Journal of Clinical Outcomes Management

SAN DIEGO – To prevent dementia, follow Mom’s advice: Get up off the couch, go play with your friends, and eat your vegetables.

Michele G. Sullivan/MDedge News

After 15 years of disappointing drug trials, strong new evidence says the best way to attack Alzheimer’s disease is not to treat it once it develops, but to prevent it in the first place, Laura D. Baker, PhD, said at the Clinical Trials on Alzheimer’s Disease conference. Studies of exercise, cognitive and social stimulation, and diet show that each one can reduce the risk of dementia, and that a combination of all three may have even a more powerful and synergistic effect.

“We have become absolutely phobic of exercise,” said Dr. Baker of Wake Forest University, Winston-Salem, N.C. And it’s not just structured exercise we shirk. “We take the closest parking space, sit for hours on end, don’t even take the stairs. Yet we know from years of work that exercise has a powerful benefit on cardiovascular disease, lipid profiles, metabolic disease, stress, and mood. Now we are seeing that exercise also promotes brain health in normal aging and protects against cognitive decline and prevention.”
 

Get off the couch

The general benefits of exercise – chiefly aerobic exercise – are myriad, Dr. Baker said.

“Exercise increases effective neurorepair. It reduces oxidative stress. It improves insulin sensitivity and helps with maintaining normal weight. It reduces inflammation and increases normal clearance of amyloid-beta.”

A 2017 meta-analysis reviewed some of these findings. “The current review [of 16 studies] suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex, and the medial temporal areas. ... Moreover, aerobic exercise may increase functional connectivity or activation in the hippocampus, cingulate cortex, and parahippocampal gyrus regions,” wrote Mo-yi Li, PhD, of Fujian University of Traditional Chinese Medicine, Fuzhou, China, and colleagues.

Exercise increases brain-derived neurotrophic factor (BDNF), which in turn increases neuronal potentiation and synaptic plasticity. BDNF is also important in hippocampal neurogenesis; mice, after just one aerobic session, showed dramatic boosts in BDNF. A 2018 review elaborates on these findings.

Eat right

Diet mediates dementia risk through less direct, but very effective, pathways, Dr. Baker said. Diets rich in vegetables, berries, nuts, fish, lean proteins, and healthy fats improves virtually all metabolic measures. These, in turn, reduce the risk cerebrovascular disease – an important driver of vascular dementias and a contributor to Alzheimer’s disease risk as well.

The MIND diet study (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), reported in 2015 was a very successful demonstration of this concept. A combination of the Mediterranean diet and the DASH diet (Dietary Approaches to Stop Hypertension), the MIND diet stresses frequent consumption of vegetables – especially leafy greens – as well as nuts, berries, whole grains, fish, poultry, and wine or grape juice. In the large, nearly 5-year study of 923 subjects aged 58-98 years, the MIND diet was associated with significant gains in cognition – equivalent to a 7-year reversal of age. After 4.5 years, those who strictly adhered to the diet had a 53% reduction in risk for Alzheimer’s disease, and those who adhered moderately had a 35% reduction. And in a more recent Australian longitudinal study, the MIND diet was associated with a 53% reduced risk of cognitive impairment over 12 years.

Ketogenic diets also may exert a benefit. Theoretically, a state of ketosis forces the brain to burn ketones as an alternative fuel to glucose, thus boosting brain function in glucose-starved brains. A small pilot study with exploratory cognitive endpoints determined that diet-compliant subjects with mild to moderate Alzheimer’s experienced a mean 5-point improvement in the Alzheimer’s Disease Assessment Score–Cognition. They reverted to baseline scores within a month of ending the study.

Recent initial work into the gut microbiome provides some additional speculative, but interesting, data. A dysregulated microbiome can shift microbial populations toward a more inflammatory profile. Some work suggests that inflammatory cytokines then travel to the brain and induce a hyperresponse of neuron-damaging immune cells. A comprehensive review article discusses the complicated mechanisms that may be in play.

Play with your friends

Cognitive stimulation and social interaction also appear to modify dementia risk, although the data are a little more limited. But personal interaction is a key element of Dr. Baker’s ongoing EXERT trial.

The ongoing phase 3 trial randomized 300 adults with amnestic mild cognitive impairment to moderate to high intensity aerobic exercise plus one-on-one support at local YMCA gyms or a low-intensity stretching, balance, and range of motion program. In additional to cognitive testing, the trial includes brain imaging, cerebrospinal fluid sampling for biomarkers of Alzheimer’s disease, and a sleep study.

A key component is personal interaction with a trainer. “They spend a lot of one-on-one time with each person,” Dr. Baker said. “For me, that’s the crucial ingredient – that personal touch. It’s what helps people move from Point A to Point B in their behaviors.”

Virtual cognitive stimulation is also a burgeoning area of dementia prevention research right now. Numerous studies are ongoing to test whether virtual reality or other computer-based games might keep the mind sharp or even improve cognition in people at risk.
 

The power of three

If one lifestyle change can reduce dementia risk, what happens when all three work together?

That’s the newest question, first successfully explored in the mid-2000s, with the FINGER study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability). In FINGER, the triad of exercise, personal support at the gym, and a modified Mediterranean diet reduced Alzheimer’s disease risk and improved cognition relative to the control group.

FINGER showed that the intervention was feasible and that it was associated with cognitive preservation and reduced Alzheimer’s disease risk in a group of at-risk subjects. The active group also had a 25% greater improvement on a neuropsychological test battery relative to the control group. They also performed 150% better in processing speed, 83% better in executive function, and 40% better in short-term memory. They showed no increased risk of cognitive decline relative to the control group, which experienced a 30% increase in risk, according to lead investigator Miia Kivipelto, PhD, of the Karolinska Institute, Stockholm.

So successful was FINGER that it launched a global consortium of related studies called World Wide FINGERS. Active in six countries now, including the United States, the studies aim to discover whether such combinations of lifestyle interventions are workable across countries and cultures. World Wide FINGERS is largely supported by the Alzheimer’s Association.

Global enthusiasm for lifestyle interventions

In recognition of the importance of lifestyle changes for dementia prevention, the World Health Organization recently published “Risk reduction of cognitive decline and dementia.” The document reviews many studies and makes recommendations regarding not only exercise, diet, and cognitive stimulation, but also smoking and alcohol.

Research interest in these areas is surging, Dr. Baker said. “The [U.S.] National Institute on Aging now has 29 ongoing trials. There’s a strong commitment to investigations into how lifestyle interventions could protect brain health as we get older. Certainly, many fit and healthy people do develop Alzheimer’s. But for some, it could be medicine.”

But no matter how compliant people are, lifestyle changes will never completely rid the world of Alzheimer’s and other dementias. The view of Dr. Baker – and most other Alzheimer’s researchers – is to employ lifestyle changes to reduce risk as much as possible and not to stop when cognitive problems do present.

“We need to understand how lifestyle interventions might work in combination with pharmaceuticals,” she said. “If we can support the health of the body and the health of the mind, lifestyle interventions can be the fertilizer that would help drug therapy have its maximum effect.”

[email protected]

SAN DIEGO – To prevent dementia, follow Mom’s advice: Get up off the couch, go play with your friends, and eat your vegetables.

Michele G. Sullivan/MDedge News

After 15 years of disappointing drug trials, strong new evidence says the best way to attack Alzheimer’s disease is not to treat it once it develops, but to prevent it in the first place, Laura D. Baker, PhD, said at the Clinical Trials on Alzheimer’s Disease conference. Studies of exercise, cognitive and social stimulation, and diet show that each one can reduce the risk of dementia, and that a combination of all three may have even a more powerful and synergistic effect.

“We have become absolutely phobic of exercise,” said Dr. Baker of Wake Forest University, Winston-Salem, N.C. And it’s not just structured exercise we shirk. “We take the closest parking space, sit for hours on end, don’t even take the stairs. Yet we know from years of work that exercise has a powerful benefit on cardiovascular disease, lipid profiles, metabolic disease, stress, and mood. Now we are seeing that exercise also promotes brain health in normal aging and protects against cognitive decline and prevention.”
 

Get off the couch

The general benefits of exercise – chiefly aerobic exercise – are myriad, Dr. Baker said.

“Exercise increases effective neurorepair. It reduces oxidative stress. It improves insulin sensitivity and helps with maintaining normal weight. It reduces inflammation and increases normal clearance of amyloid-beta.”

A 2017 meta-analysis reviewed some of these findings. “The current review [of 16 studies] suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex, and the medial temporal areas. ... Moreover, aerobic exercise may increase functional connectivity or activation in the hippocampus, cingulate cortex, and parahippocampal gyrus regions,” wrote Mo-yi Li, PhD, of Fujian University of Traditional Chinese Medicine, Fuzhou, China, and colleagues.

Exercise increases brain-derived neurotrophic factor (BDNF), which in turn increases neuronal potentiation and synaptic plasticity. BDNF is also important in hippocampal neurogenesis; mice, after just one aerobic session, showed dramatic boosts in BDNF. A 2018 review elaborates on these findings.

Eat right

Diet mediates dementia risk through less direct, but very effective, pathways, Dr. Baker said. Diets rich in vegetables, berries, nuts, fish, lean proteins, and healthy fats improves virtually all metabolic measures. These, in turn, reduce the risk cerebrovascular disease – an important driver of vascular dementias and a contributor to Alzheimer’s disease risk as well.

The MIND diet study (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), reported in 2015 was a very successful demonstration of this concept. A combination of the Mediterranean diet and the DASH diet (Dietary Approaches to Stop Hypertension), the MIND diet stresses frequent consumption of vegetables – especially leafy greens – as well as nuts, berries, whole grains, fish, poultry, and wine or grape juice. In the large, nearly 5-year study of 923 subjects aged 58-98 years, the MIND diet was associated with significant gains in cognition – equivalent to a 7-year reversal of age. After 4.5 years, those who strictly adhered to the diet had a 53% reduction in risk for Alzheimer’s disease, and those who adhered moderately had a 35% reduction. And in a more recent Australian longitudinal study, the MIND diet was associated with a 53% reduced risk of cognitive impairment over 12 years.

Ketogenic diets also may exert a benefit. Theoretically, a state of ketosis forces the brain to burn ketones as an alternative fuel to glucose, thus boosting brain function in glucose-starved brains. A small pilot study with exploratory cognitive endpoints determined that diet-compliant subjects with mild to moderate Alzheimer’s experienced a mean 5-point improvement in the Alzheimer’s Disease Assessment Score–Cognition. They reverted to baseline scores within a month of ending the study.

Recent initial work into the gut microbiome provides some additional speculative, but interesting, data. A dysregulated microbiome can shift microbial populations toward a more inflammatory profile. Some work suggests that inflammatory cytokines then travel to the brain and induce a hyperresponse of neuron-damaging immune cells. A comprehensive review article discusses the complicated mechanisms that may be in play.

Play with your friends

Cognitive stimulation and social interaction also appear to modify dementia risk, although the data are a little more limited. But personal interaction is a key element of Dr. Baker’s ongoing EXERT trial.

The ongoing phase 3 trial randomized 300 adults with amnestic mild cognitive impairment to moderate to high intensity aerobic exercise plus one-on-one support at local YMCA gyms or a low-intensity stretching, balance, and range of motion program. In additional to cognitive testing, the trial includes brain imaging, cerebrospinal fluid sampling for biomarkers of Alzheimer’s disease, and a sleep study.

A key component is personal interaction with a trainer. “They spend a lot of one-on-one time with each person,” Dr. Baker said. “For me, that’s the crucial ingredient – that personal touch. It’s what helps people move from Point A to Point B in their behaviors.”

Virtual cognitive stimulation is also a burgeoning area of dementia prevention research right now. Numerous studies are ongoing to test whether virtual reality or other computer-based games might keep the mind sharp or even improve cognition in people at risk.
 

The power of three

If one lifestyle change can reduce dementia risk, what happens when all three work together?

That’s the newest question, first successfully explored in the mid-2000s, with the FINGER study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability). In FINGER, the triad of exercise, personal support at the gym, and a modified Mediterranean diet reduced Alzheimer’s disease risk and improved cognition relative to the control group.

FINGER showed that the intervention was feasible and that it was associated with cognitive preservation and reduced Alzheimer’s disease risk in a group of at-risk subjects. The active group also had a 25% greater improvement on a neuropsychological test battery relative to the control group. They also performed 150% better in processing speed, 83% better in executive function, and 40% better in short-term memory. They showed no increased risk of cognitive decline relative to the control group, which experienced a 30% increase in risk, according to lead investigator Miia Kivipelto, PhD, of the Karolinska Institute, Stockholm.

So successful was FINGER that it launched a global consortium of related studies called World Wide FINGERS. Active in six countries now, including the United States, the studies aim to discover whether such combinations of lifestyle interventions are workable across countries and cultures. World Wide FINGERS is largely supported by the Alzheimer’s Association.

Global enthusiasm for lifestyle interventions

In recognition of the importance of lifestyle changes for dementia prevention, the World Health Organization recently published “Risk reduction of cognitive decline and dementia.” The document reviews many studies and makes recommendations regarding not only exercise, diet, and cognitive stimulation, but also smoking and alcohol.

Research interest in these areas is surging, Dr. Baker said. “The [U.S.] National Institute on Aging now has 29 ongoing trials. There’s a strong commitment to investigations into how lifestyle interventions could protect brain health as we get older. Certainly, many fit and healthy people do develop Alzheimer’s. But for some, it could be medicine.”

But no matter how compliant people are, lifestyle changes will never completely rid the world of Alzheimer’s and other dementias. The view of Dr. Baker – and most other Alzheimer’s researchers – is to employ lifestyle changes to reduce risk as much as possible and not to stop when cognitive problems do present.

“We need to understand how lifestyle interventions might work in combination with pharmaceuticals,” she said. “If we can support the health of the body and the health of the mind, lifestyle interventions can be the fertilizer that would help drug therapy have its maximum effect.”

[email protected]

SAN DIEGO – To prevent dementia, follow Mom’s advice: Get up off the couch, go play with your friends, and eat your vegetables.

Michele G. Sullivan/MDedge News

After 15 years of disappointing drug trials, strong new evidence says the best way to attack Alzheimer’s disease is not to treat it once it develops, but to prevent it in the first place, Laura D. Baker, PhD, said at the Clinical Trials on Alzheimer’s Disease conference. Studies of exercise, cognitive and social stimulation, and diet show that each one can reduce the risk of dementia, and that a combination of all three may have even a more powerful and synergistic effect.

“We have become absolutely phobic of exercise,” said Dr. Baker of Wake Forest University, Winston-Salem, N.C. And it’s not just structured exercise we shirk. “We take the closest parking space, sit for hours on end, don’t even take the stairs. Yet we know from years of work that exercise has a powerful benefit on cardiovascular disease, lipid profiles, metabolic disease, stress, and mood. Now we are seeing that exercise also promotes brain health in normal aging and protects against cognitive decline and prevention.”
 

Get off the couch

The general benefits of exercise – chiefly aerobic exercise – are myriad, Dr. Baker said.

“Exercise increases effective neurorepair. It reduces oxidative stress. It improves insulin sensitivity and helps with maintaining normal weight. It reduces inflammation and increases normal clearance of amyloid-beta.”

A 2017 meta-analysis reviewed some of these findings. “The current review [of 16 studies] suggests that aerobic exercise may have positive effects on the right hippocampus and potentially beneficial effects on the overall and other parts of the hippocampus, the cingulate cortex, and the medial temporal areas. ... Moreover, aerobic exercise may increase functional connectivity or activation in the hippocampus, cingulate cortex, and parahippocampal gyrus regions,” wrote Mo-yi Li, PhD, of Fujian University of Traditional Chinese Medicine, Fuzhou, China, and colleagues.

Exercise increases brain-derived neurotrophic factor (BDNF), which in turn increases neuronal potentiation and synaptic plasticity. BDNF is also important in hippocampal neurogenesis; mice, after just one aerobic session, showed dramatic boosts in BDNF. A 2018 review elaborates on these findings.

Eat right

Diet mediates dementia risk through less direct, but very effective, pathways, Dr. Baker said. Diets rich in vegetables, berries, nuts, fish, lean proteins, and healthy fats improves virtually all metabolic measures. These, in turn, reduce the risk cerebrovascular disease – an important driver of vascular dementias and a contributor to Alzheimer’s disease risk as well.

The MIND diet study (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay), reported in 2015 was a very successful demonstration of this concept. A combination of the Mediterranean diet and the DASH diet (Dietary Approaches to Stop Hypertension), the MIND diet stresses frequent consumption of vegetables – especially leafy greens – as well as nuts, berries, whole grains, fish, poultry, and wine or grape juice. In the large, nearly 5-year study of 923 subjects aged 58-98 years, the MIND diet was associated with significant gains in cognition – equivalent to a 7-year reversal of age. After 4.5 years, those who strictly adhered to the diet had a 53% reduction in risk for Alzheimer’s disease, and those who adhered moderately had a 35% reduction. And in a more recent Australian longitudinal study, the MIND diet was associated with a 53% reduced risk of cognitive impairment over 12 years.

Ketogenic diets also may exert a benefit. Theoretically, a state of ketosis forces the brain to burn ketones as an alternative fuel to glucose, thus boosting brain function in glucose-starved brains. A small pilot study with exploratory cognitive endpoints determined that diet-compliant subjects with mild to moderate Alzheimer’s experienced a mean 5-point improvement in the Alzheimer’s Disease Assessment Score–Cognition. They reverted to baseline scores within a month of ending the study.

Recent initial work into the gut microbiome provides some additional speculative, but interesting, data. A dysregulated microbiome can shift microbial populations toward a more inflammatory profile. Some work suggests that inflammatory cytokines then travel to the brain and induce a hyperresponse of neuron-damaging immune cells. A comprehensive review article discusses the complicated mechanisms that may be in play.

Play with your friends

Cognitive stimulation and social interaction also appear to modify dementia risk, although the data are a little more limited. But personal interaction is a key element of Dr. Baker’s ongoing EXERT trial.

The ongoing phase 3 trial randomized 300 adults with amnestic mild cognitive impairment to moderate to high intensity aerobic exercise plus one-on-one support at local YMCA gyms or a low-intensity stretching, balance, and range of motion program. In additional to cognitive testing, the trial includes brain imaging, cerebrospinal fluid sampling for biomarkers of Alzheimer’s disease, and a sleep study.

A key component is personal interaction with a trainer. “They spend a lot of one-on-one time with each person,” Dr. Baker said. “For me, that’s the crucial ingredient – that personal touch. It’s what helps people move from Point A to Point B in their behaviors.”

Virtual cognitive stimulation is also a burgeoning area of dementia prevention research right now. Numerous studies are ongoing to test whether virtual reality or other computer-based games might keep the mind sharp or even improve cognition in people at risk.
 

The power of three

If one lifestyle change can reduce dementia risk, what happens when all three work together?

That’s the newest question, first successfully explored in the mid-2000s, with the FINGER study (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability). In FINGER, the triad of exercise, personal support at the gym, and a modified Mediterranean diet reduced Alzheimer’s disease risk and improved cognition relative to the control group.

FINGER showed that the intervention was feasible and that it was associated with cognitive preservation and reduced Alzheimer’s disease risk in a group of at-risk subjects. The active group also had a 25% greater improvement on a neuropsychological test battery relative to the control group. They also performed 150% better in processing speed, 83% better in executive function, and 40% better in short-term memory. They showed no increased risk of cognitive decline relative to the control group, which experienced a 30% increase in risk, according to lead investigator Miia Kivipelto, PhD, of the Karolinska Institute, Stockholm.

So successful was FINGER that it launched a global consortium of related studies called World Wide FINGERS. Active in six countries now, including the United States, the studies aim to discover whether such combinations of lifestyle interventions are workable across countries and cultures. World Wide FINGERS is largely supported by the Alzheimer’s Association.

Global enthusiasm for lifestyle interventions

In recognition of the importance of lifestyle changes for dementia prevention, the World Health Organization recently published “Risk reduction of cognitive decline and dementia.” The document reviews many studies and makes recommendations regarding not only exercise, diet, and cognitive stimulation, but also smoking and alcohol.

Research interest in these areas is surging, Dr. Baker said. “The [U.S.] National Institute on Aging now has 29 ongoing trials. There’s a strong commitment to investigations into how lifestyle interventions could protect brain health as we get older. Certainly, many fit and healthy people do develop Alzheimer’s. But for some, it could be medicine.”

But no matter how compliant people are, lifestyle changes will never completely rid the world of Alzheimer’s and other dementias. The view of Dr. Baker – and most other Alzheimer’s researchers – is to employ lifestyle changes to reduce risk as much as possible and not to stop when cognitive problems do present.

“We need to understand how lifestyle interventions might work in combination with pharmaceuticals,” she said. “If we can support the health of the body and the health of the mind, lifestyle interventions can be the fertilizer that would help drug therapy have its maximum effect.”

[email protected]

BALTIMORE – Candidates for epilepsy surgery who are employed are significantly more likely to decline surgery than are those who are unemployed, according to an analysis presented at the annual meeting of the American Epilepsy Society. “Future work should confirm this finding prospectively, determine if it holds in other patient populations, and explore the decision to proceed with or decline epilepsy surgery from a patient-centered perspective,” said Vishal Mandge, MD, MPH, a clinical neurophysiology fellow at Duke University in Durham, N.C., and colleagues. “Identifying the role that factors such as the fear of losing employment due to complications from surgery and inability to take medical leave for an extended period of time play in the patient’s decision to proceed with epilepsy surgery may identify needs and suggest strategies to reduce barriers to this underutilized treatment.”

Although epilepsy surgery is known to be safe and effective, many surgical candidates with drug-resistant epilepsy decline to undergo the procedure. Prior investigations of the barriers to epilepsy surgery have focused on access to epilepsy centers that offer epilepsy surgery and patients’ reluctance to undergo presurgical evaluation. Dr. Mandge and colleagues instead set out to evaluate the association between various demographic, disease-specific, and epilepsy-evaluation variables and patients’ decision to decline surgery after they have been identified as candidates.
 

A retrospective case-control study

The investigators conducted a retrospective case-control study of patients who were discussed at the epilepsy surgery conference of a tertiary care hospital serving an urban New York community between Jan. 1, 2009, and June 30, 2017. They identified patients who were considered candidates for resective epilepsy surgery. Dr. Mandge and colleagues used the chi-squared test for nominal variables and analysis of variance for scale variables to evaluate these variables’ associations with a patient’s decision to decline epilepsy surgery. They also performed multivariate binary logistic regression to identify variables that predict a patient’s decision to decline surgery.

Dr. Mandge and colleagues identified 159 patients who were discussed during the study period. Of this group, 87 patients were eligible for resective epilepsy surgery after a thorough evaluation. Thirty-four (40%) of the eligible patients declined to undergo surgery. Approximately 20% of eligible patients were employed, and 70% of patients had a high school diploma or higher education.

Univariate analysis indicated that employment (odds ratio, 4.2), temporal lesion on MRI (OR, 0.35), temporal EEG localization (OR, 0.21), and temporal seizure onset zone (OR, 0.19) were independently and significantly associated with a patient’s decision to decline surgery. Multivariate logistic regression analysis indicated that current employment (OR, 7.5), the number of current antiepileptic drugs (AEDs; OR, 3.5), and concordance between seizure semiology, seizure onset on EEG, and imaging (OR, 0.08) were significantly associated with a patient’s decision to decline surgery.
 

Fear of unemployment may explain results

“With each additional AED, the patients were 3.5 times more likely to decline surgery, even after adjusting for other variables,” said Alexis D. Boro, MD, a neurologist at Montefiore Medical Center in New York and one of the investigators. “My suspicion is that some of this reflects the burden of taking a lot of seizure medication. While the medications are much, much safer than seizures, and looking for and dealing with side effects is a lot of what we do, people often don’t feel great when they are taking multiple seizure medications. We counsel our patients that they should generally expect to stay on some seizure medications after surgery. The reason for surgery is to stop the seizures, not to stop the medications. We are often able to reduce medications after a period of time after surgery, and for many patients, this is one of the benefits.”

The association between employment and increased likelihood of declining surgery was unexpected and may not hold everywhere, said Dr. Boro. “We had expected the opposite result because we assumed that employed patients would be concerned that a seizure at work might result in loss of work. But it may be that many of our patients who are employed are concerned about losing their jobs if they miss work for a medical procedure. Some of our patients may be concerned about sharing medical information with their employers. For some of our patients, being employed may imply limited insurance coverage.”

The study was not supported by external funding, and the investigators did not report any disclosures.

[email protected]

SOURCE: Mandge VA et al. AES 2019, Abstract 1.362.

BALTIMORE – Candidates for epilepsy surgery who are employed are significantly more likely to decline surgery than are those who are unemployed, according to an analysis presented at the annual meeting of the American Epilepsy Society. “Future work should confirm this finding prospectively, determine if it holds in other patient populations, and explore the decision to proceed with or decline epilepsy surgery from a patient-centered perspective,” said Vishal Mandge, MD, MPH, a clinical neurophysiology fellow at Duke University in Durham, N.C., and colleagues. “Identifying the role that factors such as the fear of losing employment due to complications from surgery and inability to take medical leave for an extended period of time play in the patient’s decision to proceed with epilepsy surgery may identify needs and suggest strategies to reduce barriers to this underutilized treatment.”

Although epilepsy surgery is known to be safe and effective, many surgical candidates with drug-resistant epilepsy decline to undergo the procedure. Prior investigations of the barriers to epilepsy surgery have focused on access to epilepsy centers that offer epilepsy surgery and patients’ reluctance to undergo presurgical evaluation. Dr. Mandge and colleagues instead set out to evaluate the association between various demographic, disease-specific, and epilepsy-evaluation variables and patients’ decision to decline surgery after they have been identified as candidates.
 

A retrospective case-control study

The investigators conducted a retrospective case-control study of patients who were discussed at the epilepsy surgery conference of a tertiary care hospital serving an urban New York community between Jan. 1, 2009, and June 30, 2017. They identified patients who were considered candidates for resective epilepsy surgery. Dr. Mandge and colleagues used the chi-squared test for nominal variables and analysis of variance for scale variables to evaluate these variables’ associations with a patient’s decision to decline epilepsy surgery. They also performed multivariate binary logistic regression to identify variables that predict a patient’s decision to decline surgery.

Dr. Mandge and colleagues identified 159 patients who were discussed during the study period. Of this group, 87 patients were eligible for resective epilepsy surgery after a thorough evaluation. Thirty-four (40%) of the eligible patients declined to undergo surgery. Approximately 20% of eligible patients were employed, and 70% of patients had a high school diploma or higher education.

Univariate analysis indicated that employment (odds ratio, 4.2), temporal lesion on MRI (OR, 0.35), temporal EEG localization (OR, 0.21), and temporal seizure onset zone (OR, 0.19) were independently and significantly associated with a patient’s decision to decline surgery. Multivariate logistic regression analysis indicated that current employment (OR, 7.5), the number of current antiepileptic drugs (AEDs; OR, 3.5), and concordance between seizure semiology, seizure onset on EEG, and imaging (OR, 0.08) were significantly associated with a patient’s decision to decline surgery.
 

Fear of unemployment may explain results

“With each additional AED, the patients were 3.5 times more likely to decline surgery, even after adjusting for other variables,” said Alexis D. Boro, MD, a neurologist at Montefiore Medical Center in New York and one of the investigators. “My suspicion is that some of this reflects the burden of taking a lot of seizure medication. While the medications are much, much safer than seizures, and looking for and dealing with side effects is a lot of what we do, people often don’t feel great when they are taking multiple seizure medications. We counsel our patients that they should generally expect to stay on some seizure medications after surgery. The reason for surgery is to stop the seizures, not to stop the medications. We are often able to reduce medications after a period of time after surgery, and for many patients, this is one of the benefits.”

The association between employment and increased likelihood of declining surgery was unexpected and may not hold everywhere, said Dr. Boro. “We had expected the opposite result because we assumed that employed patients would be concerned that a seizure at work might result in loss of work. But it may be that many of our patients who are employed are concerned about losing their jobs if they miss work for a medical procedure. Some of our patients may be concerned about sharing medical information with their employers. For some of our patients, being employed may imply limited insurance coverage.”

The study was not supported by external funding, and the investigators did not report any disclosures.

[email protected]

SOURCE: Mandge VA et al. AES 2019, Abstract 1.362.

BALTIMORE – Candidates for epilepsy surgery who are employed are significantly more likely to decline surgery than are those who are unemployed, according to an analysis presented at the annual meeting of the American Epilepsy Society. “Future work should confirm this finding prospectively, determine if it holds in other patient populations, and explore the decision to proceed with or decline epilepsy surgery from a patient-centered perspective,” said Vishal Mandge, MD, MPH, a clinical neurophysiology fellow at Duke University in Durham, N.C., and colleagues. “Identifying the role that factors such as the fear of losing employment due to complications from surgery and inability to take medical leave for an extended period of time play in the patient’s decision to proceed with epilepsy surgery may identify needs and suggest strategies to reduce barriers to this underutilized treatment.”

Although epilepsy surgery is known to be safe and effective, many surgical candidates with drug-resistant epilepsy decline to undergo the procedure. Prior investigations of the barriers to epilepsy surgery have focused on access to epilepsy centers that offer epilepsy surgery and patients’ reluctance to undergo presurgical evaluation. Dr. Mandge and colleagues instead set out to evaluate the association between various demographic, disease-specific, and epilepsy-evaluation variables and patients’ decision to decline surgery after they have been identified as candidates.
 

A retrospective case-control study

The investigators conducted a retrospective case-control study of patients who were discussed at the epilepsy surgery conference of a tertiary care hospital serving an urban New York community between Jan. 1, 2009, and June 30, 2017. They identified patients who were considered candidates for resective epilepsy surgery. Dr. Mandge and colleagues used the chi-squared test for nominal variables and analysis of variance for scale variables to evaluate these variables’ associations with a patient’s decision to decline epilepsy surgery. They also performed multivariate binary logistic regression to identify variables that predict a patient’s decision to decline surgery.

Dr. Mandge and colleagues identified 159 patients who were discussed during the study period. Of this group, 87 patients were eligible for resective epilepsy surgery after a thorough evaluation. Thirty-four (40%) of the eligible patients declined to undergo surgery. Approximately 20% of eligible patients were employed, and 70% of patients had a high school diploma or higher education.

Univariate analysis indicated that employment (odds ratio, 4.2), temporal lesion on MRI (OR, 0.35), temporal EEG localization (OR, 0.21), and temporal seizure onset zone (OR, 0.19) were independently and significantly associated with a patient’s decision to decline surgery. Multivariate logistic regression analysis indicated that current employment (OR, 7.5), the number of current antiepileptic drugs (AEDs; OR, 3.5), and concordance between seizure semiology, seizure onset on EEG, and imaging (OR, 0.08) were significantly associated with a patient’s decision to decline surgery.
 

Fear of unemployment may explain results

“With each additional AED, the patients were 3.5 times more likely to decline surgery, even after adjusting for other variables,” said Alexis D. Boro, MD, a neurologist at Montefiore Medical Center in New York and one of the investigators. “My suspicion is that some of this reflects the burden of taking a lot of seizure medication. While the medications are much, much safer than seizures, and looking for and dealing with side effects is a lot of what we do, people often don’t feel great when they are taking multiple seizure medications. We counsel our patients that they should generally expect to stay on some seizure medications after surgery. The reason for surgery is to stop the seizures, not to stop the medications. We are often able to reduce medications after a period of time after surgery, and for many patients, this is one of the benefits.”

The association between employment and increased likelihood of declining surgery was unexpected and may not hold everywhere, said Dr. Boro. “We had expected the opposite result because we assumed that employed patients would be concerned that a seizure at work might result in loss of work. But it may be that many of our patients who are employed are concerned about losing their jobs if they miss work for a medical procedure. Some of our patients may be concerned about sharing medical information with their employers. For some of our patients, being employed may imply limited insurance coverage.”

The study was not supported by external funding, and the investigators did not report any disclosures.

[email protected]

SOURCE: Mandge VA et al. AES 2019, Abstract 1.362.

A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).

“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.

To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.

Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m² for women, 3.5 kg/m² for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m² or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.

Compared to individuals with BMI less than 25 kg/m² and a high level of physical activity, individuals with BMI at 25 kg/m² or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.

The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.

The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.

SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.

A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).

“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.

To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.

Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m² for women, 3.5 kg/m² for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m² or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.

Compared to individuals with BMI less than 25 kg/m² and a high level of physical activity, individuals with BMI at 25 kg/m² or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.

The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.

The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.

SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.

A new Norwegian study has identified a high body mass index and lower levels of physical activity as modifiable risk factors for developing psoriatic arthritis (PsA).

“Our study adds to the growing evidence that the risk of PsA is modifiable and highlights the importance of preventive work against obesity as well as encouraging physical activity in order to reduce the incidence of PsA,” wrote Ruth S. Thomsen, MD, of the Norwegian University of Science and Technology, and coauthors. The study was published in Arthritis Care & Research.

To determine the impact that adiposity and body fat distribution have on developing PsA, the researchers analyzed data from 36,626 women and men who participated in two surveys from the longitudinal, population-based Norwegian HUNT Study. All participants did not have diagnosed PsA at baseline in 1995-1997. Variables used in statistical analysis included calculated baseline BMI, waist circumference, waist-hip ratio, and level of physical activity.

Between baseline and follow-up in 2012, 185 new cases of PsA were reported. One standard deviation increase in BMI (4.2 kg/m² for women, 3.5 kg/m² for men) and waist circumstance (10.8 cm for women, 8.6 cm for men) was associated with adjusted hazard ratios of 1.40 (95% confidence interval, 1.24-1.58) and 1.48 (95% CI, 1.31-1.68), accordingly. Obese individuals – defined as BMI of 30 kg/m² or higher – had an adjusted HR of 2.46 (95% CI, 1.65-3.68) when compared with individuals at normal weight.

Compared to individuals with BMI less than 25 kg/m² and a high level of physical activity, individuals with BMI at 25 kg/m² or higher and any lower level of physical activity had an adjusted HR of 2.06 (95% CI, 1.18-3.58). In addition, individuals with a high waist circumference – defined as 81 cm or more in women and 95 cm or more in men – and low physical activity had an adjusted HR of 2.22 (95% CI, 1.37-3.58) in comparison to those with a high waist circumference and high physical activity (adjusted HR, 1.84; 95% CI, 0.97-3.47). Physical activity level was considered low with less than 3 hours of light physical activity and no hard physical activity per week and high with any amount of light activity plus 1 or more hours of hard physical activity.

The authors acknowledged the study’s potential limitations, including the requirement for participants to complete the final two HUNT study surveys and the use of stricter criteria than usual in validating PsA diagnoses.

The study was partially funded by a grant Dr. Thomsen received from the Norwegian Extra Foundation for Health and Rehabilitation. The authors reported no conflicts of interest.

SOURCE: Thomsen RS et al. Arthritis Care Res. 2019 Dec 7. doi: 10.1002/acr.24121.

ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.

Andrew D. Bowser/MDedge News

The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.

“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.

At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.

Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.

“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.

That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.

When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.

In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.

The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.

“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.

In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.

The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.

The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.

Dr. Anderson reported having no relevant conflicts of interest.

ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.

Andrew D. Bowser/MDedge News

The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.

“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.

At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.

Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.

“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.

That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.

When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.

In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.

The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.

“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.

In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.

The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.

The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.

Dr. Anderson reported having no relevant conflicts of interest.

ORLANDO – The latest American Society of Hematology guideline on venous thromboembolism (VTE) tackles 30 key questions regarding prophylaxis in hospitalized patients undergoing surgery, according to the chair of the guideline panel, who highlighted 9 of those questions during a special session at the society’s annual meeting.

Andrew D. Bowser/MDedge News

The clinical practice guideline, published just about a week before the annual meeting of the American Society of Hematology, focuses mainly on pharmacologic prophylaxis in specific surgical settings, said David R. Anderson, MD, dean of the faculty of medicine of Dalhousie University, Halifax, N.S.

“Our guidelines focused upon clinically important symptomatic outcomes, with less emphasis being placed on asymptomatic deep vein thrombosis detected by screening tests,” Dr. Anderson said.

At the special education session, Dr. Anderson highlighted several specific recommendations on prophylaxis in surgical patients.

Pharmacologic prophylaxis is not recommended for patients experiencing major trauma deemed to be at high risk of bleeding. Its use does reduce risk of symptomatic pulmonary embolism (PE) and deep vein thrombosis (DVT) by about 10 events per 1,000 patients treated; however, Dr. Anderson said, the panel’s opinion was that this benefit was outweighed by increased risk of major bleeding, at 24 events per 1,000 patients treated.

“We do recommend, however that this risk of bleeding must be reevaluated over the course of recovery of patients, and this may change the decision around this intervention over time,” Dr. Anderson told attendees at the special session.

That’s because pharmacologic prophylaxis is recommended in surgical patients at low to moderate risk of bleeding. In this scenario, the incremental risk of major bleeding (14 events per 1,000 patients treated) is outweighed by the benefit of the reduction of symptomatic VTE events, according to Dr. Anderson.

When pharmacologic prophylaxis is used, the panel recommends combined prophylaxis – mechanical prophylaxis in addition to pharmacologic prophylaxis – especially in those patients at high or very high risk of VTE. Evidence shows that the combination approach significantly reduces risk of PE, and strongly suggests it may also reduce risk of symptomatic proximal DVT, Dr. Anderson said.

In surgical patients not receiving pharmacologic prophylaxis, mechanical prophylaxis is recommended over no mechanical prophylaxis, he added. Moreover, in those patients receiving mechanical prophylaxis, the ASH panel recommends use of intermittent compression devices over graduated compression stockings.

The panel comes out against prophylactic inferior vena cava (IVC) filter insertion in the guidelines. Dr. Anderson said that the “small reduction” in PE risk seen in observational studies is outweighed by increased risk of DVT, and a resulting trend for increased mortality, associated with insertion of the devices.

“We did not consider other risks of IVC filters such as filter embolization or perforation, which again would be complications that would support our recommendation against routine use of these devices in patients undergoing major surgery,” he said.

In terms of the type of pharmacologic prophylaxis to use, the panel said low-molecular-weight heparin or unfractionated heparin would be reasonable choices in this setting. Available data do not demonstrate any significant differences between these choices for major clinical outcomes, Dr. Anderson added.

The guideline also addresses duration of pharmacologic prophylaxis, stating that extended prophylaxis – of at least 3 weeks – is favored over short-term prophylaxis, or up to 2 weeks of treatment. The extended approach significantly reduces risk of symptomatic PE and proximal DVT, though most of the supporting data come from studies of major joint arthroplasty and major general surgical procedures for patients with cancer. “We need more studies in other clinical areas to examine this particular question,” Dr. Anderson said.

The guideline on prophylaxis in surgical patients was published in Blood Advances (2019 Dec 3;3[23]:3898-944). Six other ASH VTE guidelines, all published in 2018, covered prophylaxis in medical patients, diagnosis, VTE in pregnancy, optimal anticoagulation, heparin-induced thrombocytopenia, and pediatric considerations. The guidelines are available on the ASH website.

Dr. Anderson reported having no relevant conflicts of interest.

A Food and Drug Administration advisory committee has voted 11 to 2 against a recommendation that the agency approve a long-studied antiarrhythmic agent for cardioversion of recent-onset atrial fibrillation (AFib).

It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.

Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.

Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.

Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.

“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.

The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”

FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.

In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.

For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.

Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.

Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.

In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”

As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.

Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.

“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.

Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.

“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.

“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.

“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”

Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.

“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.

But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.

The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.

If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”

The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.

Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.

Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.

This article first appeared on Medscape.com.

A Food and Drug Administration advisory committee has voted 11 to 2 against a recommendation that the agency approve a long-studied antiarrhythmic agent for cardioversion of recent-onset atrial fibrillation (AFib).

It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.

Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.

Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.

Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.

“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.

The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”

FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.

In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.

For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.

Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.

Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.

In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”

As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.

Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.

“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.

Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.

“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.

“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.

“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”

Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.

“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.

But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.

The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.

If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”

The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.

Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.

Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.

This article first appeared on Medscape.com.

A Food and Drug Administration advisory committee has voted 11 to 2 against a recommendation that the agency approve a long-studied antiarrhythmic agent for cardioversion of recent-onset atrial fibrillation (AFib).

It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.

Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.

Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.

Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.

“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.

The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”

FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.

In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.

For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.

Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.

Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.

In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”

As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.

Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.

“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.

Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.

“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.

“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.

“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”

Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.

“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.

But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.

The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.

If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”

The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.

Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.

Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.

This article first appeared on Medscape.com.

BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.

Jake Remaly/MDedge News

“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.

Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.

To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.

Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.

“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.

In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).

The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”

Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.

The researchers had no disclosures and reported receiving no outside funding for their work.

[email protected]

SOURCE: Patel UK et al. AES 2019, Abstract 2.140.

BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.

Jake Remaly/MDedge News

“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.

Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.

To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.

Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.

“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.

In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).

The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”

Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.

The researchers had no disclosures and reported receiving no outside funding for their work.

[email protected]

SOURCE: Patel UK et al. AES 2019, Abstract 2.140.

BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.

Jake Remaly/MDedge News

“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.

Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.

To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.

Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.

“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.

In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).

The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”

Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.

The researchers had no disclosures and reported receiving no outside funding for their work.

[email protected]

SOURCE: Patel UK et al. AES 2019, Abstract 2.140.

The Food and Drug Administration is investigating whether forms of the type 2 diabetes drug metformin that are available in the United States contain the genotoxic nitrosamine, N-nitrosodimethylamine (NDMA).

This follows reports of low-level NDMA contamination of metformin in other countries and of a few regulatory agencies issuing recalls for the drug, according to a statement from Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“There are no metformin recalls affecting the U.S. market at this time,” the agency emphasized in the statement. It said NDMA levels in affected medication have been low, at or even below the acceptable intake limit, and there is currently no evidence indicating that metformin drugs within the United States or European Union have been contaminated.

The FDA advised that patients should continue taking metformin alone or in combination with other drugs to control their diabetes and that it would be dangerous for them to stop taking the medication without first discussing it with their providers. It also recommended that providers continue to use metformin when “clinically appropriate” while the investigation is underway as there are no alternative therapies to treat the disease in the same way.

NDMA is a common contaminant that is found in water and some foods and has probable carcinogenic effects when exposure is too high. The acceptable daily intake for NDMA in the United States is 96 ng/day, according to the statement, though people who take in that amount or less every day for 70 years are not expected to have an increased risk of cancer.

Both the FDA and its counterpart, the European Medicines Agency, have recently investigated the presence of NDMA impurities in ranitidine, a drug used to reduce production of stomach acid, which led to several manufacturers issuing recalls for it.

The agencies have also investigated angiotensin II receptor blockers, which are used to treat hypertension, heart failure, and high blood pressure.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The presence of NDMA “can be related to the drug’s manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed,” Dr. Woodcock noted in the statement.

“We are monitoring this issue closely to assess any potential impact on patients with diabetes,” said Robert W. Lash, MD, chief professional and clinical affairs officer of the Endocrine Society. “We have members around the world and are concerned about the possibility of carcinogenic impurities in medications, both in the United States and elsewhere.”

[email protected]

The Food and Drug Administration is investigating whether forms of the type 2 diabetes drug metformin that are available in the United States contain the genotoxic nitrosamine, N-nitrosodimethylamine (NDMA).

This follows reports of low-level NDMA contamination of metformin in other countries and of a few regulatory agencies issuing recalls for the drug, according to a statement from Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“There are no metformin recalls affecting the U.S. market at this time,” the agency emphasized in the statement. It said NDMA levels in affected medication have been low, at or even below the acceptable intake limit, and there is currently no evidence indicating that metformin drugs within the United States or European Union have been contaminated.

The FDA advised that patients should continue taking metformin alone or in combination with other drugs to control their diabetes and that it would be dangerous for them to stop taking the medication without first discussing it with their providers. It also recommended that providers continue to use metformin when “clinically appropriate” while the investigation is underway as there are no alternative therapies to treat the disease in the same way.

NDMA is a common contaminant that is found in water and some foods and has probable carcinogenic effects when exposure is too high. The acceptable daily intake for NDMA in the United States is 96 ng/day, according to the statement, though people who take in that amount or less every day for 70 years are not expected to have an increased risk of cancer.

Both the FDA and its counterpart, the European Medicines Agency, have recently investigated the presence of NDMA impurities in ranitidine, a drug used to reduce production of stomach acid, which led to several manufacturers issuing recalls for it.

The agencies have also investigated angiotensin II receptor blockers, which are used to treat hypertension, heart failure, and high blood pressure.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The presence of NDMA “can be related to the drug’s manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed,” Dr. Woodcock noted in the statement.

“We are monitoring this issue closely to assess any potential impact on patients with diabetes,” said Robert W. Lash, MD, chief professional and clinical affairs officer of the Endocrine Society. “We have members around the world and are concerned about the possibility of carcinogenic impurities in medications, both in the United States and elsewhere.”

[email protected]

The Food and Drug Administration is investigating whether forms of the type 2 diabetes drug metformin that are available in the United States contain the genotoxic nitrosamine, N-nitrosodimethylamine (NDMA).

This follows reports of low-level NDMA contamination of metformin in other countries and of a few regulatory agencies issuing recalls for the drug, according to a statement from Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“There are no metformin recalls affecting the U.S. market at this time,” the agency emphasized in the statement. It said NDMA levels in affected medication have been low, at or even below the acceptable intake limit, and there is currently no evidence indicating that metformin drugs within the United States or European Union have been contaminated.

The FDA advised that patients should continue taking metformin alone or in combination with other drugs to control their diabetes and that it would be dangerous for them to stop taking the medication without first discussing it with their providers. It also recommended that providers continue to use metformin when “clinically appropriate” while the investigation is underway as there are no alternative therapies to treat the disease in the same way.

NDMA is a common contaminant that is found in water and some foods and has probable carcinogenic effects when exposure is too high. The acceptable daily intake for NDMA in the United States is 96 ng/day, according to the statement, though people who take in that amount or less every day for 70 years are not expected to have an increased risk of cancer.

Both the FDA and its counterpart, the European Medicines Agency, have recently investigated the presence of NDMA impurities in ranitidine, a drug used to reduce production of stomach acid, which led to several manufacturers issuing recalls for it.

The agencies have also investigated angiotensin II receptor blockers, which are used to treat hypertension, heart failure, and high blood pressure.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The presence of NDMA “can be related to the drug’s manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed,” Dr. Woodcock noted in the statement.

“We are monitoring this issue closely to assess any potential impact on patients with diabetes,” said Robert W. Lash, MD, chief professional and clinical affairs officer of the Endocrine Society. “We have members around the world and are concerned about the possibility of carcinogenic impurities in medications, both in the United States and elsewhere.”

[email protected]

Compromise bipartisan legislation to address surprise medical bills is getting push back from physician groups.

utah778/Thinkstock

Leadership from the House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions Committee on Dec. 9 unveiled a compromise bill that includes rate-setting for small surprise billing and arbitration for larger ones at a lower threshold than what was originally proposed.

The new bill, part of a broader Lower Health Care Costs Act, would protect patients from surprise medical bills related to emergency care, holding them responsible for in-network cost-sharing rates for out-of-network care provided at an in-network facility without their informed consent. Out-of-network surprise bills would be applied to the patient’s in-network deductible.

Under the legislation, providers would be paid at minimum the local, market-based median in-network negotiated rate for services, with a median rate under a $750 threshold. When the median exceeds $750, the provider or insurer would be allowed to choose arbitration process to resolve payment disputes.

The bill also protects patients by banning out-of-network facilities and providers from sending balance bills for more than in-network cost-sharing amounts.

Physician groups, however, see the legislation as a giveback to insurers that puts health care professionals at a disadvantage when negotiating to be included in insurer networks.

At issue is the $750 threshold for optional arbitration.

“If you set the arbitration system in such a way that limits the ability of a physician to go to arbitration to settle a dispute between a health plan and the doctor, and if you say that can only be done when there [are] bills that are greater than $750 for a particular service, then the vast majority of services provided by doctors will not be able to go to arbitration,” Christian Shalgian, director of advocacy and health policy at the American College of Surgeons, said in an interview.

Cynthia Moran, executive vice president of government relations and health policy at the American College of Radiology, agreed.

“This particular product is going in a direction that we’re not comfortable with so we can’t support it on the basis of the benchmarks and the independent dispute resolution (IDR) process with the $750 threshold,” she said in an interview. The services radiologists provide tend to be in the $100-200 range, she said, so that would automatically exclude them from accessing arbitration. She also said that it is her understanding that many physician services will fall under that $750 threshold.

“That $750 is really going to mean that the vast majority of this policy is a benchmark-driven policy,” she said. “It is not going to be an IDR-driven policy and that is the crux of our objection to it.”

And by taking arbitration off the table, insurers have no incentive to negotiate in good faith with doctors to ensure that doctors are getting paid for the services they perform.

“For those situations where there is an out-of-network physician at an in-network facility, we believe that the patient should not have to pay any more for those emergency situations where they patient doesn’t get to choose their doctor,” Mr. Shalgian said. “The dispute really comes down to how much does the health plan have to pay the doctor.”

He noted that the legislation ties the rate to median in-network rates “and that’s a problem for us as well because of the fact that [this is] going to allow the health plans to set median in-network rates as the rate that they can pay the doctors.”

If the bill becomes law, “when you have a situation where you have an in-network physician trying to negotiate with a health plan to stay in network, that health plan now has more power in that negotiation because if [the physician] is making more than median in-network rates, then the health plan can say, ‘go out of network because we will just pay you median in-network’ at that point. That is a significant concern to us as well.”

Mr. Shalgian said that the ideal solution would be to eliminate the threshold entirely and just send disputes to arbitration. Recognizing that it might not be practical, the $750 threshold should be lowered.

ACS supported a $300 threshold, he added.

The bill is expected to be tacked on to one of the mandatory spending bills that Congress needs to pass by the end of the year.

The $750 threshold would be a savings generator for the government and an important bill such as this should be passed on its own merits, Mr. Shalgian said.

Ms. Moran called for Congress to take its time with the legislation.

“We do think that this whole issue needs more time for everyone to understand what the impact is on this first run of the solution and we think it should be slowed down a bit,” she said. “It should not go to the floor until you hear more from the providers [after] the providers figure out what the impact will be.”

The American Medical Association also called for Congress to slow down.

“The current proposal relies on benchmark rate setting that would serve only to benefit the bottom line of insurance companies at the expense of patients seeking a robust network of physicians for their care,” AMA President Patrice Harris, MD, said in a statement. “Rather than rushing to meet arbitrary deadlines, it is important to get this legislation right.”

[email protected]

Compromise bipartisan legislation to address surprise medical bills is getting push back from physician groups.

utah778/Thinkstock

Leadership from the House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions Committee on Dec. 9 unveiled a compromise bill that includes rate-setting for small surprise billing and arbitration for larger ones at a lower threshold than what was originally proposed.

The new bill, part of a broader Lower Health Care Costs Act, would protect patients from surprise medical bills related to emergency care, holding them responsible for in-network cost-sharing rates for out-of-network care provided at an in-network facility without their informed consent. Out-of-network surprise bills would be applied to the patient’s in-network deductible.

Under the legislation, providers would be paid at minimum the local, market-based median in-network negotiated rate for services, with a median rate under a $750 threshold. When the median exceeds $750, the provider or insurer would be allowed to choose arbitration process to resolve payment disputes.

The bill also protects patients by banning out-of-network facilities and providers from sending balance bills for more than in-network cost-sharing amounts.

Physician groups, however, see the legislation as a giveback to insurers that puts health care professionals at a disadvantage when negotiating to be included in insurer networks.

At issue is the $750 threshold for optional arbitration.

“If you set the arbitration system in such a way that limits the ability of a physician to go to arbitration to settle a dispute between a health plan and the doctor, and if you say that can only be done when there [are] bills that are greater than $750 for a particular service, then the vast majority of services provided by doctors will not be able to go to arbitration,” Christian Shalgian, director of advocacy and health policy at the American College of Surgeons, said in an interview.

Cynthia Moran, executive vice president of government relations and health policy at the American College of Radiology, agreed.

“This particular product is going in a direction that we’re not comfortable with so we can’t support it on the basis of the benchmarks and the independent dispute resolution (IDR) process with the $750 threshold,” she said in an interview. The services radiologists provide tend to be in the $100-200 range, she said, so that would automatically exclude them from accessing arbitration. She also said that it is her understanding that many physician services will fall under that $750 threshold.

“That $750 is really going to mean that the vast majority of this policy is a benchmark-driven policy,” she said. “It is not going to be an IDR-driven policy and that is the crux of our objection to it.”

And by taking arbitration off the table, insurers have no incentive to negotiate in good faith with doctors to ensure that doctors are getting paid for the services they perform.

“For those situations where there is an out-of-network physician at an in-network facility, we believe that the patient should not have to pay any more for those emergency situations where they patient doesn’t get to choose their doctor,” Mr. Shalgian said. “The dispute really comes down to how much does the health plan have to pay the doctor.”

He noted that the legislation ties the rate to median in-network rates “and that’s a problem for us as well because of the fact that [this is] going to allow the health plans to set median in-network rates as the rate that they can pay the doctors.”

If the bill becomes law, “when you have a situation where you have an in-network physician trying to negotiate with a health plan to stay in network, that health plan now has more power in that negotiation because if [the physician] is making more than median in-network rates, then the health plan can say, ‘go out of network because we will just pay you median in-network’ at that point. That is a significant concern to us as well.”

Mr. Shalgian said that the ideal solution would be to eliminate the threshold entirely and just send disputes to arbitration. Recognizing that it might not be practical, the $750 threshold should be lowered.

ACS supported a $300 threshold, he added.

The bill is expected to be tacked on to one of the mandatory spending bills that Congress needs to pass by the end of the year.

The $750 threshold would be a savings generator for the government and an important bill such as this should be passed on its own merits, Mr. Shalgian said.

Ms. Moran called for Congress to take its time with the legislation.

“We do think that this whole issue needs more time for everyone to understand what the impact is on this first run of the solution and we think it should be slowed down a bit,” she said. “It should not go to the floor until you hear more from the providers [after] the providers figure out what the impact will be.”

The American Medical Association also called for Congress to slow down.

“The current proposal relies on benchmark rate setting that would serve only to benefit the bottom line of insurance companies at the expense of patients seeking a robust network of physicians for their care,” AMA President Patrice Harris, MD, said in a statement. “Rather than rushing to meet arbitrary deadlines, it is important to get this legislation right.”

[email protected]

Compromise bipartisan legislation to address surprise medical bills is getting push back from physician groups.

utah778/Thinkstock

Leadership from the House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions Committee on Dec. 9 unveiled a compromise bill that includes rate-setting for small surprise billing and arbitration for larger ones at a lower threshold than what was originally proposed.

The new bill, part of a broader Lower Health Care Costs Act, would protect patients from surprise medical bills related to emergency care, holding them responsible for in-network cost-sharing rates for out-of-network care provided at an in-network facility without their informed consent. Out-of-network surprise bills would be applied to the patient’s in-network deductible.

Under the legislation, providers would be paid at minimum the local, market-based median in-network negotiated rate for services, with a median rate under a $750 threshold. When the median exceeds $750, the provider or insurer would be allowed to choose arbitration process to resolve payment disputes.

The bill also protects patients by banning out-of-network facilities and providers from sending balance bills for more than in-network cost-sharing amounts.

Physician groups, however, see the legislation as a giveback to insurers that puts health care professionals at a disadvantage when negotiating to be included in insurer networks.

At issue is the $750 threshold for optional arbitration.

“If you set the arbitration system in such a way that limits the ability of a physician to go to arbitration to settle a dispute between a health plan and the doctor, and if you say that can only be done when there [are] bills that are greater than $750 for a particular service, then the vast majority of services provided by doctors will not be able to go to arbitration,” Christian Shalgian, director of advocacy and health policy at the American College of Surgeons, said in an interview.

Cynthia Moran, executive vice president of government relations and health policy at the American College of Radiology, agreed.

“This particular product is going in a direction that we’re not comfortable with so we can’t support it on the basis of the benchmarks and the independent dispute resolution (IDR) process with the $750 threshold,” she said in an interview. The services radiologists provide tend to be in the $100-200 range, she said, so that would automatically exclude them from accessing arbitration. She also said that it is her understanding that many physician services will fall under that $750 threshold.

“That $750 is really going to mean that the vast majority of this policy is a benchmark-driven policy,” she said. “It is not going to be an IDR-driven policy and that is the crux of our objection to it.”

And by taking arbitration off the table, insurers have no incentive to negotiate in good faith with doctors to ensure that doctors are getting paid for the services they perform.

“For those situations where there is an out-of-network physician at an in-network facility, we believe that the patient should not have to pay any more for those emergency situations where they patient doesn’t get to choose their doctor,” Mr. Shalgian said. “The dispute really comes down to how much does the health plan have to pay the doctor.”

He noted that the legislation ties the rate to median in-network rates “and that’s a problem for us as well because of the fact that [this is] going to allow the health plans to set median in-network rates as the rate that they can pay the doctors.”

If the bill becomes law, “when you have a situation where you have an in-network physician trying to negotiate with a health plan to stay in network, that health plan now has more power in that negotiation because if [the physician] is making more than median in-network rates, then the health plan can say, ‘go out of network because we will just pay you median in-network’ at that point. That is a significant concern to us as well.”

Mr. Shalgian said that the ideal solution would be to eliminate the threshold entirely and just send disputes to arbitration. Recognizing that it might not be practical, the $750 threshold should be lowered.

ACS supported a $300 threshold, he added.

The bill is expected to be tacked on to one of the mandatory spending bills that Congress needs to pass by the end of the year.

The $750 threshold would be a savings generator for the government and an important bill such as this should be passed on its own merits, Mr. Shalgian said.

Ms. Moran called for Congress to take its time with the legislation.

“We do think that this whole issue needs more time for everyone to understand what the impact is on this first run of the solution and we think it should be slowed down a bit,” she said. “It should not go to the floor until you hear more from the providers [after] the providers figure out what the impact will be.”

The American Medical Association also called for Congress to slow down.

“The current proposal relies on benchmark rate setting that would serve only to benefit the bottom line of insurance companies at the expense of patients seeking a robust network of physicians for their care,” AMA President Patrice Harris, MD, said in a statement. “Rather than rushing to meet arbitrary deadlines, it is important to get this legislation right.”

[email protected]

SAN ANTONIO – The American Cancer Society’s 2018 qualified recommendation to lower the starting age for colorectal cancer screening from 50 to 45 years in average-risk individuals has picked up new support from a New Hampshire Colonoscopy Registry analysis.

Data from the population-based statewide colonoscopy registry demonstrated that the prevalence of both advanced adenomas and clinically significant serrated polyps was closely similar for average-risk New Hampshirites age 45-49 years and for those age 50-54, Lynn F. Butterly, MD, reported at the annual meeting of the American College of Gastroenterology.

“The clinical implication is that our data support the recommendation to begin average-risk colorectal cancer screening at age 45,” declared Dr. Butterly, a gastroenterologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

The American Cancer Society recommendation to lower the initial screening age was designed to address a disturbing national trend: the climbing incidence of colorectal cancer in young adults. Indeed, the incidence increased by 55% among 20- to 49-year-olds during 1995-2016, even while falling by 38% in individuals age 50 years and older. The 2018 recommendation was billed as “qualified” because it was based upon predictive modeling and National Cancer Institute Surveillance, Epidemiology, and End Results data which have been criticized as subject to potential bias. Several studies conducted in Korea and other Asian countries have reported a lower colorectal cancer risk in the younger adult population than in those age 50 or older, but questions have been raised about the applicability of such data to the U.S. population.

For Dr. Butterly and coinvestigators, the research imperative was clear: “We need to generate U.S. outcomes data for average-risk individuals age 45-49, versus those over age 50, for whom colorectal cancer screening is already strongly recommended.”

Toward that end, the investigators turned to the New Hampshire Colonoscopy Registry, which contains detailed data on 200,000 colonoscopies, with some 400 variables recorded per patient. To zero in on an average-risk population below age 50, they restricted the analysis to patients undergoing their first colonoscopy for evaluation of low-risk conditions including abdominal pain or constipation while excluding those with GI bleeding, iron-deficiency anemia, abnormal imaging, or a family history of colorectal cancer.

The final study population included 42,600 New Hampshire residents who underwent their first colonoscopy. The key outcomes were the prevalence of advanced adenomas, defined as adenomas more than 1 cm in size, or with high-grade dysplasia or villous elements, and the prevalence of clinically significant serrated polyps larger than 1 cm, or larger than 5 mm if proximally located, as well as traditional serrated adenomas and those with sessile features.

The prevalence of advanced adenomas in 1,870 average-risk patients aged 45-49 years was 3.7% and nearly identical at 3.6% in 22,160 individuals undergoing screening colonoscopy at age 50-54. The rate of clinically significant serrated polyps was 5.9% in the 45- to 49-year-olds, closely similar to the 6.1% rate in patients age 50-54.

Of note, the prevalence of advanced adenomas was just 1.1% in individuals younger than age 40 years, jumping to 3.0% among 40- to 44-year-olds, 5.1% in those age 55-59, and 6.9% at age 60 or more. Clinically significant serrated polyps followed a similar pattern, with rates of 3.0% before age 40, 5.1% in 40- to 44-year-olds, 6.6% in 55- to 59-year-olds, and 6.0% in those who were older.

In a multivariate logistic regression analysis adjusted for sex, body mass index, smoking, and other potential confounders, 45- to 49-year-olds were at a 243% increased risk of finding advanced adenomas on colonoscopy, compared with those less than 40 years old, while the 50- to 54-year-olds had a virtually identical 244% increased risk.

Dr. Butterly noted that there are now 15,000 cases of colorectal cancer occurring annually in individuals under age 50 in the United States, with 3,600 deaths.

“Prevention of colorectal cancer in young, productive individuals is an essential clinical imperative that must be addressed,” she concluded.

She reported having no financial conflicts regarding her study.

[email protected]

SAN ANTONIO – The American Cancer Society’s 2018 qualified recommendation to lower the starting age for colorectal cancer screening from 50 to 45 years in average-risk individuals has picked up new support from a New Hampshire Colonoscopy Registry analysis.

Data from the population-based statewide colonoscopy registry demonstrated that the prevalence of both advanced adenomas and clinically significant serrated polyps was closely similar for average-risk New Hampshirites age 45-49 years and for those age 50-54, Lynn F. Butterly, MD, reported at the annual meeting of the American College of Gastroenterology.

“The clinical implication is that our data support the recommendation to begin average-risk colorectal cancer screening at age 45,” declared Dr. Butterly, a gastroenterologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

The American Cancer Society recommendation to lower the initial screening age was designed to address a disturbing national trend: the climbing incidence of colorectal cancer in young adults. Indeed, the incidence increased by 55% among 20- to 49-year-olds during 1995-2016, even while falling by 38% in individuals age 50 years and older. The 2018 recommendation was billed as “qualified” because it was based upon predictive modeling and National Cancer Institute Surveillance, Epidemiology, and End Results data which have been criticized as subject to potential bias. Several studies conducted in Korea and other Asian countries have reported a lower colorectal cancer risk in the younger adult population than in those age 50 or older, but questions have been raised about the applicability of such data to the U.S. population.

For Dr. Butterly and coinvestigators, the research imperative was clear: “We need to generate U.S. outcomes data for average-risk individuals age 45-49, versus those over age 50, for whom colorectal cancer screening is already strongly recommended.”

Toward that end, the investigators turned to the New Hampshire Colonoscopy Registry, which contains detailed data on 200,000 colonoscopies, with some 400 variables recorded per patient. To zero in on an average-risk population below age 50, they restricted the analysis to patients undergoing their first colonoscopy for evaluation of low-risk conditions including abdominal pain or constipation while excluding those with GI bleeding, iron-deficiency anemia, abnormal imaging, or a family history of colorectal cancer.

The final study population included 42,600 New Hampshire residents who underwent their first colonoscopy. The key outcomes were the prevalence of advanced adenomas, defined as adenomas more than 1 cm in size, or with high-grade dysplasia or villous elements, and the prevalence of clinically significant serrated polyps larger than 1 cm, or larger than 5 mm if proximally located, as well as traditional serrated adenomas and those with sessile features.

The prevalence of advanced adenomas in 1,870 average-risk patients aged 45-49 years was 3.7% and nearly identical at 3.6% in 22,160 individuals undergoing screening colonoscopy at age 50-54. The rate of clinically significant serrated polyps was 5.9% in the 45- to 49-year-olds, closely similar to the 6.1% rate in patients age 50-54.

Of note, the prevalence of advanced adenomas was just 1.1% in individuals younger than age 40 years, jumping to 3.0% among 40- to 44-year-olds, 5.1% in those age 55-59, and 6.9% at age 60 or more. Clinically significant serrated polyps followed a similar pattern, with rates of 3.0% before age 40, 5.1% in 40- to 44-year-olds, 6.6% in 55- to 59-year-olds, and 6.0% in those who were older.

In a multivariate logistic regression analysis adjusted for sex, body mass index, smoking, and other potential confounders, 45- to 49-year-olds were at a 243% increased risk of finding advanced adenomas on colonoscopy, compared with those less than 40 years old, while the 50- to 54-year-olds had a virtually identical 244% increased risk.

Dr. Butterly noted that there are now 15,000 cases of colorectal cancer occurring annually in individuals under age 50 in the United States, with 3,600 deaths.

“Prevention of colorectal cancer in young, productive individuals is an essential clinical imperative that must be addressed,” she concluded.

She reported having no financial conflicts regarding her study.

[email protected]

SAN ANTONIO – The American Cancer Society’s 2018 qualified recommendation to lower the starting age for colorectal cancer screening from 50 to 45 years in average-risk individuals has picked up new support from a New Hampshire Colonoscopy Registry analysis.

Data from the population-based statewide colonoscopy registry demonstrated that the prevalence of both advanced adenomas and clinically significant serrated polyps was closely similar for average-risk New Hampshirites age 45-49 years and for those age 50-54, Lynn F. Butterly, MD, reported at the annual meeting of the American College of Gastroenterology.

“The clinical implication is that our data support the recommendation to begin average-risk colorectal cancer screening at age 45,” declared Dr. Butterly, a gastroenterologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

The American Cancer Society recommendation to lower the initial screening age was designed to address a disturbing national trend: the climbing incidence of colorectal cancer in young adults. Indeed, the incidence increased by 55% among 20- to 49-year-olds during 1995-2016, even while falling by 38% in individuals age 50 years and older. The 2018 recommendation was billed as “qualified” because it was based upon predictive modeling and National Cancer Institute Surveillance, Epidemiology, and End Results data which have been criticized as subject to potential bias. Several studies conducted in Korea and other Asian countries have reported a lower colorectal cancer risk in the younger adult population than in those age 50 or older, but questions have been raised about the applicability of such data to the U.S. population.

For Dr. Butterly and coinvestigators, the research imperative was clear: “We need to generate U.S. outcomes data for average-risk individuals age 45-49, versus those over age 50, for whom colorectal cancer screening is already strongly recommended.”

Toward that end, the investigators turned to the New Hampshire Colonoscopy Registry, which contains detailed data on 200,000 colonoscopies, with some 400 variables recorded per patient. To zero in on an average-risk population below age 50, they restricted the analysis to patients undergoing their first colonoscopy for evaluation of low-risk conditions including abdominal pain or constipation while excluding those with GI bleeding, iron-deficiency anemia, abnormal imaging, or a family history of colorectal cancer.

The final study population included 42,600 New Hampshire residents who underwent their first colonoscopy. The key outcomes were the prevalence of advanced adenomas, defined as adenomas more than 1 cm in size, or with high-grade dysplasia or villous elements, and the prevalence of clinically significant serrated polyps larger than 1 cm, or larger than 5 mm if proximally located, as well as traditional serrated adenomas and those with sessile features.

The prevalence of advanced adenomas in 1,870 average-risk patients aged 45-49 years was 3.7% and nearly identical at 3.6% in 22,160 individuals undergoing screening colonoscopy at age 50-54. The rate of clinically significant serrated polyps was 5.9% in the 45- to 49-year-olds, closely similar to the 6.1% rate in patients age 50-54.

Of note, the prevalence of advanced adenomas was just 1.1% in individuals younger than age 40 years, jumping to 3.0% among 40- to 44-year-olds, 5.1% in those age 55-59, and 6.9% at age 60 or more. Clinically significant serrated polyps followed a similar pattern, with rates of 3.0% before age 40, 5.1% in 40- to 44-year-olds, 6.6% in 55- to 59-year-olds, and 6.0% in those who were older.

In a multivariate logistic regression analysis adjusted for sex, body mass index, smoking, and other potential confounders, 45- to 49-year-olds were at a 243% increased risk of finding advanced adenomas on colonoscopy, compared with those less than 40 years old, while the 50- to 54-year-olds had a virtually identical 244% increased risk.

Dr. Butterly noted that there are now 15,000 cases of colorectal cancer occurring annually in individuals under age 50 in the United States, with 3,600 deaths.

“Prevention of colorectal cancer in young, productive individuals is an essential clinical imperative that must be addressed,” she concluded.

She reported having no financial conflicts regarding her study.

[email protected]

PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.

Mitchel L. Zoler/MDedge News

Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.

This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.

Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m² or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m².

During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.

[email protected]

SOURCE: Ardissino M. AHA 2019, Abstract 335.

PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.

Mitchel L. Zoler/MDedge News

Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.

This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.

Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m² or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m².

During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.

[email protected]

SOURCE: Ardissino M. AHA 2019, Abstract 335.

PHILADELPHIA – Obese people living in the United Kingdom who underwent bariatric surgery had a two-thirds lower rate of major cerebrovascular events than that of a matched group of obese residents who did not undergo bariatric surgery, in a retrospective study of 8,424 people followed for a mean of just over 11 years.

Mitchel L. Zoler/MDedge News

Although the cut in cerebrovascular events that linked with bariatric surgery shown by the analysis was mostly driven by a reduced rate of transient ischemic attacks, a potentially unreliable diagnosis, the results showed consistent reductions in the rates of acute ischemic strokes as well as in acute, nontraumatic intracranial hemorrhages, two other components of the combined primary endpoint, Maddalena Ardissino, MBBS, said at the American Heart Association scientific sessions.

This finding of an apparent benefit from bariatric surgery in obese patients in a large U.K. database confirms other findings from a “fast-growing” evidence base showing benefits from bariatric surgery for reducing other types of cardiovascular disease events, said Dr. Ardissino, a researcher at Imperial College, London. However, the impact of bariatric surgery specifically on cerebrovascular events had not received much attention in published studies, she noted.

Her study used data collected by the Clinical Practice Research Datalink, which has primary and secondary care health records for about 42 million U.K. residents. The researchers focused on more than 251,000 obese U.K. adults (body mass index of 30 kg/m² or greater) without a history of a cerebrovascular event who had at least 1 year of follow-up, a data file that included 4,212 adults who had undergone bariatric surgery. Their analysis matched these surgical patients with an equal number of obese adults who did not have surgery, pairing the cases and controls based on age, sex, and BMI. The resulting matched cohorts each averaged 50 years old, with a mean BMI of 40.5 kg/m².

During just over 11 years of average follow-up, the incidence of acute ischemic stroke, acute intracranial hemorrhage, subarachnoid hemorrhage, or transient ischemic attack was about 1.3% in those without bariatric surgery and about 0.4% in those who had surgery, an absolute risk reduction of 0.9 linked with surgery and a relative risk reduction of 65% that was statistically significant, Dr. Ardissino reported. All-cause mortality was about 70% lower in the group that underwent bariatric surgery compared with those who did not have surgery, a finding that confirmed prior reports. She cautioned that the analysis was limited by a relatively low number of total events, and by the small number of criteria used for cohort matching that might have left unadjusted certain potential confounders such as the level of engagement people had with their medical care.

[email protected]

SOURCE: Ardissino M. AHA 2019, Abstract 335.