease, is superior to the escalation approach employed in this cohort.”

—Erica Tricarico

Suggested Reading

University of California, San Francisco MS-EPIC Team, Cree BA, Gourraud PA, et al. Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol. 2016;80(4):499-510.

Compared with the natural history of the disease, disease-modifying treatments for multiple sclerosis (MS) significantly reduce the risks of long-term disability worsening and evolution to secondary progressive MS (SPMS), according to research published in the October issue of Annals of Neurology. The data also suggest that patients who have no evidence of disease activity (NEDA) for two years are no more likely to have long-term stability than patients who do not reach this end point.

“These observations challenge the concept that NEDA represents remission. Although NEDA may be a useful measure for assessing relative therapeutic efficacy, many patients who meet NEDA criteria over two years go on to develop clinically significant disability,” said Bruce A. C. Cree, MD, PhD, Associate Professor of Neurology at the University of California, San Francisco School of Medicine. “Worsening in patients who meet the two-year NEDA end point could result from active spinal cord disease not captured with brain MRI, progressive axonal or neuronal degeneration, or an escape from a true but transient remission state.

Researchers had anticipated that between 36% and 50% of patients with relapsing MS (RMS) would develop SPMS, but 11.3% of the cohort transitioned to SPMS during the course of the study. Evolution of sustained disability was also slower than expected, said Dr. Cree.

Examining Long-Term Effects of Treatment

Natural history studies from the pretreatment era suggest that between one-third and one-half of patients with MS experience substantial worsening of neurologic disability approximately 15 years after disease onset. Disease-modifying therapies in MS have been studied during the past two decades and are associated with improvement in the short term. Their effect on long-term outcomes is unknown, however. Furthermore, little is known about the relationship between short-term MRI measurements and long-term disability in MS.

As a result, Dr. Cree and colleagues conducted a prospective study to characterize the accrual of long-term disability in a cohort of actively treated patients with MS. Additionally, they sought to assess whether clinical and MRI data used in clinical trials have long-term prognostic value.

Eligible participants had all clinical subtypes of MS and were first evaluated at the MS Center at the University of California, San Francisco between July 2004 and September 2005. Patients were excluded if they were unable to tolerate MRI scans, had poor venous access, or if they had other significant medical illnesses that might interfere with goals of the study. Investigators followed participants annually for five years. In addition, patients underwent re-evaluation at extended time points for as long as 10 years after baseline.

Researchers defined disability progression as a clinically significant worsening in the Expanded Disability Status Scale (EDSS), the timed 25-foot walk, the nine-hole peg test, and the paced serial auditory addition test.

Two Tiers of Therapy

Participants were treated with FDA-approved therapies or off-label therapies. Researchers defined two treatment tiers and categorized therapies based on their relative perceived effectiveness using data from clinical trials.

The first tier of treatment, platform therapy, included interferon (IFN) beta, glatiramer acetate, and off-label therapies such as glucocorticoids, azathioprine, and mycophenolate mofetil. The second tier of treatment, high-potency therapy, included natalizumab, rituximab, mitoxantrone, and cyclophosphamide.

NEDA and Long-Term Disability

Of 517 actively managed patients with MS enrolled in the study, 366 had RMS, 48 had SPMS, 21 had primary progressive MS (PPMS), and 82 had clinically isolated syndrome (CIS). After 10 years of follow-up, neurologic disability was stable or improved, compared with baseline, in 41% of patients. Serum vitamin D levels were inversely associated with short-term MS disease activity, but were not associated with long-term disability. At a median time of 16.8 years after disease onset, 10.7% of patients reached an EDSS score of greater than or equal to 6, and 18.1% of patients evolved from RMS to SPMS.

The investigators concluded that evolution to SPMS in this study was significantly lower than expected, based on natural history studies. They also noted that short-term increases in EDSS did not necessarily predict future accumulation of long-term disability in patients with RMS. In addition, subjects with NEDA by clinical and MRI criteria during the first two years had long-term outcomes that were no different from those of the cohort as a whole.

“Treating to target with two-year NEDA as the goal may not result in protection against long-term disability,” said Dr. Cree. “Long-term studies are urgently needed to determine if high-intensity therapy, initiated at the time of diagnosis or used in patients with seemingly inactive disease, is superior to the escalation approach employed in this cohort.”

—Erica Tricarico

Suggested Reading

University of California, San Francisco MS-EPIC Team, Cree BA, Gourraud PA, et al. Long-term evolution of multiple sclerosis disability in the treatment era. Ann Neurol. 2016;80(4):499-510.

Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.

 
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.  

 
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.  

 
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.

 
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.

 
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.  

 
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.

Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.  

 
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE  ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE  ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.

 
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.

 
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.

People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.

—Kimberly Williams

Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.

 
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.  

 
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.  

 
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.

 
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.

 
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.  

 
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.

Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.  

 
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE  ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE  ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.

 
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.

 
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.

People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.

—Kimberly Williams

Concussions may accelerate Alzheimer's disease-related brain atrophy and cognitive decline in people who are at genetic risk for the condition, according to a study published online ahead of print January 11 in Brain. A total of 160 Iraq and Afghanistan war veterans between the ages of 19 and 58, were included in this study. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness. The findings highlight the importance of documenting head injuries, as they may interact with genetic risk to produce negative long-term health consequences, according to the authors.

 
During pregnancy, Asian women with poor sleep quality or short nocturnal sleep duration exhibit abnormal glucose regulation, according to a study published online ahead of print November 14 in Sleep. In all, 686 women with a singleton pregnancy attended a clinic visit at 26 to 28 weeks of gestation, as part of the Growing Up in Singapore Towards healthy Outcomes mother-offspring cohort study. Self-reported sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index. Two hundred ninety-six women had poor sleep quality, and 77 women were categorized as short sleepers. One hundred thirty-one women were diagnosed with gestational diabetes mellitus. Poor sleep quality and short nocturnal sleep duration were independently associated with increased risk of gestational diabetes mellitus.  

 
Heightened activity in the amygdala is associated with a greater risk of heart disease and stroke, according to a study published online ahead of print January 12 in Lancet. Investigators followed 293 people age 30 or older without known cardiovascular disease or active cancer disorders, who underwent PET/CT scans between January 1, 2005, and December 31, 2008. Twenty-two people had a cardiovascular disease event during mean follow-up of 3.7 years. Amygdalar activity was associated with increased bone-marrow activity, arterial inflammation, and risk of cardiovascular disease events. In a cross-sectional study of 13 patients who underwent psychometric analysis, amygdalar activity was significantly associated with arterial inflammation, and perceived stress was associated with amygdalar activity, arterial inflammation, and C-reactive protein.  

 
Developing hypertension at an older age may protect against dementia, according to a study published online January 16 in Alzheimer's & Dementia. The study included participants from a population-based longitudinal study of people age 90 and older (The 90+ Study) who were survivors of the Leisure World Cohort Study. Researchers estimated hypertension onset age using patient-reported information. A total of 559 participants without dementia were followed every six months for up to 10 years. Two hundred twenty-four participants developed dementia during follow-up. Compared with participants without hypertension, participants whose hypertension onset age was between 80 and 89 had a lower dementia risk, and participants with an onset age of 90 and older had the lowest risk.

 
Living close to heavy traffic is associated with a higher incidence of dementia, but not Parkinson's disease or multiple sclerosis, according to a study published online ahead of print January 4 in Lancet. Researchers assembled two population-based cohorts that included adults who resided in Ontario, Canada. Between 2001 and 2012, researchers identified 243,611 incident cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of multiple sclerosis. Dementia risk decreased as people lived farther away from a main road. Overall, there was a 7% higher risk of dementia among people living within 50 meters of a main road, a 4% higher risk at 50 to 100 meters, and a 2% higher risk at 101 to 200 meters. There was no increase in risk in those living more than 200 meters away.

 
The US Preventive Services Task Force (USPSTF) recommends that all women who are planning to become or capable of becoming pregnant take a daily supplement containing 0.4 mg to 0.8 mg of folic acid, according to a recommendation statement published in the January 10 issue of JAMA. In 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation. The USPSTF evaluated one randomized clinical trial, two cohort studies, eight case-control studies, and two publications from the previous USPSTF review. The task force found no new substantial evidence about the benefits and harms of folic acid supplementation. The USPSTF reaffirmed its 2009 recommendation.  

 
Low serum 25-hydroxyvitamin D (25[OH]D] concentration is associated with markedly higher risk of frequent headache in men, according to a study published January 3 in Scientific Reports. The study consisted of 2,601 men from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study in eastern Finland. Cross-sectional associations with prevalence of self-reported frequent headache were estimated with adjusted odds ratios. Participants' average serum 25(OH)D concentration was 43.4 nmol/L. A total of 250 men reported frequent (ie, weekly or daily) headache. The average serum 25(OH)D concentration among those with frequent headache was 38.3 nmol/L and 43.9 nmol/L among those without frequent headache, after adjustment for age and year and month of blood draw. After multivariable adjustments, those in the lowest versus the highest serum 25(OH)D quartile had 113% higher odds for frequent headache.

Moderate postlunch napping is associated with better cognition in Chinese older adults, according to a cross-sectional study published online ahead of print December 20, 2016, in the Journal of the American Geriatrics Society. A total of 2,974 people age 65 and older from the China Health and Retirement Longitudinal Study were included in this study. Investigators conducted interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial abilities. Patients reported their postlunch napping habits. Postlunch napping was reported in 57.7% of participants (mean duration, 63 minutes). Cognitive function was significantly associated with napping. Moderate nappers had better overall cognition than nonnappers or extended nappers. Nonnappers also had significantly poorer cognition than short nappers.  

 
Physical exercise may be effective in the prevention of dementia, according to a study published in the January issue of the Journal of Alzheimer's Disease. Researchers assessed the interactive relationship of APOE genotype and physical exercise on dementia risk over a five-year period in 1,646 older adults from the Canadian Study of Health and Aging who were dementia-free at baseline. Physical exercise moderated the relationship between genotype and dementia. For APOE  ε4 noncarriers, the odds of developing dementia were higher in nonexercisers than in exercisers (odds ratio, 1.98). For APOE  ε4 carriers, the odds of developing dementia were not significantly different between nonexercisers and exercisers. "Given that most individuals are not at genetic risk, physical exercise may be an effective prevention strategy," the researchers concluded.

 
Lower adherence to a Mediterranean-type diet is predictive of total brain atrophy over a three-year period, according to a study published online ahead of print January 4 in Neurology. Researchers focused on total brain volume, gray matter volume, and cortical thickness. Investigators gathered information on the eating habits of 967 Scottish people at age 70. In regression models adjusting for relevant demographic and physical health indicators, lower adherence to the Mediterranean-type diet was associated with greater three-year reduction in total brain volume. Cross-sectional associations between Mediterranean-type diet and baseline MRI measures in 562 participants were not significant. Targeted analyses of meat and fish consumption did not replicate previous associations with total brain volume or total gray matter volume.

 
Children who sustain concussions have a 35% smaller neural response to pitch on average, according to a study published online ahead of print December 22, 2016, in Scientific Reports. Researchers studied 40 children with concussion and a control group. Children with concussion exhibited a signature neural profile. Children had worse representation of the fundamental frequency and smaller, more sluggish neural responses. As the children recovered from their head injuries, their ability to process pitch returned to normal. Neural processing of sound correctly identified 90% of concussion cases and cleared 95% of control cases, suggesting this approach has practical potential as a scalable biologic marker for sports-related concussion and other mild traumatic brain injuries.

People who are homeless sleep less and are more likely to have insomnia and daytime fatigue than people in the general population, according to a study published online ahead of print December 27, 2016, in JAMA Internal Medicine. Investigators analyzed survey responses from 3,453 people who were homeless (2,068 men; mean age, 39.8) and compared them with responses from individuals in the general population. Homeless people reported significantly shorter total sleep time than the general population (6 h 31 min vs 7 h 9 min). Eight percent reported less than four hours of total sleep time over the past 24 hours, compared with 3% of the general population. Homeless women were twice as likely as men to report that they slept less than four hours. Furthermore, insomnia was reported by 41% of homeless people, compared with 19% of controls.

—Kimberly Williams

Torsades de pointes (TdP) is a life-threatening ventricular arrhythmia that is associated with both congenital and acquired QT interval prolongation. QT interval prolongation is commonly observed in acute alcohol withdrawal and cirrhotic cardiomyopathy.^1-3 In both conditions, there is a positive correlation between the degree of QT interval prolongation and disease severity.^4,5 The precise mechanisms of QT interval prolongation in these conditions are not well understood. One hypothesis is that autonomic hyperexcitability results in altered ventricular repolarization and QT interval prolongation. This mechanism of QT prolongation has been found in acute alcohol withdrawal independent of electrolyte abnormalities, use of QT-prolonging medications, and cirrhosis.^1,2,6

The authors report the case of a veteran who was hospitalized for acute alcohol withdrawal and decompensated cirrhosis and was found to have a newly prolonged QT interval. On hospital day 3, the patient developed TdP, which required external defibrillation. Despite correction of electrolyte abnormalities, abstinence from alcohol, avoidance of QT-prolonging medications, and exclusion of cardiac ischemia, there was significant and persistent prolongation of the QT interval—ultimately attributed to cirrhotic cardiomyopathy. Acquired QT interval prolongation is common in both acute alcohol withdrawal and cirrhosis.This case highlights the importance of close monitoring of the QT interval and TdP susceptibility in patients being treated for acute alcohol withdrawal, particularly those with cirrhosis.

Case Report

A 66-year-old male veteran with a 35-year history of alcohol dependence presented for alcohol detoxification. He reported having drunk at least 32 ounces of vodka every day of the preceding 5 years and reported having unsuccessfully attempted self-detoxification several times. Prior detoxification efforts were unsuccessful because of intractable nausea and tremulousness. Additional presenting symptoms included lethargy, anorexia, and a fall with transient right-side hemiparesis (findings on magnetic resonance imaging of the head had been normal).

His medical history included type 2 diabetes, tobacco dependence, and macular degeneration. The only medication being taken was glargine 25 units daily. On admission, the patient was afebrile (98.1°F), normotensive (103/77 mm Hg), and oriented to person, place, and time. Examination also revealed a protuberant abdomen with caput medusae, and no shifting dullness or lower extremity edema. The neurologic examination was nonfocal.

Laboratory test results on admission were significant for elevated serum alcohol level (243.8 mg/dL); elevated levels of aspartate aminotransferase (144 units/L) alanine aminotransferase (25 units/L), and total bilirubin (4.2 mg/L); hypoalbuminemia; normocalemia; hypomagnesemia; normal corrected calcium level; and normal renal function (0.84 mg/dL)(Table). The patient’s admission Child-Pugh score of 10 indicated class C liver disease. Admission electrocardiogram (EKG) revealed normal sinus rhythm, first-degree atrioventricular block, and prolongation of the QTc interval (519 ms). Six years earlier, the patient’s QTc interval had been 409 ms (Figures 1 and 2). As QT interval depends on heart rate, it is most commonly expressed as corrected QT, or QTc, where QTc = QT/(√RR).

Symptom-triggered therapy for alcohol withdrawal was instituted, and the patient’s electrolyte abnormalities were corrected. Telemetry monitoring demonstrated polymorphic ventricular ectopy, including a 6.8-s run of polymorphic ventricular tachycardia and several shorter runs (4-10 beats) of nonsustained ventricular tachycardia, prompting initiation of a low-dose beta blocker. Based on elevated scores on the symptom-triggered scale for alcohol withdrawal, the Clinical Institute Withdrawal Assessement for Alcohol Withdrawal (CIWA), several doses of oral lorazepam were given for withdrawal symptoms.

The patient became increasingly confused, and new-onset nystagmus was noted. These findings raised concern for Wernicke encephalopathy, so the patient was empirically started on IV high-dose thiamine supplementation. The CIWA scores remained high, and there were frequent episodes of ventricular ectopy during the first 2 hospital days. Interval EKG revealed further prolongation of the QTc interval (549 ms) without evidence of cardiac ischemia (Figure 3). Cardiac enzymes were negative, and electrolyte levels were within normal limits.

Discussion

Alcohol dependence is a common chronic and relapsing disease that often requires controlled detoxification. Investigators have found a high incidence of QT interval prolongation in alcohol withdrawal and hepatic disease.^3,6 Common causes of QT interval prolongation in this setting are poor nutrition, electrolyte abnormalities (particularly hypocalcemia and hypomagnesemia), and use of certain medications.^1-3,7,8 In addition, alcohol is directly toxic to the renal tubules, resulting in renal wasting of divalent cations, which may persist up to 30 days after the most recent alcohol exposure.^9,10

The patient in this case report was initially thought to have hypomagnesemia-induced long QT syndrome (leading to TdP cardiac arrest), but the authors’ review of laboratory test results revealed the QT interval remained markedly prolonged, despite adequate correction of hypomagnesemia implicating the hyperadrenergic state of acute alcohol withdrawal in QT interval prolongation and TdP cardiac arrest. Interestingly, the QT interval remained prolonged 2 months after TdP arrest, despite sustained normalization of electrolyte levels and the absence of active ischemia or use of QT-prolonging medications.

Given the exclusion of other causes of QT interval prolongation, the authors hypothesized that autonomic hyperactivity of acute alcohol withdrawal and resultant QT interval prolongation were potentiated by underlying cirrhotic cardiomyopathy, a well described cause of QT interval prolongation. Cirrhotic cardiomyopathy is thought to cause QT interval prolongation by delayed repolarization of cardiomyocytes and promotion of sympatho-adrenergic hyperactivity.⁶ In other case series, TdP development has been associated with severe withdrawal symptoms, particularly delirium tremens.² In cirrhosis, QT interval prolongation often is described as an early manifestation of cirrhotic cardiomyopathy, irrespective of the underlying etiology, and precedes systolic and diastolic dysfunction.⁶

The magnitude of QT prolongation has been associated with severity of liver disease as expressed by Child-Pugh score, with reports of QT normalization after liver transplantation.^4,5 Patients with higher Child-Pugh scores should be considered to be at elevated risk for malignant ventricular arrhythmias. The authors recommend checking an EKG on admission of any patient who has liver disease or has presented for alcohol withdrawal. Patients with a prolonged QTc interval should be monitored on telemetry. The authors also recommend aggressive repletion of electrolytes, particularly potassium and magnesium, in patients who present with cirrhosis and alcohol withdrawal.

Avoidance of QT-prolonging medications is advisable for all patients with a long QT interval. Beta blockers shorten the QT interval in cirrhotic patients, but the role of beta blockers in preventing malignant arrhythmias in this group of patients is not yet clear.¹¹ The present patient’s QT interval had been normal before he developed cirrhotic liver disease. His presentation was suggestive of acquired long QT syndrome, likely caused by cirrhotic cardiomyopathy given the exhaustive exclusion of other causes of QT interval prolongation.

Conclusion

This case highlights the importance of close monitoring of the QT interval in patients being treated for acute alcohol withdrawal, particularly those with cirrhosis, and suggests that timely and aggressive management of withdrawal, repletion of electrolytes, and telemetry monitoring may prevent life-threatening arrhythmia.

Torsades de pointes (TdP) is a life-threatening ventricular arrhythmia that is associated with both congenital and acquired QT interval prolongation. QT interval prolongation is commonly observed in acute alcohol withdrawal and cirrhotic cardiomyopathy.^1-3 In both conditions, there is a positive correlation between the degree of QT interval prolongation and disease severity.^4,5 The precise mechanisms of QT interval prolongation in these conditions are not well understood. One hypothesis is that autonomic hyperexcitability results in altered ventricular repolarization and QT interval prolongation. This mechanism of QT prolongation has been found in acute alcohol withdrawal independent of electrolyte abnormalities, use of QT-prolonging medications, and cirrhosis.^1,2,6

The authors report the case of a veteran who was hospitalized for acute alcohol withdrawal and decompensated cirrhosis and was found to have a newly prolonged QT interval. On hospital day 3, the patient developed TdP, which required external defibrillation. Despite correction of electrolyte abnormalities, abstinence from alcohol, avoidance of QT-prolonging medications, and exclusion of cardiac ischemia, there was significant and persistent prolongation of the QT interval—ultimately attributed to cirrhotic cardiomyopathy. Acquired QT interval prolongation is common in both acute alcohol withdrawal and cirrhosis.This case highlights the importance of close monitoring of the QT interval and TdP susceptibility in patients being treated for acute alcohol withdrawal, particularly those with cirrhosis.

Case Report

A 66-year-old male veteran with a 35-year history of alcohol dependence presented for alcohol detoxification. He reported having drunk at least 32 ounces of vodka every day of the preceding 5 years and reported having unsuccessfully attempted self-detoxification several times. Prior detoxification efforts were unsuccessful because of intractable nausea and tremulousness. Additional presenting symptoms included lethargy, anorexia, and a fall with transient right-side hemiparesis (findings on magnetic resonance imaging of the head had been normal).

His medical history included type 2 diabetes, tobacco dependence, and macular degeneration. The only medication being taken was glargine 25 units daily. On admission, the patient was afebrile (98.1°F), normotensive (103/77 mm Hg), and oriented to person, place, and time. Examination also revealed a protuberant abdomen with caput medusae, and no shifting dullness or lower extremity edema. The neurologic examination was nonfocal.

Laboratory test results on admission were significant for elevated serum alcohol level (243.8 mg/dL); elevated levels of aspartate aminotransferase (144 units/L) alanine aminotransferase (25 units/L), and total bilirubin (4.2 mg/L); hypoalbuminemia; normocalemia; hypomagnesemia; normal corrected calcium level; and normal renal function (0.84 mg/dL)(Table). The patient’s admission Child-Pugh score of 10 indicated class C liver disease. Admission electrocardiogram (EKG) revealed normal sinus rhythm, first-degree atrioventricular block, and prolongation of the QTc interval (519 ms). Six years earlier, the patient’s QTc interval had been 409 ms (Figures 1 and 2). As QT interval depends on heart rate, it is most commonly expressed as corrected QT, or QTc, where QTc = QT/(√RR).

Symptom-triggered therapy for alcohol withdrawal was instituted, and the patient’s electrolyte abnormalities were corrected. Telemetry monitoring demonstrated polymorphic ventricular ectopy, including a 6.8-s run of polymorphic ventricular tachycardia and several shorter runs (4-10 beats) of nonsustained ventricular tachycardia, prompting initiation of a low-dose beta blocker. Based on elevated scores on the symptom-triggered scale for alcohol withdrawal, the Clinical Institute Withdrawal Assessement for Alcohol Withdrawal (CIWA), several doses of oral lorazepam were given for withdrawal symptoms.

The patient became increasingly confused, and new-onset nystagmus was noted. These findings raised concern for Wernicke encephalopathy, so the patient was empirically started on IV high-dose thiamine supplementation. The CIWA scores remained high, and there were frequent episodes of ventricular ectopy during the first 2 hospital days. Interval EKG revealed further prolongation of the QTc interval (549 ms) without evidence of cardiac ischemia (Figure 3). Cardiac enzymes were negative, and electrolyte levels were within normal limits.

Discussion

Alcohol dependence is a common chronic and relapsing disease that often requires controlled detoxification. Investigators have found a high incidence of QT interval prolongation in alcohol withdrawal and hepatic disease.^3,6 Common causes of QT interval prolongation in this setting are poor nutrition, electrolyte abnormalities (particularly hypocalcemia and hypomagnesemia), and use of certain medications.^1-3,7,8 In addition, alcohol is directly toxic to the renal tubules, resulting in renal wasting of divalent cations, which may persist up to 30 days after the most recent alcohol exposure.^9,10

The patient in this case report was initially thought to have hypomagnesemia-induced long QT syndrome (leading to TdP cardiac arrest), but the authors’ review of laboratory test results revealed the QT interval remained markedly prolonged, despite adequate correction of hypomagnesemia implicating the hyperadrenergic state of acute alcohol withdrawal in QT interval prolongation and TdP cardiac arrest. Interestingly, the QT interval remained prolonged 2 months after TdP arrest, despite sustained normalization of electrolyte levels and the absence of active ischemia or use of QT-prolonging medications.

Given the exclusion of other causes of QT interval prolongation, the authors hypothesized that autonomic hyperactivity of acute alcohol withdrawal and resultant QT interval prolongation were potentiated by underlying cirrhotic cardiomyopathy, a well described cause of QT interval prolongation. Cirrhotic cardiomyopathy is thought to cause QT interval prolongation by delayed repolarization of cardiomyocytes and promotion of sympatho-adrenergic hyperactivity.⁶ In other case series, TdP development has been associated with severe withdrawal symptoms, particularly delirium tremens.² In cirrhosis, QT interval prolongation often is described as an early manifestation of cirrhotic cardiomyopathy, irrespective of the underlying etiology, and precedes systolic and diastolic dysfunction.⁶

The magnitude of QT prolongation has been associated with severity of liver disease as expressed by Child-Pugh score, with reports of QT normalization after liver transplantation.^4,5 Patients with higher Child-Pugh scores should be considered to be at elevated risk for malignant ventricular arrhythmias. The authors recommend checking an EKG on admission of any patient who has liver disease or has presented for alcohol withdrawal. Patients with a prolonged QTc interval should be monitored on telemetry. The authors also recommend aggressive repletion of electrolytes, particularly potassium and magnesium, in patients who present with cirrhosis and alcohol withdrawal.

Avoidance of QT-prolonging medications is advisable for all patients with a long QT interval. Beta blockers shorten the QT interval in cirrhotic patients, but the role of beta blockers in preventing malignant arrhythmias in this group of patients is not yet clear.¹¹ The present patient’s QT interval had been normal before he developed cirrhotic liver disease. His presentation was suggestive of acquired long QT syndrome, likely caused by cirrhotic cardiomyopathy given the exhaustive exclusion of other causes of QT interval prolongation.

Conclusion

This case highlights the importance of close monitoring of the QT interval in patients being treated for acute alcohol withdrawal, particularly those with cirrhosis, and suggests that timely and aggressive management of withdrawal, repletion of electrolytes, and telemetry monitoring may prevent life-threatening arrhythmia.

Torsades de pointes (TdP) is a life-threatening ventricular arrhythmia that is associated with both congenital and acquired QT interval prolongation. QT interval prolongation is commonly observed in acute alcohol withdrawal and cirrhotic cardiomyopathy.^1-3 In both conditions, there is a positive correlation between the degree of QT interval prolongation and disease severity.^4,5 The precise mechanisms of QT interval prolongation in these conditions are not well understood. One hypothesis is that autonomic hyperexcitability results in altered ventricular repolarization and QT interval prolongation. This mechanism of QT prolongation has been found in acute alcohol withdrawal independent of electrolyte abnormalities, use of QT-prolonging medications, and cirrhosis.^1,2,6

The authors report the case of a veteran who was hospitalized for acute alcohol withdrawal and decompensated cirrhosis and was found to have a newly prolonged QT interval. On hospital day 3, the patient developed TdP, which required external defibrillation. Despite correction of electrolyte abnormalities, abstinence from alcohol, avoidance of QT-prolonging medications, and exclusion of cardiac ischemia, there was significant and persistent prolongation of the QT interval—ultimately attributed to cirrhotic cardiomyopathy. Acquired QT interval prolongation is common in both acute alcohol withdrawal and cirrhosis.This case highlights the importance of close monitoring of the QT interval and TdP susceptibility in patients being treated for acute alcohol withdrawal, particularly those with cirrhosis.

Case Report

A 66-year-old male veteran with a 35-year history of alcohol dependence presented for alcohol detoxification. He reported having drunk at least 32 ounces of vodka every day of the preceding 5 years and reported having unsuccessfully attempted self-detoxification several times. Prior detoxification efforts were unsuccessful because of intractable nausea and tremulousness. Additional presenting symptoms included lethargy, anorexia, and a fall with transient right-side hemiparesis (findings on magnetic resonance imaging of the head had been normal).

His medical history included type 2 diabetes, tobacco dependence, and macular degeneration. The only medication being taken was glargine 25 units daily. On admission, the patient was afebrile (98.1°F), normotensive (103/77 mm Hg), and oriented to person, place, and time. Examination also revealed a protuberant abdomen with caput medusae, and no shifting dullness or lower extremity edema. The neurologic examination was nonfocal.

Laboratory test results on admission were significant for elevated serum alcohol level (243.8 mg/dL); elevated levels of aspartate aminotransferase (144 units/L) alanine aminotransferase (25 units/L), and total bilirubin (4.2 mg/L); hypoalbuminemia; normocalemia; hypomagnesemia; normal corrected calcium level; and normal renal function (0.84 mg/dL)(Table). The patient’s admission Child-Pugh score of 10 indicated class C liver disease. Admission electrocardiogram (EKG) revealed normal sinus rhythm, first-degree atrioventricular block, and prolongation of the QTc interval (519 ms). Six years earlier, the patient’s QTc interval had been 409 ms (Figures 1 and 2). As QT interval depends on heart rate, it is most commonly expressed as corrected QT, or QTc, where QTc = QT/(√RR).

Symptom-triggered therapy for alcohol withdrawal was instituted, and the patient’s electrolyte abnormalities were corrected. Telemetry monitoring demonstrated polymorphic ventricular ectopy, including a 6.8-s run of polymorphic ventricular tachycardia and several shorter runs (4-10 beats) of nonsustained ventricular tachycardia, prompting initiation of a low-dose beta blocker. Based on elevated scores on the symptom-triggered scale for alcohol withdrawal, the Clinical Institute Withdrawal Assessement for Alcohol Withdrawal (CIWA), several doses of oral lorazepam were given for withdrawal symptoms.

The patient became increasingly confused, and new-onset nystagmus was noted. These findings raised concern for Wernicke encephalopathy, so the patient was empirically started on IV high-dose thiamine supplementation. The CIWA scores remained high, and there were frequent episodes of ventricular ectopy during the first 2 hospital days. Interval EKG revealed further prolongation of the QTc interval (549 ms) without evidence of cardiac ischemia (Figure 3). Cardiac enzymes were negative, and electrolyte levels were within normal limits.

Discussion

Alcohol dependence is a common chronic and relapsing disease that often requires controlled detoxification. Investigators have found a high incidence of QT interval prolongation in alcohol withdrawal and hepatic disease.^3,6 Common causes of QT interval prolongation in this setting are poor nutrition, electrolyte abnormalities (particularly hypocalcemia and hypomagnesemia), and use of certain medications.^1-3,7,8 In addition, alcohol is directly toxic to the renal tubules, resulting in renal wasting of divalent cations, which may persist up to 30 days after the most recent alcohol exposure.^9,10

The patient in this case report was initially thought to have hypomagnesemia-induced long QT syndrome (leading to TdP cardiac arrest), but the authors’ review of laboratory test results revealed the QT interval remained markedly prolonged, despite adequate correction of hypomagnesemia implicating the hyperadrenergic state of acute alcohol withdrawal in QT interval prolongation and TdP cardiac arrest. Interestingly, the QT interval remained prolonged 2 months after TdP arrest, despite sustained normalization of electrolyte levels and the absence of active ischemia or use of QT-prolonging medications.

Given the exclusion of other causes of QT interval prolongation, the authors hypothesized that autonomic hyperactivity of acute alcohol withdrawal and resultant QT interval prolongation were potentiated by underlying cirrhotic cardiomyopathy, a well described cause of QT interval prolongation. Cirrhotic cardiomyopathy is thought to cause QT interval prolongation by delayed repolarization of cardiomyocytes and promotion of sympatho-adrenergic hyperactivity.⁶ In other case series, TdP development has been associated with severe withdrawal symptoms, particularly delirium tremens.² In cirrhosis, QT interval prolongation often is described as an early manifestation of cirrhotic cardiomyopathy, irrespective of the underlying etiology, and precedes systolic and diastolic dysfunction.⁶

The magnitude of QT prolongation has been associated with severity of liver disease as expressed by Child-Pugh score, with reports of QT normalization after liver transplantation.^4,5 Patients with higher Child-Pugh scores should be considered to be at elevated risk for malignant ventricular arrhythmias. The authors recommend checking an EKG on admission of any patient who has liver disease or has presented for alcohol withdrawal. Patients with a prolonged QTc interval should be monitored on telemetry. The authors also recommend aggressive repletion of electrolytes, particularly potassium and magnesium, in patients who present with cirrhosis and alcohol withdrawal.

Avoidance of QT-prolonging medications is advisable for all patients with a long QT interval. Beta blockers shorten the QT interval in cirrhotic patients, but the role of beta blockers in preventing malignant arrhythmias in this group of patients is not yet clear.¹¹ The present patient’s QT interval had been normal before he developed cirrhotic liver disease. His presentation was suggestive of acquired long QT syndrome, likely caused by cirrhotic cardiomyopathy given the exhaustive exclusion of other causes of QT interval prolongation.

Conclusion

This case highlights the importance of close monitoring of the QT interval in patients being treated for acute alcohol withdrawal, particularly those with cirrhosis, and suggests that timely and aggressive management of withdrawal, repletion of electrolytes, and telemetry monitoring may prevent life-threatening arrhythmia.

A single cough can propel as many as 3,000 droplets into the air at a velocity of 6 to 28 m/s. The droplets travel in what classic fluid mechanics calls a “2-stage jet”: the starting jet (when the cough starts) and interrupted jet (when the cough stops). After the original cough ends, a “leading vortex” carries particles forward, but as the momentum slows, particles fall out of the jet according to researchers from the University of Hong Kong and Shenzhen Institute of Research and Innovation, both in China, who studied cough trajectories and the implications for disease transmission in buildings.

Once the penetration velocity drops below 0.01 m/s, environmental factors, such as ventilation and human body temperature, begin to influence the flow. Beyond 1 to 2 m, the exhaled air stream dissolves into the room airflow, and the pathogen-containing droplets or droplet nuclei are dispersed according to the global airflow in the room.

When a cough doesn’t last long, the researchers say, the velocity of fine particles decays significantly after the jet is interrupted. However, even short coughs have consequences: Pathogen-containing droplets as large as ≥ 5 µm in diameter can be directly deposited on the nasal or oral mucosa of a nearby “new host.”

But coughs differ in many ways, including how far and wide they send the droplets. The researchers conducted experiments to help determine spread by discharging dyed or particle-filled water into a water tank.  They examined 3 different temporal exit velocity profiles: pulsation, sinusoidal, and real-cough.

The “most striking phenomenon,” the researchers say, is that the particle clouds of all 3 sizes of particles (small [8-14 µm], medium [57-68 µm], large [96-114 µm]) penetrated almost the same distance at different time steps. In other words, large particles can travel as far as fine particles.

The cough flow’s maximum penetration distance was 53.4 to 69.7 opening diameter. That is, for a mouth opening to a diameter of 2 cm, the large particles could penetrate 1 to 1.4 m in a “real cough case,” they note. Cough duration was important in determining the spread range of particles. Their maximum travel distance was “much enhanced” in a long starting jet, especially for small particles.

Source:
Wei J, Li Y. PLoS One. 2017;12(1): e0169235.
doi:  10.1371/journal.pone.0169235.

A single cough can propel as many as 3,000 droplets into the air at a velocity of 6 to 28 m/s. The droplets travel in what classic fluid mechanics calls a “2-stage jet”: the starting jet (when the cough starts) and interrupted jet (when the cough stops). After the original cough ends, a “leading vortex” carries particles forward, but as the momentum slows, particles fall out of the jet according to researchers from the University of Hong Kong and Shenzhen Institute of Research and Innovation, both in China, who studied cough trajectories and the implications for disease transmission in buildings.

Once the penetration velocity drops below 0.01 m/s, environmental factors, such as ventilation and human body temperature, begin to influence the flow. Beyond 1 to 2 m, the exhaled air stream dissolves into the room airflow, and the pathogen-containing droplets or droplet nuclei are dispersed according to the global airflow in the room.

When a cough doesn’t last long, the researchers say, the velocity of fine particles decays significantly after the jet is interrupted. However, even short coughs have consequences: Pathogen-containing droplets as large as ≥ 5 µm in diameter can be directly deposited on the nasal or oral mucosa of a nearby “new host.”

But coughs differ in many ways, including how far and wide they send the droplets. The researchers conducted experiments to help determine spread by discharging dyed or particle-filled water into a water tank.  They examined 3 different temporal exit velocity profiles: pulsation, sinusoidal, and real-cough.

The “most striking phenomenon,” the researchers say, is that the particle clouds of all 3 sizes of particles (small [8-14 µm], medium [57-68 µm], large [96-114 µm]) penetrated almost the same distance at different time steps. In other words, large particles can travel as far as fine particles.

The cough flow’s maximum penetration distance was 53.4 to 69.7 opening diameter. That is, for a mouth opening to a diameter of 2 cm, the large particles could penetrate 1 to 1.4 m in a “real cough case,” they note. Cough duration was important in determining the spread range of particles. Their maximum travel distance was “much enhanced” in a long starting jet, especially for small particles.

Source:
Wei J, Li Y. PLoS One. 2017;12(1): e0169235.
doi:  10.1371/journal.pone.0169235.

A single cough can propel as many as 3,000 droplets into the air at a velocity of 6 to 28 m/s. The droplets travel in what classic fluid mechanics calls a “2-stage jet”: the starting jet (when the cough starts) and interrupted jet (when the cough stops). After the original cough ends, a “leading vortex” carries particles forward, but as the momentum slows, particles fall out of the jet according to researchers from the University of Hong Kong and Shenzhen Institute of Research and Innovation, both in China, who studied cough trajectories and the implications for disease transmission in buildings.

Once the penetration velocity drops below 0.01 m/s, environmental factors, such as ventilation and human body temperature, begin to influence the flow. Beyond 1 to 2 m, the exhaled air stream dissolves into the room airflow, and the pathogen-containing droplets or droplet nuclei are dispersed according to the global airflow in the room.

When a cough doesn’t last long, the researchers say, the velocity of fine particles decays significantly after the jet is interrupted. However, even short coughs have consequences: Pathogen-containing droplets as large as ≥ 5 µm in diameter can be directly deposited on the nasal or oral mucosa of a nearby “new host.”

But coughs differ in many ways, including how far and wide they send the droplets. The researchers conducted experiments to help determine spread by discharging dyed or particle-filled water into a water tank.  They examined 3 different temporal exit velocity profiles: pulsation, sinusoidal, and real-cough.

The “most striking phenomenon,” the researchers say, is that the particle clouds of all 3 sizes of particles (small [8-14 µm], medium [57-68 µm], large [96-114 µm]) penetrated almost the same distance at different time steps. In other words, large particles can travel as far as fine particles.

The cough flow’s maximum penetration distance was 53.4 to 69.7 opening diameter. That is, for a mouth opening to a diameter of 2 cm, the large particles could penetrate 1 to 1.4 m in a “real cough case,” they note. Cough duration was important in determining the spread range of particles. Their maximum travel distance was “much enhanced” in a long starting jet, especially for small particles.

Source:
Wei J, Li Y. PLoS One. 2017;12(1): e0169235.
doi:  10.1371/journal.pone.0169235.

Corrected mortality rates for cervical cancer indicate a greater disparity between races, according to a report in Cancer.

Because previous estimates did not adjust for women who’d had a hysterectomy or who were otherwise not at risk for cervical cancer, investigators performed a “corrected” analysis using data from the Behavioral Risk Factor Surveillance System and from the National Center for Health Statistics and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, for the years 2002 through 2012.

The corrected mortality rate in black women is 10.1 per 100,000 women (95% confidence interval, 9.6-10.6) and 4.7 per 100,000 in white women (95% CI, 4.6-4.8), an overall difference of 44%. The previous, uncorrected mortality rate for black women was 5.7 per 100,000 (95% CI, 5.5-6.0) and 3.2 per 100,000 (95% CI, 3.1-3.2) for white women, reported Anne F. Rositch, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her colleagues.

The corrected findings do not indicate a rise in the overall cervical cancer death rate, but do show that the disparity between the races is higher, despite declines in such deaths among black women over the years: The corrected analysis over the decade showed that the rate of decrease in cervical cancer mortality rates was 0.8% in white women and 3.6% in black women (P less than .05), Dr. Rositch and her associates reported (Cancer 2017 Jan 23 doi: 10.1002/cncr.30507). Both corrected and uncorrected rates were significantly higher in older black women, especially those 85 years and older at 18.6 per 100,000 (95% CI, 15.4-21.7) before correction, and 37.2 per 100,000 (95% CI, 31.0-43.5) after correction.

“Future research should focus on overcoming the underlying factors that contribute to this mortality gap (differential follow-up for abnormal Papanicolaou test results and barriers to care after diagnosis) and on determining why black women and older women receive different and inadequate treatment for the same disease,” wrote Dr. Rositch and her colleagues.

The elimination of mortality differences across the two races in women aged 20-29 years and those 35-39 years was “encouraging ... because these age cohorts correspond to the patients who are most likely to have been vaccinated against the human papillomavirus (HPV) virus,” Heather J. Dalton, MD, and John Farley, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix, Ariz., wrote in an accompanying editorial (Cancer 2017 Jan. 23 doi: 10.1002/cncr.30501).

High-risk HPV infections and lack of adequate screening are the “only factors definitely associated with the incidence of cervical cancer,” they noted.

[email protected]

On Twitter @whitneymcknight

Corrected mortality rates for cervical cancer indicate a greater disparity between races, according to a report in Cancer.

Because previous estimates did not adjust for women who’d had a hysterectomy or who were otherwise not at risk for cervical cancer, investigators performed a “corrected” analysis using data from the Behavioral Risk Factor Surveillance System and from the National Center for Health Statistics and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, for the years 2002 through 2012.

The corrected mortality rate in black women is 10.1 per 100,000 women (95% confidence interval, 9.6-10.6) and 4.7 per 100,000 in white women (95% CI, 4.6-4.8), an overall difference of 44%. The previous, uncorrected mortality rate for black women was 5.7 per 100,000 (95% CI, 5.5-6.0) and 3.2 per 100,000 (95% CI, 3.1-3.2) for white women, reported Anne F. Rositch, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her colleagues.

The corrected findings do not indicate a rise in the overall cervical cancer death rate, but do show that the disparity between the races is higher, despite declines in such deaths among black women over the years: The corrected analysis over the decade showed that the rate of decrease in cervical cancer mortality rates was 0.8% in white women and 3.6% in black women (P less than .05), Dr. Rositch and her associates reported (Cancer 2017 Jan 23 doi: 10.1002/cncr.30507). Both corrected and uncorrected rates were significantly higher in older black women, especially those 85 years and older at 18.6 per 100,000 (95% CI, 15.4-21.7) before correction, and 37.2 per 100,000 (95% CI, 31.0-43.5) after correction.

“Future research should focus on overcoming the underlying factors that contribute to this mortality gap (differential follow-up for abnormal Papanicolaou test results and barriers to care after diagnosis) and on determining why black women and older women receive different and inadequate treatment for the same disease,” wrote Dr. Rositch and her colleagues.

The elimination of mortality differences across the two races in women aged 20-29 years and those 35-39 years was “encouraging ... because these age cohorts correspond to the patients who are most likely to have been vaccinated against the human papillomavirus (HPV) virus,” Heather J. Dalton, MD, and John Farley, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix, Ariz., wrote in an accompanying editorial (Cancer 2017 Jan. 23 doi: 10.1002/cncr.30501).

High-risk HPV infections and lack of adequate screening are the “only factors definitely associated with the incidence of cervical cancer,” they noted.

[email protected]

On Twitter @whitneymcknight

Corrected mortality rates for cervical cancer indicate a greater disparity between races, according to a report in Cancer.

Because previous estimates did not adjust for women who’d had a hysterectomy or who were otherwise not at risk for cervical cancer, investigators performed a “corrected” analysis using data from the Behavioral Risk Factor Surveillance System and from the National Center for Health Statistics and the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, for the years 2002 through 2012.

The corrected mortality rate in black women is 10.1 per 100,000 women (95% confidence interval, 9.6-10.6) and 4.7 per 100,000 in white women (95% CI, 4.6-4.8), an overall difference of 44%. The previous, uncorrected mortality rate for black women was 5.7 per 100,000 (95% CI, 5.5-6.0) and 3.2 per 100,000 (95% CI, 3.1-3.2) for white women, reported Anne F. Rositch, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and her colleagues.

The corrected findings do not indicate a rise in the overall cervical cancer death rate, but do show that the disparity between the races is higher, despite declines in such deaths among black women over the years: The corrected analysis over the decade showed that the rate of decrease in cervical cancer mortality rates was 0.8% in white women and 3.6% in black women (P less than .05), Dr. Rositch and her associates reported (Cancer 2017 Jan 23 doi: 10.1002/cncr.30507). Both corrected and uncorrected rates were significantly higher in older black women, especially those 85 years and older at 18.6 per 100,000 (95% CI, 15.4-21.7) before correction, and 37.2 per 100,000 (95% CI, 31.0-43.5) after correction.

“Future research should focus on overcoming the underlying factors that contribute to this mortality gap (differential follow-up for abnormal Papanicolaou test results and barriers to care after diagnosis) and on determining why black women and older women receive different and inadequate treatment for the same disease,” wrote Dr. Rositch and her colleagues.

The elimination of mortality differences across the two races in women aged 20-29 years and those 35-39 years was “encouraging ... because these age cohorts correspond to the patients who are most likely to have been vaccinated against the human papillomavirus (HPV) virus,” Heather J. Dalton, MD, and John Farley, MD, of Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center, Phoenix, Ariz., wrote in an accompanying editorial (Cancer 2017 Jan. 23 doi: 10.1002/cncr.30501).

High-risk HPV infections and lack of adequate screening are the “only factors definitely associated with the incidence of cervical cancer,” they noted.

[email protected]

On Twitter @whitneymcknight

HOUSTON—Pharmaceutical-grade cannabidiol (CBD) may reduce seizure severity in adults and children with medically refractory epilepsy, according to an open-label trial described at the 70th Annual Meeting of the American Epilepsy Society. A controlled trial to confirm the drug’s effect may be warranted.

Jennifer L. DeWolfe, DO, Associate Professor of Neurology at the University of Alabama at Birmingham, and colleagues conducted a state-sponsored compassionate-use study of CBD in patients with refractory epilepsy. Patients received Epidiolex (a CBD formulation developed by GW Pharmaceuticals) in addition to their antiepileptic drugs. Eligible participants were adults and children with epilepsy confirmed by video EEG. Participants were required to have failed four antiepileptic drugs and had to have had four countable seizures per month. Exclusion criteria included psychogenic nonepileptic seizures confirmed by video EEG and prior CBD use.

Measuring Seizure Severity Over Time

The investigators measured participants’ seizure frequency and used the Chalfont Seizure Severity Scale to measure seizure severity. The scale solicits information about various factors, such as whether the patient lost awareness, dropped an object, fell, or was injured. The total possible score on the scale is 178, and the score increases with seizure severity. Changes of 10 or more points were considered significant. The researchers particularly focused on participants’ most frequent seizure type, which the Chalfont Seizure Severity Scale names the Type 1 seizure.

Dr. DeWolfe and colleagues measured patients’ total seizure severity scores and severity scores for Type 1 seizures at baseline, three months, and six months. To compare the scores, the researchers calculated time-weighted average values. They also examined percent change in seizures; seizure severity in adults, children, and all patients; and severity in responders and nonresponders. Responders were defined as patients who had a reduction in seizure frequency of more than 50%. The analysis included 81 participants, approximately half of whom were children. At the time of the analysis, 57 patients had undergone evaluation at three months, and 47 patients had undergone evaluation at six months. At baseline, the majority of patients had at least two types of seizures.

Seizure Severity Was Reduced

The total change in Chalfont Seizure Severity Scale score at three months was significant for adults, children, and all patients. The change remained significant at six months. The difference in the percent change in seizure severity between responders and nonresponders was significant at three months, but not at six months.

The change in severity of Type 1 seizures was significant for adults, children, and all patients at three months and at six months. The difference between responders and nonresponders in change in severity of Type 1 seizures was significant at three months, but not at six months.

At three months, the majority of adults, the majority of all patients, the majority of responders, and the majority of nonresponders had a reduction in seizure severity of at least 10 points. Approximately one-third of children had a reduction in seizure severity of at least 10 points at three months. At six months, the majority of adults, children, all patients, responders, and nonresponders had a decrease in seizure severity of at least 10 points. Patients’ average seizure severity tended to increase at six months, compared with the three-month point, but was still significantly lower than at baseline.

“One of the things I find most exciting is [that] … even if you were considered a nonresponder, you still had improvement in seizure severity,” said Dr. DeWolfe. She and her colleagues plan to examine the data by seizure type (eg, absence or tonic-clonic), to identify which factors measured by the Chalfont Seizure Severity Scale contributed most to the reductions in seizure severity, and to examine whether the effect of CBD on levels of antiepileptic drugs contributed to the change in seizure severity. The findings of this open-label trial suggest that CBD may improve seizure severity in people with medically refractory epilepsy. Randomized placebo-controlled studies are needed to further evaluate the effects of CBD on seizure severity.

—Erik Greb

Suggested Reading

Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.

Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013;29(3):574-577.

HOUSTON—Pharmaceutical-grade cannabidiol (CBD) may reduce seizure severity in adults and children with medically refractory epilepsy, according to an open-label trial described at the 70th Annual Meeting of the American Epilepsy Society. A controlled trial to confirm the drug’s effect may be warranted.

Jennifer L. DeWolfe, DO, Associate Professor of Neurology at the University of Alabama at Birmingham, and colleagues conducted a state-sponsored compassionate-use study of CBD in patients with refractory epilepsy. Patients received Epidiolex (a CBD formulation developed by GW Pharmaceuticals) in addition to their antiepileptic drugs. Eligible participants were adults and children with epilepsy confirmed by video EEG. Participants were required to have failed four antiepileptic drugs and had to have had four countable seizures per month. Exclusion criteria included psychogenic nonepileptic seizures confirmed by video EEG and prior CBD use.

Measuring Seizure Severity Over Time

The investigators measured participants’ seizure frequency and used the Chalfont Seizure Severity Scale to measure seizure severity. The scale solicits information about various factors, such as whether the patient lost awareness, dropped an object, fell, or was injured. The total possible score on the scale is 178, and the score increases with seizure severity. Changes of 10 or more points were considered significant. The researchers particularly focused on participants’ most frequent seizure type, which the Chalfont Seizure Severity Scale names the Type 1 seizure.

Dr. DeWolfe and colleagues measured patients’ total seizure severity scores and severity scores for Type 1 seizures at baseline, three months, and six months. To compare the scores, the researchers calculated time-weighted average values. They also examined percent change in seizures; seizure severity in adults, children, and all patients; and severity in responders and nonresponders. Responders were defined as patients who had a reduction in seizure frequency of more than 50%. The analysis included 81 participants, approximately half of whom were children. At the time of the analysis, 57 patients had undergone evaluation at three months, and 47 patients had undergone evaluation at six months. At baseline, the majority of patients had at least two types of seizures.

Seizure Severity Was Reduced

The total change in Chalfont Seizure Severity Scale score at three months was significant for adults, children, and all patients. The change remained significant at six months. The difference in the percent change in seizure severity between responders and nonresponders was significant at three months, but not at six months.

The change in severity of Type 1 seizures was significant for adults, children, and all patients at three months and at six months. The difference between responders and nonresponders in change in severity of Type 1 seizures was significant at three months, but not at six months.

At three months, the majority of adults, the majority of all patients, the majority of responders, and the majority of nonresponders had a reduction in seizure severity of at least 10 points. Approximately one-third of children had a reduction in seizure severity of at least 10 points at three months. At six months, the majority of adults, children, all patients, responders, and nonresponders had a decrease in seizure severity of at least 10 points. Patients’ average seizure severity tended to increase at six months, compared with the three-month point, but was still significantly lower than at baseline.

“One of the things I find most exciting is [that] … even if you were considered a nonresponder, you still had improvement in seizure severity,” said Dr. DeWolfe. She and her colleagues plan to examine the data by seizure type (eg, absence or tonic-clonic), to identify which factors measured by the Chalfont Seizure Severity Scale contributed most to the reductions in seizure severity, and to examine whether the effect of CBD on levels of antiepileptic drugs contributed to the change in seizure severity. The findings of this open-label trial suggest that CBD may improve seizure severity in people with medically refractory epilepsy. Randomized placebo-controlled studies are needed to further evaluate the effects of CBD on seizure severity.

—Erik Greb

Suggested Reading

Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.

Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013;29(3):574-577.

HOUSTON—Pharmaceutical-grade cannabidiol (CBD) may reduce seizure severity in adults and children with medically refractory epilepsy, according to an open-label trial described at the 70th Annual Meeting of the American Epilepsy Society. A controlled trial to confirm the drug’s effect may be warranted.

Jennifer L. DeWolfe, DO, Associate Professor of Neurology at the University of Alabama at Birmingham, and colleagues conducted a state-sponsored compassionate-use study of CBD in patients with refractory epilepsy. Patients received Epidiolex (a CBD formulation developed by GW Pharmaceuticals) in addition to their antiepileptic drugs. Eligible participants were adults and children with epilepsy confirmed by video EEG. Participants were required to have failed four antiepileptic drugs and had to have had four countable seizures per month. Exclusion criteria included psychogenic nonepileptic seizures confirmed by video EEG and prior CBD use.

Measuring Seizure Severity Over Time

The investigators measured participants’ seizure frequency and used the Chalfont Seizure Severity Scale to measure seizure severity. The scale solicits information about various factors, such as whether the patient lost awareness, dropped an object, fell, or was injured. The total possible score on the scale is 178, and the score increases with seizure severity. Changes of 10 or more points were considered significant. The researchers particularly focused on participants’ most frequent seizure type, which the Chalfont Seizure Severity Scale names the Type 1 seizure.

Dr. DeWolfe and colleagues measured patients’ total seizure severity scores and severity scores for Type 1 seizures at baseline, three months, and six months. To compare the scores, the researchers calculated time-weighted average values. They also examined percent change in seizures; seizure severity in adults, children, and all patients; and severity in responders and nonresponders. Responders were defined as patients who had a reduction in seizure frequency of more than 50%. The analysis included 81 participants, approximately half of whom were children. At the time of the analysis, 57 patients had undergone evaluation at three months, and 47 patients had undergone evaluation at six months. At baseline, the majority of patients had at least two types of seizures.

Seizure Severity Was Reduced

The total change in Chalfont Seizure Severity Scale score at three months was significant for adults, children, and all patients. The change remained significant at six months. The difference in the percent change in seizure severity between responders and nonresponders was significant at three months, but not at six months.

The change in severity of Type 1 seizures was significant for adults, children, and all patients at three months and at six months. The difference between responders and nonresponders in change in severity of Type 1 seizures was significant at three months, but not at six months.

At three months, the majority of adults, the majority of all patients, the majority of responders, and the majority of nonresponders had a reduction in seizure severity of at least 10 points. Approximately one-third of children had a reduction in seizure severity of at least 10 points at three months. At six months, the majority of adults, children, all patients, responders, and nonresponders had a decrease in seizure severity of at least 10 points. Patients’ average seizure severity tended to increase at six months, compared with the three-month point, but was still significantly lower than at baseline.

“One of the things I find most exciting is [that] … even if you were considered a nonresponder, you still had improvement in seizure severity,” said Dr. DeWolfe. She and her colleagues plan to examine the data by seizure type (eg, absence or tonic-clonic), to identify which factors measured by the Chalfont Seizure Severity Scale contributed most to the reductions in seizure severity, and to examine whether the effect of CBD on levels of antiepileptic drugs contributed to the change in seizure severity. The findings of this open-label trial suggest that CBD may improve seizure severity in people with medically refractory epilepsy. Randomized placebo-controlled studies are needed to further evaluate the effects of CBD on seizure severity.

—Erik Greb

Suggested Reading

Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.

Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav. 2013;29(3):574-577.

As you may have read, accountable care organizations have met uneven success over the last several years. But, when they are broken down into categories, physician-sponsored ACOs have done better, particularly those with a strong primary care core.

This is true for several reasons.

In this transition period from a fee-for-service payment system that rewards volume and expensive inpatient care to a pay-for-value system, some ACOs set up by health systems or specialists envisioned the savings coming through lower utilization of their services. They had an inherent impediment to fully committing to keeping people well and avoiding acute care. In contrast, primary care providers are free to be all in with population health value-based programs.

New upfront payments are game changers

A successful ACO will be assigned one or more patient populations and be given a minimum of 50% of the savings for the overall costs for those populations, if the quality of their health is maintained or improved.

To excise avoidable waste, the ACO looks at gaps in care for those populations – frequent emergency department use for nonemergencies, avoidably high levels of diabetes and obesity, too-high readmission rates, unnecessarily high postacute care costs, etc. They then use evidence-based best team care practices – from patient self care and prevention, to multispecialty coordination and PCMH care management.

Why? Because these proved to give the highest impact on quality and reducing costs. To achieve significant shared savings, the costs are usually measured for a calendar year, then it takes about 6 months for the claims to be reported and paid. Thus, the shared savings check to the ACO will arrive about 18 months after all this is started.

The CMS has also figured out that primary care physician care coordination and management drive quality and savings. The agency knows that incentivizing this type of care, the very type calculated to create ACO success, will net significant savings to the Medicare program.

For example, the pilot project for preventing diabetes will be expanded, because Medicare hopes to save several thousand dollars a year per beneficiary in health care costs.

In a blog entry the day the expanded population health management codes were announced, the CMS acting administrator wrote that, “Over time, if the clinicians qualified to provide these services were to fully provide these services to all eligible beneficiaries, the increase would be as much as $4 billion or more in additional support for care coordination and patient-centered care.”

CMS revenue streams to support ACO success-driving activities include:

• Value-based screening and counseling codes to decrease downstream costs.

• Upward adjustment of evaluation and management reimbursement for assessment of care and care plan development for mobility-impaired patients.

• Annual wellness visits.

• Prolonged E&M services that accrue outside of a patient visit.

• Collaboration with mental health specialists.

• Comprehensive assessment and care planning for patients with cognitive impairment.

• Expansion of the diabetes prevention pilot program; diabetes prevention and diabetes education are two separate services.

• Transitional care management for high-risk patients post discharge.

• Structured obesity management.

The 2017 Medicare fee schedule smoothed some of the bumps in administering and being paid for chronic care management (CCM) services, and it added codes with increased reimbursement aligned with increased complexity of comorbidities/illness.

Perhaps the biggest new payment boost for primary care to engage in ACO high-value activities is actually the Merit-Based Incentive Payment System (MIPS) under MACRA, the Medicare Access and CHIP Reauthorization Act of 2015.

Under MACRA, all Medicare compensation for physicians will be determined by relative delivery of quality and efficient care. Experts are recommending that primary care physicians participate in non–risk-taking ACOs to optimize MIPS value scoring, while also reducing administrative burdens of compliance. Use an ACO’s analytics to support collaborative care and provide the reports required under MIPS.

Let’s be smart about it

According to Gordon Wilhoit, MD, a practicing physician and chief medical officer of an all–primary-care-physician ACO in South Carolina, “This is a no brainer. Start first with your MSSP ACO high-value game plan, then align the complementary care coordination codes, CCM, MIPS, and other revenue stream and reporting activities with it. Now, primary care physicians can finance their ACO and MIPS care coordination efforts with a stream of ongoing payments from these care management codes.

“One of my colleagues saw a 27% increase in revenues in 6 months just from providing and billing for this type of care,” Dr. Wilhoit explained. “And, not counting shared savings or MIPS incentive payments, our office’s reimbursement from these care management codes now exceeds our fee-for-service income, which has not decreased.”

Even with these payments, the CMS will reduce overall net expenditures. Your impact on health care will be more powerful as a manager of the team addressing patients’ overall health than reacting to patient sickness one at a time. The patients you impact the most may be ones you don’t actually see. Your empowerment to practice medicine the right way will continue to grow.

Now, finally, you may start getting compensation that takes away the last big hurdle to creating the infrastructure you need to succeed.
 

Mr. Bobbitt is a head of the health law group at the Smith Anderson law firm in Raleigh, N.C. He is president of, and Dr. Wilhoit is a consultant with, Value Health Partners, LLC, a health care strategic consulting company. He has years of experience assisting physicians form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at either [email protected] or 919-906-4054.

As you may have read, accountable care organizations have met uneven success over the last several years. But, when they are broken down into categories, physician-sponsored ACOs have done better, particularly those with a strong primary care core.

This is true for several reasons.

In this transition period from a fee-for-service payment system that rewards volume and expensive inpatient care to a pay-for-value system, some ACOs set up by health systems or specialists envisioned the savings coming through lower utilization of their services. They had an inherent impediment to fully committing to keeping people well and avoiding acute care. In contrast, primary care providers are free to be all in with population health value-based programs.

New upfront payments are game changers

A successful ACO will be assigned one or more patient populations and be given a minimum of 50% of the savings for the overall costs for those populations, if the quality of their health is maintained or improved.

To excise avoidable waste, the ACO looks at gaps in care for those populations – frequent emergency department use for nonemergencies, avoidably high levels of diabetes and obesity, too-high readmission rates, unnecessarily high postacute care costs, etc. They then use evidence-based best team care practices – from patient self care and prevention, to multispecialty coordination and PCMH care management.

Why? Because these proved to give the highest impact on quality and reducing costs. To achieve significant shared savings, the costs are usually measured for a calendar year, then it takes about 6 months for the claims to be reported and paid. Thus, the shared savings check to the ACO will arrive about 18 months after all this is started.

The CMS has also figured out that primary care physician care coordination and management drive quality and savings. The agency knows that incentivizing this type of care, the very type calculated to create ACO success, will net significant savings to the Medicare program.

For example, the pilot project for preventing diabetes will be expanded, because Medicare hopes to save several thousand dollars a year per beneficiary in health care costs.

In a blog entry the day the expanded population health management codes were announced, the CMS acting administrator wrote that, “Over time, if the clinicians qualified to provide these services were to fully provide these services to all eligible beneficiaries, the increase would be as much as $4 billion or more in additional support for care coordination and patient-centered care.”

CMS revenue streams to support ACO success-driving activities include:

• Value-based screening and counseling codes to decrease downstream costs.

• Upward adjustment of evaluation and management reimbursement for assessment of care and care plan development for mobility-impaired patients.

• Annual wellness visits.

• Prolonged E&M services that accrue outside of a patient visit.

• Collaboration with mental health specialists.

• Comprehensive assessment and care planning for patients with cognitive impairment.

• Expansion of the diabetes prevention pilot program; diabetes prevention and diabetes education are two separate services.

• Transitional care management for high-risk patients post discharge.

• Structured obesity management.

The 2017 Medicare fee schedule smoothed some of the bumps in administering and being paid for chronic care management (CCM) services, and it added codes with increased reimbursement aligned with increased complexity of comorbidities/illness.

Perhaps the biggest new payment boost for primary care to engage in ACO high-value activities is actually the Merit-Based Incentive Payment System (MIPS) under MACRA, the Medicare Access and CHIP Reauthorization Act of 2015.

Under MACRA, all Medicare compensation for physicians will be determined by relative delivery of quality and efficient care. Experts are recommending that primary care physicians participate in non–risk-taking ACOs to optimize MIPS value scoring, while also reducing administrative burdens of compliance. Use an ACO’s analytics to support collaborative care and provide the reports required under MIPS.

Let’s be smart about it

According to Gordon Wilhoit, MD, a practicing physician and chief medical officer of an all–primary-care-physician ACO in South Carolina, “This is a no brainer. Start first with your MSSP ACO high-value game plan, then align the complementary care coordination codes, CCM, MIPS, and other revenue stream and reporting activities with it. Now, primary care physicians can finance their ACO and MIPS care coordination efforts with a stream of ongoing payments from these care management codes.

“One of my colleagues saw a 27% increase in revenues in 6 months just from providing and billing for this type of care,” Dr. Wilhoit explained. “And, not counting shared savings or MIPS incentive payments, our office’s reimbursement from these care management codes now exceeds our fee-for-service income, which has not decreased.”

Even with these payments, the CMS will reduce overall net expenditures. Your impact on health care will be more powerful as a manager of the team addressing patients’ overall health than reacting to patient sickness one at a time. The patients you impact the most may be ones you don’t actually see. Your empowerment to practice medicine the right way will continue to grow.

Now, finally, you may start getting compensation that takes away the last big hurdle to creating the infrastructure you need to succeed.
 

Mr. Bobbitt is a head of the health law group at the Smith Anderson law firm in Raleigh, N.C. He is president of, and Dr. Wilhoit is a consultant with, Value Health Partners, LLC, a health care strategic consulting company. He has years of experience assisting physicians form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at either [email protected] or 919-906-4054.

As you may have read, accountable care organizations have met uneven success over the last several years. But, when they are broken down into categories, physician-sponsored ACOs have done better, particularly those with a strong primary care core.

This is true for several reasons.

In this transition period from a fee-for-service payment system that rewards volume and expensive inpatient care to a pay-for-value system, some ACOs set up by health systems or specialists envisioned the savings coming through lower utilization of their services. They had an inherent impediment to fully committing to keeping people well and avoiding acute care. In contrast, primary care providers are free to be all in with population health value-based programs.

New upfront payments are game changers

A successful ACO will be assigned one or more patient populations and be given a minimum of 50% of the savings for the overall costs for those populations, if the quality of their health is maintained or improved.

To excise avoidable waste, the ACO looks at gaps in care for those populations – frequent emergency department use for nonemergencies, avoidably high levels of diabetes and obesity, too-high readmission rates, unnecessarily high postacute care costs, etc. They then use evidence-based best team care practices – from patient self care and prevention, to multispecialty coordination and PCMH care management.

Why? Because these proved to give the highest impact on quality and reducing costs. To achieve significant shared savings, the costs are usually measured for a calendar year, then it takes about 6 months for the claims to be reported and paid. Thus, the shared savings check to the ACO will arrive about 18 months after all this is started.

The CMS has also figured out that primary care physician care coordination and management drive quality and savings. The agency knows that incentivizing this type of care, the very type calculated to create ACO success, will net significant savings to the Medicare program.

For example, the pilot project for preventing diabetes will be expanded, because Medicare hopes to save several thousand dollars a year per beneficiary in health care costs.

In a blog entry the day the expanded population health management codes were announced, the CMS acting administrator wrote that, “Over time, if the clinicians qualified to provide these services were to fully provide these services to all eligible beneficiaries, the increase would be as much as $4 billion or more in additional support for care coordination and patient-centered care.”

CMS revenue streams to support ACO success-driving activities include:

• Value-based screening and counseling codes to decrease downstream costs.

• Upward adjustment of evaluation and management reimbursement for assessment of care and care plan development for mobility-impaired patients.

• Annual wellness visits.

• Prolonged E&M services that accrue outside of a patient visit.

• Collaboration with mental health specialists.

• Comprehensive assessment and care planning for patients with cognitive impairment.

• Expansion of the diabetes prevention pilot program; diabetes prevention and diabetes education are two separate services.

• Transitional care management for high-risk patients post discharge.

• Structured obesity management.

The 2017 Medicare fee schedule smoothed some of the bumps in administering and being paid for chronic care management (CCM) services, and it added codes with increased reimbursement aligned with increased complexity of comorbidities/illness.

Perhaps the biggest new payment boost for primary care to engage in ACO high-value activities is actually the Merit-Based Incentive Payment System (MIPS) under MACRA, the Medicare Access and CHIP Reauthorization Act of 2015.

Under MACRA, all Medicare compensation for physicians will be determined by relative delivery of quality and efficient care. Experts are recommending that primary care physicians participate in non–risk-taking ACOs to optimize MIPS value scoring, while also reducing administrative burdens of compliance. Use an ACO’s analytics to support collaborative care and provide the reports required under MIPS.

Let’s be smart about it

According to Gordon Wilhoit, MD, a practicing physician and chief medical officer of an all–primary-care-physician ACO in South Carolina, “This is a no brainer. Start first with your MSSP ACO high-value game plan, then align the complementary care coordination codes, CCM, MIPS, and other revenue stream and reporting activities with it. Now, primary care physicians can finance their ACO and MIPS care coordination efforts with a stream of ongoing payments from these care management codes.

“One of my colleagues saw a 27% increase in revenues in 6 months just from providing and billing for this type of care,” Dr. Wilhoit explained. “And, not counting shared savings or MIPS incentive payments, our office’s reimbursement from these care management codes now exceeds our fee-for-service income, which has not decreased.”

Even with these payments, the CMS will reduce overall net expenditures. Your impact on health care will be more powerful as a manager of the team addressing patients’ overall health than reacting to patient sickness one at a time. The patients you impact the most may be ones you don’t actually see. Your empowerment to practice medicine the right way will continue to grow.

Now, finally, you may start getting compensation that takes away the last big hurdle to creating the infrastructure you need to succeed.
 

Mr. Bobbitt is a head of the health law group at the Smith Anderson law firm in Raleigh, N.C. He is president of, and Dr. Wilhoit is a consultant with, Value Health Partners, LLC, a health care strategic consulting company. He has years of experience assisting physicians form integrated delivery systems. He has spoken and written nationally to primary care physicians on the strategies and practicalities of forming or joining ACOs. This article is meant to be educational and does not constitute legal advice. For additional information, readers may contact the author at either [email protected] or 919-906-4054.

HOUSTON—Nearly one in three children diagnosed with new-onset epilepsy presents with psychiatric diagnoses at the onset, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

This finding “tells us that when kids are coming in, even if they are only having psychiatric symptoms at their onset of epilepsy, they should be referred for some treatment to help them possibly mitigate the development of these psychiatric diagnoses in the first year,” said Julia Doss, PsyD, Pediatric Psychologist at the Minnesota Epilepsy Group in Saint Paul.

About three years ago, the Minnesota Epilepsy Group, a private practice group that consults with the United Hospital and Children’s Hospitals and Clinics of Minnesota, launched a New Onset Pediatric Epilepsy (NOPE) clinic. At this clinic, referred patients undergo a psychologic evaluation, neuropsychologic testing, and medical evaluation in the same day. Psychologic assessment measures include the Clinical Interview with parent and patient, the Strengths and Difficulties Questionnaire (SDQ), and the Revised Children’s Anxiety and Depression Scale (RCADS).

Researchers evaluated 96 patients in the clinic who had presented for their first NOPE clinic visit within eight weeks of their epilepsy diagnosis. More than half were male, and patients ranged in age from 3 to 18. Dr. Doss and her colleagues separated the children into the following three groups: ages 3 to 6 (group 1), ages 7 to 11 (group 2), and ages 12 to 18 (group 3). Based on the Clinical Interview, none of the patients in group 1 screened positive for depression or anxiety, but 16% met criteria for some other behavioral disorder. However, among patients in group 2, the percentages who met criteria for depression, anxiety, and other behavioral disorders were 13%, 25%, and 13%, respectively. The corresponding percentages for patients in group 3 were 29%, 38%, and 10%.

Of the 96 patients evaluated, 64 parents completed all of the questions on the SDQ. The researchers observed significant correlations between parent response and diagnoses assigned on the Clinical Interview for behavior diagnoses and anxiety diagnoses) but not for depression diagnoses.

“Despite the correlations on both behavior and anxiety responses and clinical diagnoses assigned, parents still only reported significant concerns in about half of the children that were given diagnoses,” said Dr. Doss.

The comparison of RCADS scores between parent and child demonstrated moderate to strong correlation on the following scales: separation anxiety, generalized anxiety, obsessive/compulsive, and depression.

Small sample size was a key limitation in this study, said Dr. Doss. “Early evaluation or at least screening is necessary in all of our kids who present with an epilepsy diagnosis, because more than 30% develop psychiatric disorders within the first year of their diagnosis,” said Dr. Doss. “That’s one in three, so if we can start to better evaluate that early and get them funneled into treatment early, we might be able to prevent some of these problems from becoming lifelong issues.”

—Doug Brunk

Suggested Reading

Asato MR, Doss JL, Piloplys S. Clinic-friendly screening for cognitive and mental health problems in school-aged youth with epilepsy. Epilepsy Behav. 2015;48:97-102.

Piloplys S, Doss J, Siddarth P, et al. Risk factors for comorbid psychopathology in youth with psychogenic nonepileptic seizures. Seizure. 2016;38:32-37.

HOUSTON—Nearly one in three children diagnosed with new-onset epilepsy presents with psychiatric diagnoses at the onset, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

This finding “tells us that when kids are coming in, even if they are only having psychiatric symptoms at their onset of epilepsy, they should be referred for some treatment to help them possibly mitigate the development of these psychiatric diagnoses in the first year,” said Julia Doss, PsyD, Pediatric Psychologist at the Minnesota Epilepsy Group in Saint Paul.

About three years ago, the Minnesota Epilepsy Group, a private practice group that consults with the United Hospital and Children’s Hospitals and Clinics of Minnesota, launched a New Onset Pediatric Epilepsy (NOPE) clinic. At this clinic, referred patients undergo a psychologic evaluation, neuropsychologic testing, and medical evaluation in the same day. Psychologic assessment measures include the Clinical Interview with parent and patient, the Strengths and Difficulties Questionnaire (SDQ), and the Revised Children’s Anxiety and Depression Scale (RCADS).

Researchers evaluated 96 patients in the clinic who had presented for their first NOPE clinic visit within eight weeks of their epilepsy diagnosis. More than half were male, and patients ranged in age from 3 to 18. Dr. Doss and her colleagues separated the children into the following three groups: ages 3 to 6 (group 1), ages 7 to 11 (group 2), and ages 12 to 18 (group 3). Based on the Clinical Interview, none of the patients in group 1 screened positive for depression or anxiety, but 16% met criteria for some other behavioral disorder. However, among patients in group 2, the percentages who met criteria for depression, anxiety, and other behavioral disorders were 13%, 25%, and 13%, respectively. The corresponding percentages for patients in group 3 were 29%, 38%, and 10%.

Of the 96 patients evaluated, 64 parents completed all of the questions on the SDQ. The researchers observed significant correlations between parent response and diagnoses assigned on the Clinical Interview for behavior diagnoses and anxiety diagnoses) but not for depression diagnoses.

“Despite the correlations on both behavior and anxiety responses and clinical diagnoses assigned, parents still only reported significant concerns in about half of the children that were given diagnoses,” said Dr. Doss.

The comparison of RCADS scores between parent and child demonstrated moderate to strong correlation on the following scales: separation anxiety, generalized anxiety, obsessive/compulsive, and depression.

Small sample size was a key limitation in this study, said Dr. Doss. “Early evaluation or at least screening is necessary in all of our kids who present with an epilepsy diagnosis, because more than 30% develop psychiatric disorders within the first year of their diagnosis,” said Dr. Doss. “That’s one in three, so if we can start to better evaluate that early and get them funneled into treatment early, we might be able to prevent some of these problems from becoming lifelong issues.”

—Doug Brunk

Suggested Reading

Asato MR, Doss JL, Piloplys S. Clinic-friendly screening for cognitive and mental health problems in school-aged youth with epilepsy. Epilepsy Behav. 2015;48:97-102.

Piloplys S, Doss J, Siddarth P, et al. Risk factors for comorbid psychopathology in youth with psychogenic nonepileptic seizures. Seizure. 2016;38:32-37.

HOUSTON—Nearly one in three children diagnosed with new-onset epilepsy presents with psychiatric diagnoses at the onset, according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

This finding “tells us that when kids are coming in, even if they are only having psychiatric symptoms at their onset of epilepsy, they should be referred for some treatment to help them possibly mitigate the development of these psychiatric diagnoses in the first year,” said Julia Doss, PsyD, Pediatric Psychologist at the Minnesota Epilepsy Group in Saint Paul.

About three years ago, the Minnesota Epilepsy Group, a private practice group that consults with the United Hospital and Children’s Hospitals and Clinics of Minnesota, launched a New Onset Pediatric Epilepsy (NOPE) clinic. At this clinic, referred patients undergo a psychologic evaluation, neuropsychologic testing, and medical evaluation in the same day. Psychologic assessment measures include the Clinical Interview with parent and patient, the Strengths and Difficulties Questionnaire (SDQ), and the Revised Children’s Anxiety and Depression Scale (RCADS).

Researchers evaluated 96 patients in the clinic who had presented for their first NOPE clinic visit within eight weeks of their epilepsy diagnosis. More than half were male, and patients ranged in age from 3 to 18. Dr. Doss and her colleagues separated the children into the following three groups: ages 3 to 6 (group 1), ages 7 to 11 (group 2), and ages 12 to 18 (group 3). Based on the Clinical Interview, none of the patients in group 1 screened positive for depression or anxiety, but 16% met criteria for some other behavioral disorder. However, among patients in group 2, the percentages who met criteria for depression, anxiety, and other behavioral disorders were 13%, 25%, and 13%, respectively. The corresponding percentages for patients in group 3 were 29%, 38%, and 10%.

Of the 96 patients evaluated, 64 parents completed all of the questions on the SDQ. The researchers observed significant correlations between parent response and diagnoses assigned on the Clinical Interview for behavior diagnoses and anxiety diagnoses) but not for depression diagnoses.

“Despite the correlations on both behavior and anxiety responses and clinical diagnoses assigned, parents still only reported significant concerns in about half of the children that were given diagnoses,” said Dr. Doss.

The comparison of RCADS scores between parent and child demonstrated moderate to strong correlation on the following scales: separation anxiety, generalized anxiety, obsessive/compulsive, and depression.

Small sample size was a key limitation in this study, said Dr. Doss. “Early evaluation or at least screening is necessary in all of our kids who present with an epilepsy diagnosis, because more than 30% develop psychiatric disorders within the first year of their diagnosis,” said Dr. Doss. “That’s one in three, so if we can start to better evaluate that early and get them funneled into treatment early, we might be able to prevent some of these problems from becoming lifelong issues.”

—Doug Brunk

Suggested Reading

Asato MR, Doss JL, Piloplys S. Clinic-friendly screening for cognitive and mental health problems in school-aged youth with epilepsy. Epilepsy Behav. 2015;48:97-102.

Piloplys S, Doss J, Siddarth P, et al. Risk factors for comorbid psychopathology in youth with psychogenic nonepileptic seizures. Seizure. 2016;38:32-37.

NEW ORLEANS—Elderly patients with heart failure have a significantly increased prevalence of dementia and mild cognitive impairment (MCI), compared with people of similar age without heart failure, according to an analysis of data collected from more than 6,000 US residents enrolled in a long-term observational study.

Patients diagnosed with either heart failure with reduced ejection fraction or heart failure with preserved ejection fraction had an 89% increased prevalence of dementia and a 41% increased prevalence of MCI, compared with people from the same cohort who did not develop heart failure. Investigators adjusted their analysis for several demographic and clinical variables, said Lucy S. Witt, MD, a researcher at the University of North Carolina in Chapel Hill, at the American Heart Association Scientific Sessions 2016. She speculated that the link between heart failure and dementia and MCI might result from impaired cerebral perfusion in patients with heart failure or from effects from heart failure medications.

“Our findings suggest that clinicians should have a higher suspicion for cognitive impairment in patients with heart failure, regardless of other, more classic risk factors,” she said. “This knowledge could prompt physicians to perform testing [for dementia and MCI], initiate conversations regarding the goals of care or advance care planning, and discuss appropriate living situations” for their patients with heart failure.

The analysis used data collected for the Atherosclerosis Risk in Communities (ARIC) study, which began in 1987 and enrolled a randomly selected representative cohort of approximately 16,000 women and men between ages 45 and 64 who resided in any of four US communities. Dr. Witt specifically focused on the data collected from 6,431 of the participants who returned for a fifth follow-up examination between 2011 and 2013, including 5,490 people without heart failure, whose average age was 76, and 941 participants with heart failure, whose average age was 78.

The adjusted rate of dementia prevalence at the fifth follow-up visit was 5.6% among those without heart failure and 7.0% in those with heart failure. The examinations also found MCI in an adjusted 21.5% of those without heart failure and in 26.2% of those with heart failure, said Dr. Witt. Adjustments were for factors such as age, sex, location, education, hypertension, diabetes, depression, alcohol and tobacco use, cerebrovascular disease, and marital status.

The relative risk for dementia among patients with heart failure was roughly similar, regardless of whether ARIC participants had a reduced or preserved left ventricular ejection fraction, she said.

ARIC is funded by the National Heart, Lung, and Blood Institute. Dr. Witt had no disclosures.

—Mitchel L. Zoler

Suggested Reading

Adelborg K, Horváth-Puhó E, Ording A, et al. Heart failure and risk of dementia: a Danish nationwide population-based cohort study. Eur J Heart Fail. 2016 Sep 9 [Epub ahead of print].

Ampadu J, Morley JE. Heart failure and cognitive dysfunction. Int J Cardiol. 2015;178:12-23.

Rusanen M, Kivipelto M, Levälahti E, et al. Heart diseases and long-term risk of dementia and Alzheimer’s disease: a population-based CAIDE study. J Alzheimers Dis. 2014;42(1):183-191.

NEW ORLEANS—Elderly patients with heart failure have a significantly increased prevalence of dementia and mild cognitive impairment (MCI), compared with people of similar age without heart failure, according to an analysis of data collected from more than 6,000 US residents enrolled in a long-term observational study.

Patients diagnosed with either heart failure with reduced ejection fraction or heart failure with preserved ejection fraction had an 89% increased prevalence of dementia and a 41% increased prevalence of MCI, compared with people from the same cohort who did not develop heart failure. Investigators adjusted their analysis for several demographic and clinical variables, said Lucy S. Witt, MD, a researcher at the University of North Carolina in Chapel Hill, at the American Heart Association Scientific Sessions 2016. She speculated that the link between heart failure and dementia and MCI might result from impaired cerebral perfusion in patients with heart failure or from effects from heart failure medications.

“Our findings suggest that clinicians should have a higher suspicion for cognitive impairment in patients with heart failure, regardless of other, more classic risk factors,” she said. “This knowledge could prompt physicians to perform testing [for dementia and MCI], initiate conversations regarding the goals of care or advance care planning, and discuss appropriate living situations” for their patients with heart failure.

The analysis used data collected for the Atherosclerosis Risk in Communities (ARIC) study, which began in 1987 and enrolled a randomly selected representative cohort of approximately 16,000 women and men between ages 45 and 64 who resided in any of four US communities. Dr. Witt specifically focused on the data collected from 6,431 of the participants who returned for a fifth follow-up examination between 2011 and 2013, including 5,490 people without heart failure, whose average age was 76, and 941 participants with heart failure, whose average age was 78.

The adjusted rate of dementia prevalence at the fifth follow-up visit was 5.6% among those without heart failure and 7.0% in those with heart failure. The examinations also found MCI in an adjusted 21.5% of those without heart failure and in 26.2% of those with heart failure, said Dr. Witt. Adjustments were for factors such as age, sex, location, education, hypertension, diabetes, depression, alcohol and tobacco use, cerebrovascular disease, and marital status.

The relative risk for dementia among patients with heart failure was roughly similar, regardless of whether ARIC participants had a reduced or preserved left ventricular ejection fraction, she said.

ARIC is funded by the National Heart, Lung, and Blood Institute. Dr. Witt had no disclosures.

—Mitchel L. Zoler

Suggested Reading

Adelborg K, Horváth-Puhó E, Ording A, et al. Heart failure and risk of dementia: a Danish nationwide population-based cohort study. Eur J Heart Fail. 2016 Sep 9 [Epub ahead of print].

Ampadu J, Morley JE. Heart failure and cognitive dysfunction. Int J Cardiol. 2015;178:12-23.

Rusanen M, Kivipelto M, Levälahti E, et al. Heart diseases and long-term risk of dementia and Alzheimer’s disease: a population-based CAIDE study. J Alzheimers Dis. 2014;42(1):183-191.

NEW ORLEANS—Elderly patients with heart failure have a significantly increased prevalence of dementia and mild cognitive impairment (MCI), compared with people of similar age without heart failure, according to an analysis of data collected from more than 6,000 US residents enrolled in a long-term observational study.

Patients diagnosed with either heart failure with reduced ejection fraction or heart failure with preserved ejection fraction had an 89% increased prevalence of dementia and a 41% increased prevalence of MCI, compared with people from the same cohort who did not develop heart failure. Investigators adjusted their analysis for several demographic and clinical variables, said Lucy S. Witt, MD, a researcher at the University of North Carolina in Chapel Hill, at the American Heart Association Scientific Sessions 2016. She speculated that the link between heart failure and dementia and MCI might result from impaired cerebral perfusion in patients with heart failure or from effects from heart failure medications.

“Our findings suggest that clinicians should have a higher suspicion for cognitive impairment in patients with heart failure, regardless of other, more classic risk factors,” she said. “This knowledge could prompt physicians to perform testing [for dementia and MCI], initiate conversations regarding the goals of care or advance care planning, and discuss appropriate living situations” for their patients with heart failure.

The analysis used data collected for the Atherosclerosis Risk in Communities (ARIC) study, which began in 1987 and enrolled a randomly selected representative cohort of approximately 16,000 women and men between ages 45 and 64 who resided in any of four US communities. Dr. Witt specifically focused on the data collected from 6,431 of the participants who returned for a fifth follow-up examination between 2011 and 2013, including 5,490 people without heart failure, whose average age was 76, and 941 participants with heart failure, whose average age was 78.

The adjusted rate of dementia prevalence at the fifth follow-up visit was 5.6% among those without heart failure and 7.0% in those with heart failure. The examinations also found MCI in an adjusted 21.5% of those without heart failure and in 26.2% of those with heart failure, said Dr. Witt. Adjustments were for factors such as age, sex, location, education, hypertension, diabetes, depression, alcohol and tobacco use, cerebrovascular disease, and marital status.

The relative risk for dementia among patients with heart failure was roughly similar, regardless of whether ARIC participants had a reduced or preserved left ventricular ejection fraction, she said.

ARIC is funded by the National Heart, Lung, and Blood Institute. Dr. Witt had no disclosures.

—Mitchel L. Zoler

Suggested Reading

Adelborg K, Horváth-Puhó E, Ording A, et al. Heart failure and risk of dementia: a Danish nationwide population-based cohort study. Eur J Heart Fail. 2016 Sep 9 [Epub ahead of print].

Ampadu J, Morley JE. Heart failure and cognitive dysfunction. Int J Cardiol. 2015;178:12-23.

Rusanen M, Kivipelto M, Levälahti E, et al. Heart diseases and long-term risk of dementia and Alzheimer’s disease: a population-based CAIDE study. J Alzheimers Dis. 2014;42(1):183-191.

HOUSTON—Predictors of poor outcomes in patients with status epilepticus admitted to the neurointensive care unit include complex partial status epilepticus (CPSE), refractory status epilepticus, or the development of nonconvulsive status epilepticus (NCSE), according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

“Not a lot of data exist as to what predicts the poor outcomes and what’s known about the outcome in patients with status epilepticus,” said Advait Mahulikar, MD, a neurology resident at Wayne State University in Detroit.

Dr. Mahulikar and colleagues retrospectively reviewed data from 100 patients with status epilepticus who were admitted to the neurointensive care unit at Detroit Medical Center from November 2013 to January 2016. Variables of interest included patient demographics, initial presentation, refractoriness to treatment, presence or absence of underlying etiology, past history of epilepsy, and use of benzodiazepines on admission. NCSE was another variable of interest, either from initial presentation or developed during the course of convulsive status epilepticus. A good outcome was defined as a Glasgow Outcome Scale (GOS) score of 4 or 5, and a poor outcome was defined as a GOS score of 1 to 3.

The mean age of the 100 patients was 58; 53% were male, 84% were African American, and 70% had a history of epilepsy. The median hospital length of stay was seven days and the median neurointensive care unit length of stay was three days. Good outcomes occurred in 69 patients.

Neither age nor gender predicted poor outcome, and there was no difference in outcome between structural and nonstructural causes of status epilepticus. However, prior history of epilepsy was a strong negative predictor of poor outcome. Fourteen out of 70 patients (20%) with a prior history of epilepsy had a poor outcome. “The theory is that [these patients] were already on treatment for epilepsy in the past and that affected their outcome in a positive way,” said Dr. Mahulikar.

When outcome was analyzed based on status semiology on initial presentation, poor outcome was observed in 16 of the 37 patients (43%) with CPSE, nine of 48 patients (19%) with generalized convulsive status epilepticus, all patients with myoclonic status epilepticus (n = 2), and three of nine (33%) who had NCSE. The type of status epilepticus was unknown for four patients, one of whom had an unknown outcome. NCSE at any time during the hospital course was seen in 31 patients; 14 (45%) had a poor outcome.

The mean number of ventilator days was higher in patients with NCSE than in those without NCSE (9.2 vs 1.6 days) and also higher in those with new-onset seizures than in those without (7.8 vs. 2.9 days). Analysis of methods of treatment revealed that only seven of 31 (22.5%) patients who received adequate benzodiazepine dosing had poor outcomes.

“The take-home message is to diagnose NCSE as early as possible,” said Dr. Mahulikar. Neurologists may attribute some cases incorrectly to metabolic or autoimmune causes on their initial presentation. “Treat aggressively at the beginning,” Dr. Mahulikar advised.

—Doug Brunk

Suggested Reading

Power KN, Gramstad A, Gilhus NE, Englesen BA. Prognostic factors of status epilepticus in adults. Epileptic Disord. 2016;18(3):297-304.

Sutter R, De Marchis GM, Semmlack S, et al. Anesthetics and outcome in status epilepticus: A matched two-center cohort study. CNS Drugs. 2017;31(1):655-674.

HOUSTON—Predictors of poor outcomes in patients with status epilepticus admitted to the neurointensive care unit include complex partial status epilepticus (CPSE), refractory status epilepticus, or the development of nonconvulsive status epilepticus (NCSE), according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

“Not a lot of data exist as to what predicts the poor outcomes and what’s known about the outcome in patients with status epilepticus,” said Advait Mahulikar, MD, a neurology resident at Wayne State University in Detroit.

Dr. Mahulikar and colleagues retrospectively reviewed data from 100 patients with status epilepticus who were admitted to the neurointensive care unit at Detroit Medical Center from November 2013 to January 2016. Variables of interest included patient demographics, initial presentation, refractoriness to treatment, presence or absence of underlying etiology, past history of epilepsy, and use of benzodiazepines on admission. NCSE was another variable of interest, either from initial presentation or developed during the course of convulsive status epilepticus. A good outcome was defined as a Glasgow Outcome Scale (GOS) score of 4 or 5, and a poor outcome was defined as a GOS score of 1 to 3.

The mean age of the 100 patients was 58; 53% were male, 84% were African American, and 70% had a history of epilepsy. The median hospital length of stay was seven days and the median neurointensive care unit length of stay was three days. Good outcomes occurred in 69 patients.

Neither age nor gender predicted poor outcome, and there was no difference in outcome between structural and nonstructural causes of status epilepticus. However, prior history of epilepsy was a strong negative predictor of poor outcome. Fourteen out of 70 patients (20%) with a prior history of epilepsy had a poor outcome. “The theory is that [these patients] were already on treatment for epilepsy in the past and that affected their outcome in a positive way,” said Dr. Mahulikar.

When outcome was analyzed based on status semiology on initial presentation, poor outcome was observed in 16 of the 37 patients (43%) with CPSE, nine of 48 patients (19%) with generalized convulsive status epilepticus, all patients with myoclonic status epilepticus (n = 2), and three of nine (33%) who had NCSE. The type of status epilepticus was unknown for four patients, one of whom had an unknown outcome. NCSE at any time during the hospital course was seen in 31 patients; 14 (45%) had a poor outcome.

The mean number of ventilator days was higher in patients with NCSE than in those without NCSE (9.2 vs 1.6 days) and also higher in those with new-onset seizures than in those without (7.8 vs. 2.9 days). Analysis of methods of treatment revealed that only seven of 31 (22.5%) patients who received adequate benzodiazepine dosing had poor outcomes.

“The take-home message is to diagnose NCSE as early as possible,” said Dr. Mahulikar. Neurologists may attribute some cases incorrectly to metabolic or autoimmune causes on their initial presentation. “Treat aggressively at the beginning,” Dr. Mahulikar advised.

—Doug Brunk

Suggested Reading

Power KN, Gramstad A, Gilhus NE, Englesen BA. Prognostic factors of status epilepticus in adults. Epileptic Disord. 2016;18(3):297-304.

Sutter R, De Marchis GM, Semmlack S, et al. Anesthetics and outcome in status epilepticus: A matched two-center cohort study. CNS Drugs. 2017;31(1):655-674.

HOUSTON—Predictors of poor outcomes in patients with status epilepticus admitted to the neurointensive care unit include complex partial status epilepticus (CPSE), refractory status epilepticus, or the development of nonconvulsive status epilepticus (NCSE), according to research presented at the 70th Annual Meeting of the American Epilepsy Society.

“Not a lot of data exist as to what predicts the poor outcomes and what’s known about the outcome in patients with status epilepticus,” said Advait Mahulikar, MD, a neurology resident at Wayne State University in Detroit.

Dr. Mahulikar and colleagues retrospectively reviewed data from 100 patients with status epilepticus who were admitted to the neurointensive care unit at Detroit Medical Center from November 2013 to January 2016. Variables of interest included patient demographics, initial presentation, refractoriness to treatment, presence or absence of underlying etiology, past history of epilepsy, and use of benzodiazepines on admission. NCSE was another variable of interest, either from initial presentation or developed during the course of convulsive status epilepticus. A good outcome was defined as a Glasgow Outcome Scale (GOS) score of 4 or 5, and a poor outcome was defined as a GOS score of 1 to 3.

The mean age of the 100 patients was 58; 53% were male, 84% were African American, and 70% had a history of epilepsy. The median hospital length of stay was seven days and the median neurointensive care unit length of stay was three days. Good outcomes occurred in 69 patients.

Neither age nor gender predicted poor outcome, and there was no difference in outcome between structural and nonstructural causes of status epilepticus. However, prior history of epilepsy was a strong negative predictor of poor outcome. Fourteen out of 70 patients (20%) with a prior history of epilepsy had a poor outcome. “The theory is that [these patients] were already on treatment for epilepsy in the past and that affected their outcome in a positive way,” said Dr. Mahulikar.

When outcome was analyzed based on status semiology on initial presentation, poor outcome was observed in 16 of the 37 patients (43%) with CPSE, nine of 48 patients (19%) with generalized convulsive status epilepticus, all patients with myoclonic status epilepticus (n = 2), and three of nine (33%) who had NCSE. The type of status epilepticus was unknown for four patients, one of whom had an unknown outcome. NCSE at any time during the hospital course was seen in 31 patients; 14 (45%) had a poor outcome.

The mean number of ventilator days was higher in patients with NCSE than in those without NCSE (9.2 vs 1.6 days) and also higher in those with new-onset seizures than in those without (7.8 vs. 2.9 days). Analysis of methods of treatment revealed that only seven of 31 (22.5%) patients who received adequate benzodiazepine dosing had poor outcomes.

“The take-home message is to diagnose NCSE as early as possible,” said Dr. Mahulikar. Neurologists may attribute some cases incorrectly to metabolic or autoimmune causes on their initial presentation. “Treat aggressively at the beginning,” Dr. Mahulikar advised.

—Doug Brunk

Suggested Reading

Power KN, Gramstad A, Gilhus NE, Englesen BA. Prognostic factors of status epilepticus in adults. Epileptic Disord. 2016;18(3):297-304.

Sutter R, De Marchis GM, Semmlack S, et al. Anesthetics and outcome in status epilepticus: A matched two-center cohort study. CNS Drugs. 2017;31(1):655-674.