Literature Review

Poor physical performance was linked with an increased risk of dementia in a study of individuals age 90 and older who were followed for an average of 2.6 years. After controlling for various factors, poor standing balance had the strongest association with dementia, followed by poor performance in a four-meter walk test and a handgrip test. The study findings were published online ahead of print July 5 in the Journal of the American Geriatrics Society.

“The oldest old, people aged 90 and older, represent the fastest-growing segment of society with the highest rates of dementia; however, many of the traditional risk factors of dementia lose or change their effect in this age group. Therefore, it is crucial that we identify age-specific risk and protective factors for late-age dementia,” said lead author Szofia S. Bullain, MD, an Assistant Professor of Neurology at the University of California, Irvine. “The fact that we were able to detect impairment in physical performance two to three years before the onset of dementia suggests that poor physical performance may be a risk factor for, or an early sign of, developing late-age dementia.”

Dr. Bullain and colleagues conducted a population-based, longitudinal study to examine the relationship between physical performance and dementia in individuals age 90 and older without dementia. They enrolled 176 men and 402 women without dementia from the 90+ Study. Among the total cohort of 578, the mean age was 93.3. At baseline, 54% of the participants were cognitively normal, and 46% had cognitive impairment, but no dementia.

Szofia S. Bullain, MD

Physical performance measures included a four-meter walk, five chair stands, handgrip, and standing balance. Measures were scored from zero (unable to perform) to four (best performance). The outcome was dementia, diagnosed according to DSM-IV criteria. Hazard ratios (HRs) for dementia in relation to baseline physical performance were estimated using Cox regression after adjustment for potential confounders.

Poor physical performance in most measures was associated with greater risk of incident dementia over a mean follow-up of 2.6 years (range, seven months to nine years). After controlling for potential confounders, standing balance had the strongest association with incident dementia (HR, 1.9 to 2.5), followed by four-meter walk (HR, 1.1 to 1.8) and handgrip (HR, 1.0 to 2.0). The association with five chair stands was not significant.

The researchers next plan to examine the underlying pathologic processes, which may provide clues to new preventive and treatment strategies for late-age dementia.

—Glenn S. Williams

Poor physical performance was linked with an increased risk of dementia in a study of individuals age 90 and older who were followed for an average of 2.6 years. After controlling for various factors, poor standing balance had the strongest association with dementia, followed by poor performance in a four-meter walk test and a handgrip test. The study findings were published online ahead of print July 5 in the Journal of the American Geriatrics Society.

“The oldest old, people aged 90 and older, represent the fastest-growing segment of society with the highest rates of dementia; however, many of the traditional risk factors of dementia lose or change their effect in this age group. Therefore, it is crucial that we identify age-specific risk and protective factors for late-age dementia,” said lead author Szofia S. Bullain, MD, an Assistant Professor of Neurology at the University of California, Irvine. “The fact that we were able to detect impairment in physical performance two to three years before the onset of dementia suggests that poor physical performance may be a risk factor for, or an early sign of, developing late-age dementia.”

Dr. Bullain and colleagues conducted a population-based, longitudinal study to examine the relationship between physical performance and dementia in individuals age 90 and older without dementia. They enrolled 176 men and 402 women without dementia from the 90+ Study. Among the total cohort of 578, the mean age was 93.3. At baseline, 54% of the participants were cognitively normal, and 46% had cognitive impairment, but no dementia.

Szofia S. Bullain, MD

Physical performance measures included a four-meter walk, five chair stands, handgrip, and standing balance. Measures were scored from zero (unable to perform) to four (best performance). The outcome was dementia, diagnosed according to DSM-IV criteria. Hazard ratios (HRs) for dementia in relation to baseline physical performance were estimated using Cox regression after adjustment for potential confounders.

Poor physical performance in most measures was associated with greater risk of incident dementia over a mean follow-up of 2.6 years (range, seven months to nine years). After controlling for potential confounders, standing balance had the strongest association with incident dementia (HR, 1.9 to 2.5), followed by four-meter walk (HR, 1.1 to 1.8) and handgrip (HR, 1.0 to 2.0). The association with five chair stands was not significant.

The researchers next plan to examine the underlying pathologic processes, which may provide clues to new preventive and treatment strategies for late-age dementia.

—Glenn S. Williams

Poor physical performance was linked with an increased risk of dementia in a study of individuals age 90 and older who were followed for an average of 2.6 years. After controlling for various factors, poor standing balance had the strongest association with dementia, followed by poor performance in a four-meter walk test and a handgrip test. The study findings were published online ahead of print July 5 in the Journal of the American Geriatrics Society.

“The oldest old, people aged 90 and older, represent the fastest-growing segment of society with the highest rates of dementia; however, many of the traditional risk factors of dementia lose or change their effect in this age group. Therefore, it is crucial that we identify age-specific risk and protective factors for late-age dementia,” said lead author Szofia S. Bullain, MD, an Assistant Professor of Neurology at the University of California, Irvine. “The fact that we were able to detect impairment in physical performance two to three years before the onset of dementia suggests that poor physical performance may be a risk factor for, or an early sign of, developing late-age dementia.”

Dr. Bullain and colleagues conducted a population-based, longitudinal study to examine the relationship between physical performance and dementia in individuals age 90 and older without dementia. They enrolled 176 men and 402 women without dementia from the 90+ Study. Among the total cohort of 578, the mean age was 93.3. At baseline, 54% of the participants were cognitively normal, and 46% had cognitive impairment, but no dementia.

Szofia S. Bullain, MD

Physical performance measures included a four-meter walk, five chair stands, handgrip, and standing balance. Measures were scored from zero (unable to perform) to four (best performance). The outcome was dementia, diagnosed according to DSM-IV criteria. Hazard ratios (HRs) for dementia in relation to baseline physical performance were estimated using Cox regression after adjustment for potential confounders.

Poor physical performance in most measures was associated with greater risk of incident dementia over a mean follow-up of 2.6 years (range, seven months to nine years). After controlling for potential confounders, standing balance had the strongest association with incident dementia (HR, 1.9 to 2.5), followed by four-meter walk (HR, 1.1 to 1.8) and handgrip (HR, 1.0 to 2.0). The association with five chair stands was not significant.

The researchers next plan to examine the underlying pathologic processes, which may provide clues to new preventive and treatment strategies for late-age dementia.

—Glenn S. Williams

Aspirin may substantially reduce the risk of recurrent stroke when used immediately after a transient ischemic attack (TIA), according to a study published online ahead of print May 18 in the Lancet. Aspirin appears to reduce the risk of disabling stroke to a greater extent than it reduces the risk of nondisabling stroke. This finding suggests that aspirin has a neuroprotective effect, researchers said.

“The risk of major stroke is very high for only the first few days after TIA and minor ischemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials,” said Peter M. Rothwell, MD, PhD, Action Research Professor of Neurology at the University of Oxford, UK, and his colleagues.

Previous studies of patients with acute stroke have found that aspirin reduced the risk of recurrent stroke by 13%, but the effect of aspirin on the risk of recurrence after TIA had not been reported. Researchers hypothesized that short-term benefits of early aspirin had been underestimated. To test this hypothesis, Dr. Rothwell and his colleagues examined the time course of the effects of aspirin and dipyridamole, and studied the risk and severity of recurrent ischemic stroke following aspirin treatment. In addition, investigators compared the severity of early recurrent strokes between treatment groups. The effect of aspirin and dipyridamole in secondary prevention of stroke was also observed.

The investigators pooled data for 15,778 participants in 12 trials of aspirin versus control in secondary prevention. Patients were randomized less than 48 hours after a major acute stroke. They also obtained data on the nature and timing of the following outcome variables: recurrent stroke, recurrent ischemic stroke, acute myocardial infarction, intracerebral hemorrhage, fatal extracranial bleeding, and other causes of death. Data were also obtained on the severity and outcome of all recurrent strokes. In addition, researchers gathered individual data on severity of stroke at study entry. The researchers classified recurrent stroke according to the following three time periods: less than six weeks, six to 12 weeks, and more than 12 weeks after randomization.

Aspirin reduced the six-week risk of recurrent ischemic stroke by about 60%. The benefit of aspirin was greatest during the first two weeks, but further benefit accrued up to 12 weeks. Aspirin also decreased the risk of a fatal or disabling stroke by 70% to 80% over the first few days and weeks. Data suggested that administering dipyridamole plus aspirin versus aspirin alone had no impact on the risk or severity of recurrent ischemic stroke within 12 weeks. One fatal extracranial bleed within 12 weeks of randomization was reported. Aspirin did not reduce the severity of recurrent stroke that occurred at 12 or more weeks after TIA.

“Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identifies aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA,” the researchers said.

Some limitations of this study include the time period of the trials (the 1980s and 1990s), since medical care has changed since then, and more detailed investigation and intensive lowering of blood pressure and lipids are now possible, the researchers said.

—Erica Robinson

Aspirin may substantially reduce the risk of recurrent stroke when used immediately after a transient ischemic attack (TIA), according to a study published online ahead of print May 18 in the Lancet. Aspirin appears to reduce the risk of disabling stroke to a greater extent than it reduces the risk of nondisabling stroke. This finding suggests that aspirin has a neuroprotective effect, researchers said.

“The risk of major stroke is very high for only the first few days after TIA and minor ischemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials,” said Peter M. Rothwell, MD, PhD, Action Research Professor of Neurology at the University of Oxford, UK, and his colleagues.

Previous studies of patients with acute stroke have found that aspirin reduced the risk of recurrent stroke by 13%, but the effect of aspirin on the risk of recurrence after TIA had not been reported. Researchers hypothesized that short-term benefits of early aspirin had been underestimated. To test this hypothesis, Dr. Rothwell and his colleagues examined the time course of the effects of aspirin and dipyridamole, and studied the risk and severity of recurrent ischemic stroke following aspirin treatment. In addition, investigators compared the severity of early recurrent strokes between treatment groups. The effect of aspirin and dipyridamole in secondary prevention of stroke was also observed.

The investigators pooled data for 15,778 participants in 12 trials of aspirin versus control in secondary prevention. Patients were randomized less than 48 hours after a major acute stroke. They also obtained data on the nature and timing of the following outcome variables: recurrent stroke, recurrent ischemic stroke, acute myocardial infarction, intracerebral hemorrhage, fatal extracranial bleeding, and other causes of death. Data were also obtained on the severity and outcome of all recurrent strokes. In addition, researchers gathered individual data on severity of stroke at study entry. The researchers classified recurrent stroke according to the following three time periods: less than six weeks, six to 12 weeks, and more than 12 weeks after randomization.

Aspirin reduced the six-week risk of recurrent ischemic stroke by about 60%. The benefit of aspirin was greatest during the first two weeks, but further benefit accrued up to 12 weeks. Aspirin also decreased the risk of a fatal or disabling stroke by 70% to 80% over the first few days and weeks. Data suggested that administering dipyridamole plus aspirin versus aspirin alone had no impact on the risk or severity of recurrent ischemic stroke within 12 weeks. One fatal extracranial bleed within 12 weeks of randomization was reported. Aspirin did not reduce the severity of recurrent stroke that occurred at 12 or more weeks after TIA.

“Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identifies aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA,” the researchers said.

Some limitations of this study include the time period of the trials (the 1980s and 1990s), since medical care has changed since then, and more detailed investigation and intensive lowering of blood pressure and lipids are now possible, the researchers said.

—Erica Robinson

Aspirin may substantially reduce the risk of recurrent stroke when used immediately after a transient ischemic attack (TIA), according to a study published online ahead of print May 18 in the Lancet. Aspirin appears to reduce the risk of disabling stroke to a greater extent than it reduces the risk of nondisabling stroke. This finding suggests that aspirin has a neuroprotective effect, researchers said.

“The risk of major stroke is very high for only the first few days after TIA and minor ischemic stroke, and observational studies show substantially greater benefits of early medical treatment in the acute phase than do longer-term trials,” said Peter M. Rothwell, MD, PhD, Action Research Professor of Neurology at the University of Oxford, UK, and his colleagues.

Previous studies of patients with acute stroke have found that aspirin reduced the risk of recurrent stroke by 13%, but the effect of aspirin on the risk of recurrence after TIA had not been reported. Researchers hypothesized that short-term benefits of early aspirin had been underestimated. To test this hypothesis, Dr. Rothwell and his colleagues examined the time course of the effects of aspirin and dipyridamole, and studied the risk and severity of recurrent ischemic stroke following aspirin treatment. In addition, investigators compared the severity of early recurrent strokes between treatment groups. The effect of aspirin and dipyridamole in secondary prevention of stroke was also observed.

The investigators pooled data for 15,778 participants in 12 trials of aspirin versus control in secondary prevention. Patients were randomized less than 48 hours after a major acute stroke. They also obtained data on the nature and timing of the following outcome variables: recurrent stroke, recurrent ischemic stroke, acute myocardial infarction, intracerebral hemorrhage, fatal extracranial bleeding, and other causes of death. Data were also obtained on the severity and outcome of all recurrent strokes. In addition, researchers gathered individual data on severity of stroke at study entry. The researchers classified recurrent stroke according to the following three time periods: less than six weeks, six to 12 weeks, and more than 12 weeks after randomization.

Aspirin reduced the six-week risk of recurrent ischemic stroke by about 60%. The benefit of aspirin was greatest during the first two weeks, but further benefit accrued up to 12 weeks. Aspirin also decreased the risk of a fatal or disabling stroke by 70% to 80% over the first few days and weeks. Data suggested that administering dipyridamole plus aspirin versus aspirin alone had no impact on the risk or severity of recurrent ischemic stroke within 12 weeks. One fatal extracranial bleed within 12 weeks of randomization was reported. Aspirin did not reduce the severity of recurrent stroke that occurred at 12 or more weeks after TIA.

“Our findings confirm that medical treatment substantially reduces the risk of early recurrent stroke after TIA and minor stroke and identifies aspirin as the key intervention. The considerable early benefit from aspirin warrants public education about self-administration after possible TIA,” the researchers said.

Some limitations of this study include the time period of the trials (the 1980s and 1990s), since medical care has changed since then, and more detailed investigation and intensive lowering of blood pressure and lipids are now possible, the researchers said.

—Erica Robinson

CHICAGO - A study examining the genes of more than 120,000 people from Europe, Asia, Africa and the Americas has offered the clearest picture yet of the genes that drive type 2 diabetes.

The study, published July 11 in the journal Nature, puts to rest a decades-long debate over the genetics that influence the risk of diabetes, which affects one in 10 people over the course of their lifetime.

And it has identified more than a dozen specific genes directly involved in the development of type 2 diabetes that might serve as potential drug targets.

"There was a whole furious debate that arose about this," said Dr. Francis Collins, director of the National Institutes of Health, one of more than 300 scientists collaborating on the work.

Prior studies turned up more than 80 spots in the genome associated with the development of adult-onset diabetes, but most of these genetic errors were common, meaning they occurred frequently in the population, and they explained only a small fraction of disease risk.

These discoveries were based on genome-wide association studies or GWAS, which used gene chips that scan thousands of genes at a time. Researchers used these to scan DNA from large populations of individuals with a specific disease and compare them with DNA from similar groups of healthy people.

Critics, including geneticist Dr. David Goldstein at Columbia University, argued that such studies were a waste of resources because they only found common variants that explained just a small fraction of the risk for disease.

He said the really important drivers of common diseases such as diabetes and schizophrenia were more likely to be found in extremely rare genes, those occurring in individuals or in families, not those shared by large populations of people.

Goldstein "argued very persuasively that it was all about rare variants and we were all going down the wrong road looking at the common ones," Collins said in a telephone interview.

The new study took a deeper look, using next-generation sequencing to search the entire genetic code of 2,657 people with and without diabetes to assess the contribution of both rare and common genes driving diabetes.

They also sequenced all of the protein-making genes in 12,940 people, and used statistical methods to estimate risk in another 111,548 people with less complete DNA data.

They found that, indeed, most of the genetic risk for type 2 diabetes is caused by common mistakes in the genetic code, with each mistake contributing only a small portion of an individual's risk for developing the disease.

"What this study says quite definitively for diabetes is the vast majority of hereditary risk variants are in fact these common ones, and the rare ones, while they pop up here and there, are a much smaller contribution," Collins said.

The study also turned up more than a dozen examples where variants alter the way proteins are made, suggesting that these gene variants have some direct impact on the development of type 2 diabetes.

"These represent promising avenues for efforts to design new ways to treat or prevent the disease," said Mark McCarthy, a senior author of the study from Oxford University.

All of the data will be made publicly available online through the Accelerating Medicines Partnership, a public-private partnership between the NIH, the U.S. Food and Drug Administration, 10 drug companies and several nonprofits.

Goldstein said the work was "a careful, solid investigation" that does not change his view much overall, adding that it was time to "quit arguing."

"What I care about now is finding the exact variants that infer risk, and understanding how they do so," he said.

SOURCE: http://go.nature.com/29DlL5i

Nature 2016.

CHICAGO - A study examining the genes of more than 120,000 people from Europe, Asia, Africa and the Americas has offered the clearest picture yet of the genes that drive type 2 diabetes.

The study, published July 11 in the journal Nature, puts to rest a decades-long debate over the genetics that influence the risk of diabetes, which affects one in 10 people over the course of their lifetime.

And it has identified more than a dozen specific genes directly involved in the development of type 2 diabetes that might serve as potential drug targets.

"There was a whole furious debate that arose about this," said Dr. Francis Collins, director of the National Institutes of Health, one of more than 300 scientists collaborating on the work.

Prior studies turned up more than 80 spots in the genome associated with the development of adult-onset diabetes, but most of these genetic errors were common, meaning they occurred frequently in the population, and they explained only a small fraction of disease risk.

These discoveries were based on genome-wide association studies or GWAS, which used gene chips that scan thousands of genes at a time. Researchers used these to scan DNA from large populations of individuals with a specific disease and compare them with DNA from similar groups of healthy people.

Critics, including geneticist Dr. David Goldstein at Columbia University, argued that such studies were a waste of resources because they only found common variants that explained just a small fraction of the risk for disease.

He said the really important drivers of common diseases such as diabetes and schizophrenia were more likely to be found in extremely rare genes, those occurring in individuals or in families, not those shared by large populations of people.

Goldstein "argued very persuasively that it was all about rare variants and we were all going down the wrong road looking at the common ones," Collins said in a telephone interview.

The new study took a deeper look, using next-generation sequencing to search the entire genetic code of 2,657 people with and without diabetes to assess the contribution of both rare and common genes driving diabetes.

They also sequenced all of the protein-making genes in 12,940 people, and used statistical methods to estimate risk in another 111,548 people with less complete DNA data.

They found that, indeed, most of the genetic risk for type 2 diabetes is caused by common mistakes in the genetic code, with each mistake contributing only a small portion of an individual's risk for developing the disease.

"What this study says quite definitively for diabetes is the vast majority of hereditary risk variants are in fact these common ones, and the rare ones, while they pop up here and there, are a much smaller contribution," Collins said.

The study also turned up more than a dozen examples where variants alter the way proteins are made, suggesting that these gene variants have some direct impact on the development of type 2 diabetes.

"These represent promising avenues for efforts to design new ways to treat or prevent the disease," said Mark McCarthy, a senior author of the study from Oxford University.

All of the data will be made publicly available online through the Accelerating Medicines Partnership, a public-private partnership between the NIH, the U.S. Food and Drug Administration, 10 drug companies and several nonprofits.

Goldstein said the work was "a careful, solid investigation" that does not change his view much overall, adding that it was time to "quit arguing."

"What I care about now is finding the exact variants that infer risk, and understanding how they do so," he said.

SOURCE: http://go.nature.com/29DlL5i

Nature 2016.

CHICAGO - A study examining the genes of more than 120,000 people from Europe, Asia, Africa and the Americas has offered the clearest picture yet of the genes that drive type 2 diabetes.

The study, published July 11 in the journal Nature, puts to rest a decades-long debate over the genetics that influence the risk of diabetes, which affects one in 10 people over the course of their lifetime.

And it has identified more than a dozen specific genes directly involved in the development of type 2 diabetes that might serve as potential drug targets.

"There was a whole furious debate that arose about this," said Dr. Francis Collins, director of the National Institutes of Health, one of more than 300 scientists collaborating on the work.

Prior studies turned up more than 80 spots in the genome associated with the development of adult-onset diabetes, but most of these genetic errors were common, meaning they occurred frequently in the population, and they explained only a small fraction of disease risk.

These discoveries were based on genome-wide association studies or GWAS, which used gene chips that scan thousands of genes at a time. Researchers used these to scan DNA from large populations of individuals with a specific disease and compare them with DNA from similar groups of healthy people.

Critics, including geneticist Dr. David Goldstein at Columbia University, argued that such studies were a waste of resources because they only found common variants that explained just a small fraction of the risk for disease.

He said the really important drivers of common diseases such as diabetes and schizophrenia were more likely to be found in extremely rare genes, those occurring in individuals or in families, not those shared by large populations of people.

Goldstein "argued very persuasively that it was all about rare variants and we were all going down the wrong road looking at the common ones," Collins said in a telephone interview.

The new study took a deeper look, using next-generation sequencing to search the entire genetic code of 2,657 people with and without diabetes to assess the contribution of both rare and common genes driving diabetes.

They also sequenced all of the protein-making genes in 12,940 people, and used statistical methods to estimate risk in another 111,548 people with less complete DNA data.

They found that, indeed, most of the genetic risk for type 2 diabetes is caused by common mistakes in the genetic code, with each mistake contributing only a small portion of an individual's risk for developing the disease.

"What this study says quite definitively for diabetes is the vast majority of hereditary risk variants are in fact these common ones, and the rare ones, while they pop up here and there, are a much smaller contribution," Collins said.

The study also turned up more than a dozen examples where variants alter the way proteins are made, suggesting that these gene variants have some direct impact on the development of type 2 diabetes.

"These represent promising avenues for efforts to design new ways to treat or prevent the disease," said Mark McCarthy, a senior author of the study from Oxford University.

All of the data will be made publicly available online through the Accelerating Medicines Partnership, a public-private partnership between the NIH, the U.S. Food and Drug Administration, 10 drug companies and several nonprofits.

Goldstein said the work was "a careful, solid investigation" that does not change his view much overall, adding that it was time to "quit arguing."

"What I care about now is finding the exact variants that infer risk, and understanding how they do so," he said.

SOURCE: http://go.nature.com/29DlL5i

Nature 2016.

To determine if genetic variation influences the susceptibility to traumatic brain injury and the subsequent posttraumatic seizures, Anne Ritter and her associates from the University of Pittsburgh analyzed the relationship between posttraumatic seizures and single nucleotide polymorphisms (SNPs). Thirty two SNPs were evaluated within SLC1A1 and SLC1A6, which are protein coding genes for glutamate transporters. (Glutamate transporters control glutamate levels and excitatory neurotransmission and have been associated with traumatic brain injury.) The analysis found that among 253 individuals, 49 had experienced posttraumatic seizures. Within this smaller group, they found genotypes at SNP rs10974620 (SLC1A1) linked to the time to the first seizure during a three year follow-up. And after factoring in several confounding variables, rs10974620 remained statistically significant (P = .017).

Rittner AC, Kammerer CM, Brooks MM, Conley YP, Wagner AM. Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure. Epilepsia. 2016;57(6):984-993. 

To determine if genetic variation influences the susceptibility to traumatic brain injury and the subsequent posttraumatic seizures, Anne Ritter and her associates from the University of Pittsburgh analyzed the relationship between posttraumatic seizures and single nucleotide polymorphisms (SNPs). Thirty two SNPs were evaluated within SLC1A1 and SLC1A6, which are protein coding genes for glutamate transporters. (Glutamate transporters control glutamate levels and excitatory neurotransmission and have been associated with traumatic brain injury.) The analysis found that among 253 individuals, 49 had experienced posttraumatic seizures. Within this smaller group, they found genotypes at SNP rs10974620 (SLC1A1) linked to the time to the first seizure during a three year follow-up. And after factoring in several confounding variables, rs10974620 remained statistically significant (P = .017).

Rittner AC, Kammerer CM, Brooks MM, Conley YP, Wagner AM. Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure. Epilepsia. 2016;57(6):984-993. 

To determine if genetic variation influences the susceptibility to traumatic brain injury and the subsequent posttraumatic seizures, Anne Ritter and her associates from the University of Pittsburgh analyzed the relationship between posttraumatic seizures and single nucleotide polymorphisms (SNPs). Thirty two SNPs were evaluated within SLC1A1 and SLC1A6, which are protein coding genes for glutamate transporters. (Glutamate transporters control glutamate levels and excitatory neurotransmission and have been associated with traumatic brain injury.) The analysis found that among 253 individuals, 49 had experienced posttraumatic seizures. Within this smaller group, they found genotypes at SNP rs10974620 (SLC1A1) linked to the time to the first seizure during a three year follow-up. And after factoring in several confounding variables, rs10974620 remained statistically significant (P = .017).

Rittner AC, Kammerer CM, Brooks MM, Conley YP, Wagner AM. Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure. Epilepsia. 2016;57(6):984-993. 

To determine the unique characteristics of cluster seizures, investigators looked at 92 subjects, 83% of whom had at least one seizure cluster. They found that seizures occurring within a cluster were significantly shorter than the last seizure that occurred in the cluster. They also discovered that the terminal seizure in a cluster is similar to duration in isolated seizures that are not part of a cluster. Finally, the researchers found that cluster seizures are more likely to occur in the frontal and temporal lobes.

Ferastraoaru V, Schulze-Bonhage A, Lipton RB, Dumpelmann M, Legatt AD, Hunt SR. Termination of seizure clusters is related to duration of focal seizures. Epilepsia. 2016;57(6):889-895.

To determine the unique characteristics of cluster seizures, investigators looked at 92 subjects, 83% of whom had at least one seizure cluster. They found that seizures occurring within a cluster were significantly shorter than the last seizure that occurred in the cluster. They also discovered that the terminal seizure in a cluster is similar to duration in isolated seizures that are not part of a cluster. Finally, the researchers found that cluster seizures are more likely to occur in the frontal and temporal lobes.

Ferastraoaru V, Schulze-Bonhage A, Lipton RB, Dumpelmann M, Legatt AD, Hunt SR. Termination of seizure clusters is related to duration of focal seizures. Epilepsia. 2016;57(6):889-895.

To determine the unique characteristics of cluster seizures, investigators looked at 92 subjects, 83% of whom had at least one seizure cluster. They found that seizures occurring within a cluster were significantly shorter than the last seizure that occurred in the cluster. They also discovered that the terminal seizure in a cluster is similar to duration in isolated seizures that are not part of a cluster. Finally, the researchers found that cluster seizures are more likely to occur in the frontal and temporal lobes.

Ferastraoaru V, Schulze-Bonhage A, Lipton RB, Dumpelmann M, Legatt AD, Hunt SR. Termination of seizure clusters is related to duration of focal seizures. Epilepsia. 2016;57(6):889-895.

To determine the unique characteristics of cluster seizures, investigators looked at 92 subjects, 83% of whom had at least one seizure cluster. They found that seizures occurring within a cluster were significantly shorter than the last seizure that occurred in the cluster. They also discovered that the terminal seizure in a cluster is similar to duration in isolated seizures that are not part of a cluster. Finally, the researchers found that cluster seizures are more likely to occur in the frontal and temporal lobes.

Ferastraoaru V, Schulze-Bonhage A, Lipton RB, Dumpelmann M, Legatt AD, Hunt SR. Termination of seizure clusters is related to duration of focal seizures. Epilepsia. 2016;57(6):889-895.

To determine the unique characteristics of cluster seizures, investigators looked at 92 subjects, 83% of whom had at least one seizure cluster. They found that seizures occurring within a cluster were significantly shorter than the last seizure that occurred in the cluster. They also discovered that the terminal seizure in a cluster is similar to duration in isolated seizures that are not part of a cluster. Finally, the researchers found that cluster seizures are more likely to occur in the frontal and temporal lobes.

Ferastraoaru V, Schulze-Bonhage A, Lipton RB, Dumpelmann M, Legatt AD, Hunt SR. Termination of seizure clusters is related to duration of focal seizures. Epilepsia. 2016;57(6):889-895.

To determine the unique characteristics of cluster seizures, investigators looked at 92 subjects, 83% of whom had at least one seizure cluster. They found that seizures occurring within a cluster were significantly shorter than the last seizure that occurred in the cluster. They also discovered that the terminal seizure in a cluster is similar to duration in isolated seizures that are not part of a cluster. Finally, the researchers found that cluster seizures are more likely to occur in the frontal and temporal lobes.

Ferastraoaru V, Schulze-Bonhage A, Lipton RB, Dumpelmann M, Legatt AD, Hunt SR. Termination of seizure clusters is related to duration of focal seizures. Epilepsia. 2016;57(6):889-895.

To determine if genetic variation influences the susceptibility to traumatic brain injury and the subsequent posttraumatic seizures, Anne Ritter and her associates from the University of Pittsburgh analyzed the relationship between posttraumatic seizures and single nucleotide polymorphisms (SNPs). Thirty two SNPs were evaluated within SLC1A1 and SLC1A6, which are protein coding genes for glutamate transporters. (Glutamate transporters control glutamate levels and excitatory neurotransmission and have been associated with traumatic brain injury.) The analysis found that among 253 individuals, 49 had experienced posttraumatic seizures. Within this smaller group, they found genotypes at SNP rs10974620 (SLC1A1) linked to the time to the first seizure during a three year follow-up. And after factoring in several confounding variables, rs10974620 remained statistically significant (P = .017).

Rittner AC, Kammerer CM, Brooks MM, Conley YP, Wagner AM. Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure. Epilepsia. 2016;57(6):984-993. 

To determine if genetic variation influences the susceptibility to traumatic brain injury and the subsequent posttraumatic seizures, Anne Ritter and her associates from the University of Pittsburgh analyzed the relationship between posttraumatic seizures and single nucleotide polymorphisms (SNPs). Thirty two SNPs were evaluated within SLC1A1 and SLC1A6, which are protein coding genes for glutamate transporters. (Glutamate transporters control glutamate levels and excitatory neurotransmission and have been associated with traumatic brain injury.) The analysis found that among 253 individuals, 49 had experienced posttraumatic seizures. Within this smaller group, they found genotypes at SNP rs10974620 (SLC1A1) linked to the time to the first seizure during a three year follow-up. And after factoring in several confounding variables, rs10974620 remained statistically significant (P = .017).

Rittner AC, Kammerer CM, Brooks MM, Conley YP, Wagner AM. Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure. Epilepsia. 2016;57(6):984-993. 

To determine if genetic variation influences the susceptibility to traumatic brain injury and the subsequent posttraumatic seizures, Anne Ritter and her associates from the University of Pittsburgh analyzed the relationship between posttraumatic seizures and single nucleotide polymorphisms (SNPs). Thirty two SNPs were evaluated within SLC1A1 and SLC1A6, which are protein coding genes for glutamate transporters. (Glutamate transporters control glutamate levels and excitatory neurotransmission and have been associated with traumatic brain injury.) The analysis found that among 253 individuals, 49 had experienced posttraumatic seizures. Within this smaller group, they found genotypes at SNP rs10974620 (SLC1A1) linked to the time to the first seizure during a three year follow-up. And after factoring in several confounding variables, rs10974620 remained statistically significant (P = .017).

Rittner AC, Kammerer CM, Brooks MM, Conley YP, Wagner AM. Genetic variation in neuronal glutamate transport genes and associations with posttraumatic seizure. Epilepsia. 2016;57(6):984-993. 

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: Which medications are most safe and effective at managing type 2 diabetes?

Background: Patients and practitioners need an updated review of the evidence to select the optimal medication for type 2 diabetes management.

Study design: Systematic review.

Synopsis: The authors reviewed 179 trials and 25 observational studies. When comparing metformin to sulfonylureas, metformin was associated with less cardiovascular mortality.

However, when trying to make comparisons based on all-cause mortality or microvascular complications, the evidence is limited. Improvements in hemoglobin A1c levels are similar when comparing different monotherapy options, and low blood sugar was most common with sulfonylureas. The short duration of many trials limits the ability to provide better data on long-term outcomes.

Bottom line: Metformin remains the first-line agent for type 2 diabetes management.

Citation: Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systemic review and meta-analysis. Ann Intern Med. 2016;164(1):740-751.

Short Take

Patients Discharge Readiness May Not Be Adequately Assessed and/or Addressed During Hospitalization

Prospective observational study found unresolved barriers to discharge were common in at least 90% of patients. Patients frequently cited issues including unresolved pain, lack of understanding around discharge plans, and ability to provide self-care.

Citation: Harrison JD, Greysen RS, Jacolbia R, Nguyen A, Auerbach AD. Not ready, not set…discharge: patient-reported barriers to discharge readiness at an academic medical center [published online ahead of print April 15, 2016]. J Hosp Med. doi:10.1002/jhm.2591.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

Clinical question: What is the prognosis of patients who have a TIA or minor stroke?

Background: Prior studies had estimated the risk in the three months following a TIA or minor stroke of having a stroke or acute coronary syndrome (ACS) as 12% to 20%, but this may not reflect the risk of modern patients receiving the current standards of care.

Study design: Prospective observational registry of patients with recent TIA or minor stroke.

Setting: International, including 21 countries.

Synopsis: Adults with recent TIA or minor stroke were included in this multi-center, international registry, and one-year outcomes were reported. At one year, the Kaplan-Meier estimated event rate for the combined outcome of stroke, ACS, or death from cardiovascular causes was 6.2%. The risk of the cardiovascular events was found to be lower than previously reported, suggesting an improvement in outcomes with current interventions. Elevated ABCD2 score, infarction seen on brain imaging, and large-artery atherosclerosis were each associated with higher risk.

Bottom line: Elevated ABCD2 score, brain imaging findings, and large-artery atherosclerosis suggest increased risk for recurrent stroke.

Citation: Amarenco P, Lavallée PC, Labreuche J, et al. One-year risk of stroke after transient ischemic attack or minor stroke. N Engl J Med. 2016;374(16):1533-1542.

The American Heart Association/American Stroke Association has issued its first guideline on adult stroke rehabilitation. Published in the June issue of Stroke, the guideline calls for intensive, multidisciplinary treatment in an inpatient rehabilitation facility.

“Previous guidelines have focused on the medical issues involved in the initial management of stroke, but many people survive a stroke with some level of disability. There is increasing evidence that rehabilitation can have a big impact on the survivors’ quality of life, so the time is right to review the evidence in this complex field and highlight effective and important aspects of rehabilitation,” said Carolee J. Winstein, PhD, PT, lead author of the guideline and Professor of Biokinesiology and Physical Therapy at the University of Southern California in Los Angeles.

Carolee J. Winstein, PhD, PT

The American Stroke Association strongly recommends that stroke patients be treated at an inpatient rehabilitation facility whenever possible, rather than at a skilled nursing facility. While in an inpatient rehabilitation facility, a patient participates in at least three hours of rehabilitation per day with physical therapists, occupational therapists, and speech therapists. Nurses are continuously available, and doctors typically visit daily.

“There is considerable evidence that patients benefit from the team approach in a facility that understands the importance of rehabilitation during the early period after a stroke,” said Dr. Winstein.

According to Dr. Winstein and her coauthors, caregivers should advocate for discharge to an inpatient rehabilitation facility and insist that a stroke survivor not be discharged from the hospital until he or she has participated in a structured program on preventing falls. This program should include education about changes to make the home safer (eg, removing throw rugs and improving lighting), minimizing the fall risk resulting from the side effects of medication, and safely using assistive devices such as wheelchairs, walkers, and canes.

“This recommendation will probably change medical practice. Even the top stroke centers may not have a formal falls-prevention program, but it is very important because a high percentage of patients end up falling after a stroke,” Dr. Winstein said.

The guideline also recommends the following measures:

• Intense mobility-task training after stroke for all survivors with walking limitations to relearn activities such as climbing stairs

• An individually tailored exercise program that allows survivors to safely continue to improve their cardiovascular fitness through proper exercise and physical activity after formal rehabilitation is complete

• An enriched environment (which might include a computer, books, music, and games) to increase engagement and cognitive activities during rehabilitation

• Speech therapy for those with difficulty speaking following a stroke

• Eye exercises for survivors with difficulty focusing on near objects

• A balance training program for survivors with poor balance, or who are at risk for falls.

“For a person to fulfill his or her full potential after stroke, there needs to be a coordinated effort and ongoing communication between a team of professionals, as well as the patient, family, and caregivers,” Dr. Winstein said.

The American Heart Association/American Stroke Association has issued its first guideline on adult stroke rehabilitation. Published in the June issue of Stroke, the guideline calls for intensive, multidisciplinary treatment in an inpatient rehabilitation facility.

“Previous guidelines have focused on the medical issues involved in the initial management of stroke, but many people survive a stroke with some level of disability. There is increasing evidence that rehabilitation can have a big impact on the survivors’ quality of life, so the time is right to review the evidence in this complex field and highlight effective and important aspects of rehabilitation,” said Carolee J. Winstein, PhD, PT, lead author of the guideline and Professor of Biokinesiology and Physical Therapy at the University of Southern California in Los Angeles.

Carolee J. Winstein, PhD, PT

The American Stroke Association strongly recommends that stroke patients be treated at an inpatient rehabilitation facility whenever possible, rather than at a skilled nursing facility. While in an inpatient rehabilitation facility, a patient participates in at least three hours of rehabilitation per day with physical therapists, occupational therapists, and speech therapists. Nurses are continuously available, and doctors typically visit daily.

“There is considerable evidence that patients benefit from the team approach in a facility that understands the importance of rehabilitation during the early period after a stroke,” said Dr. Winstein.

According to Dr. Winstein and her coauthors, caregivers should advocate for discharge to an inpatient rehabilitation facility and insist that a stroke survivor not be discharged from the hospital until he or she has participated in a structured program on preventing falls. This program should include education about changes to make the home safer (eg, removing throw rugs and improving lighting), minimizing the fall risk resulting from the side effects of medication, and safely using assistive devices such as wheelchairs, walkers, and canes.

“This recommendation will probably change medical practice. Even the top stroke centers may not have a formal falls-prevention program, but it is very important because a high percentage of patients end up falling after a stroke,” Dr. Winstein said.

The guideline also recommends the following measures:

• Intense mobility-task training after stroke for all survivors with walking limitations to relearn activities such as climbing stairs

• An individually tailored exercise program that allows survivors to safely continue to improve their cardiovascular fitness through proper exercise and physical activity after formal rehabilitation is complete

• An enriched environment (which might include a computer, books, music, and games) to increase engagement and cognitive activities during rehabilitation

• Speech therapy for those with difficulty speaking following a stroke

• Eye exercises for survivors with difficulty focusing on near objects

• A balance training program for survivors with poor balance, or who are at risk for falls.

“For a person to fulfill his or her full potential after stroke, there needs to be a coordinated effort and ongoing communication between a team of professionals, as well as the patient, family, and caregivers,” Dr. Winstein said.

The American Heart Association/American Stroke Association has issued its first guideline on adult stroke rehabilitation. Published in the June issue of Stroke, the guideline calls for intensive, multidisciplinary treatment in an inpatient rehabilitation facility.

“Previous guidelines have focused on the medical issues involved in the initial management of stroke, but many people survive a stroke with some level of disability. There is increasing evidence that rehabilitation can have a big impact on the survivors’ quality of life, so the time is right to review the evidence in this complex field and highlight effective and important aspects of rehabilitation,” said Carolee J. Winstein, PhD, PT, lead author of the guideline and Professor of Biokinesiology and Physical Therapy at the University of Southern California in Los Angeles.

Carolee J. Winstein, PhD, PT

The American Stroke Association strongly recommends that stroke patients be treated at an inpatient rehabilitation facility whenever possible, rather than at a skilled nursing facility. While in an inpatient rehabilitation facility, a patient participates in at least three hours of rehabilitation per day with physical therapists, occupational therapists, and speech therapists. Nurses are continuously available, and doctors typically visit daily.

“There is considerable evidence that patients benefit from the team approach in a facility that understands the importance of rehabilitation during the early period after a stroke,” said Dr. Winstein.

According to Dr. Winstein and her coauthors, caregivers should advocate for discharge to an inpatient rehabilitation facility and insist that a stroke survivor not be discharged from the hospital until he or she has participated in a structured program on preventing falls. This program should include education about changes to make the home safer (eg, removing throw rugs and improving lighting), minimizing the fall risk resulting from the side effects of medication, and safely using assistive devices such as wheelchairs, walkers, and canes.

“This recommendation will probably change medical practice. Even the top stroke centers may not have a formal falls-prevention program, but it is very important because a high percentage of patients end up falling after a stroke,” Dr. Winstein said.

The guideline also recommends the following measures:

• Intense mobility-task training after stroke for all survivors with walking limitations to relearn activities such as climbing stairs

• An individually tailored exercise program that allows survivors to safely continue to improve their cardiovascular fitness through proper exercise and physical activity after formal rehabilitation is complete

• An enriched environment (which might include a computer, books, music, and games) to increase engagement and cognitive activities during rehabilitation

• Speech therapy for those with difficulty speaking following a stroke

• Eye exercises for survivors with difficulty focusing on near objects

• A balance training program for survivors with poor balance, or who are at risk for falls.

“For a person to fulfill his or her full potential after stroke, there needs to be a coordinated effort and ongoing communication between a team of professionals, as well as the patient, family, and caregivers,” Dr. Winstein said.