MDedge Neurology

LOS ANGELES – Prevention of shingles with the Zoster Vaccine Live may reduce the risk of subsequent stroke among older adults as well, the first study to examine this association suggests. Shingles vaccination was linked to a 20% decrease in stroke risk in people younger than 80 years of age in the large Medicare cohort study. Older participants showed a 10% reduced risk, according to data released in advance of formal presentation at this week’s International Stroke Conference, sponsored by the American Heart Association.

Reductions were seen for both ischemic and hemorrhagic events.

“Our findings might encourage people age 50 or older to get vaccinated against shingles and to prevent shingles-associated stroke risk,” Quanhe Yang, PhD, lead study author and senior scientist at the Centers for Disease Control and Prevention, said in an interview.

Dr. Yang and colleagues evaluated the only shingles vaccine available at the time of the study, Zoster Vaccine Live (Zostavax). However, the CDC now calls an adjuvanted, nonlive recombinant vaccine (Shingrix) the preferred shingles vaccine for healthy adults aged 50 years and older. Shingrix was approved in 2017. Zostavax, approved in 2006, can still be used in healthy adults aged 60 years and older, the agency states.

A reduction in inflammation from Zoster Vaccine Live may be the mechanism by which stroke risk is reduced, Dr. Yang said. The newer vaccine, which the CDC notes is more than 90% effective, might provide even greater protection against stroke, although more research is needed, he added.

Interestingly, prior research suggested that, once a person develops shingles, it may be too late. Dr. Yang and colleagues showed vaccination or antiviral treatment after a shingles episode was not effective at reducing stroke risk in research presented at the 2019 International Stroke Conference.

Shingles can present as a painful reactivation of chickenpox, also known as the varicella-zoster virus. Shingles is also common; Dr. Yang estimated one in three people who had chickenpox will develop the condition at some point in their lifetime. In addition, researchers have linked shingles to an elevated risk of stroke.

To assess the vaccine’s protective effect on stroke, Dr. Yang and colleagues reviewed health records for 1.38 million Medicare recipients. All participants were aged 66 years or older, had no history of stroke at baseline, and received the Zoster Vaccine Live during 2008-2016. The investigators compared the stroke rate in this vaccinated group with the rate in a matched control group of the same number of Medicare fee-for-service beneficiaries who did not receive the vaccination. They adjusted their analysis for age, sex, race, medications, and comorbidities.

The overall decrease of 16% in stroke risk associated with vaccination included a 12% drop in hemorrhagic stroke and 18% decrease in ischemic stroke over a median follow-up of 3.9 years follow-up (interquartile range, 2.7-5.4).

The adjusted hazard ratios comparing the vaccinated with control groups were 0.84 (95% confidence interval, 0.83-0.85) for all stroke; 0.82 (95% CI, 0.81-0.83) for acute ischemic stroke; and 0.88 (95% CI, 0.84-0.91) for hemorrhagic stroke.

The vaccinated group experienced 42,267 stroke events during that time. This rate included 33,510 acute ischemic strokes and 4,318 hemorrhagic strokes. At the same time, 48,139 strokes occurred in the control group. The breakdown included 39,334 ischemic and 4,713 hemorrhagic events.

“Approximately 1 million people in the United States get shingles each year, yet there is a vaccine to help prevent it,” Dr. Yang stated in a news release. “Our study results may encourage people ages 50 and older to follow the recommendation and get vaccinated against shingles. You are reducing the risk of shingles, and at the same time, you may be reducing your risk of stroke.”

“Further studies are needed to confirm our findings of association between Zostavax vaccine and risk of stroke,” Dr. Yang said.

Because the CDC Advisory Committee on Immunization Practices recommended Shingrix vaccine only for healthy adults 50 years and older in 2017, there were insufficient data in Medicare to study the association between that vaccine and risk of stroke at the time of the current study.

“However, two doses of Shingrix are more than 90% effective at preventing shingles and postherpetic neuralgia, and higher than that of Zostavax,” Dr. Yang said.

‘Very intriguing’ research

“This is a very interesting study,” Ralph L. Sacco, MD, past president of the American Heart Association, said in a video commentary released in advance of the conference. It was a very large sample, he noted, and those older than age 60 years who had the vaccine were protected with a lower risk for both ischemic and hemorrhagic stroke.

“So it is very intriguing,” added Dr. Sacco, chairman of the department of neurology at the University of Miami. “We know things like shingles can increase inflammation and increase the risk of stroke,” Dr. Sacco said, “but this is the first time in a very large Medicare database that it was shown that those who had the vaccine had a lower risk of stroke.”

The CDC funded this study. Dr. Yang and Dr. Sacco have disclosed no relevant financial relationships.

SOURCE: Yang Q et al. ISC 2020, Abstract TP493.

This article first appeared on Medscape.com.

LOS ANGELES – Prevention of shingles with the Zoster Vaccine Live may reduce the risk of subsequent stroke among older adults as well, the first study to examine this association suggests. Shingles vaccination was linked to a 20% decrease in stroke risk in people younger than 80 years of age in the large Medicare cohort study. Older participants showed a 10% reduced risk, according to data released in advance of formal presentation at this week’s International Stroke Conference, sponsored by the American Heart Association.

Reductions were seen for both ischemic and hemorrhagic events.

“Our findings might encourage people age 50 or older to get vaccinated against shingles and to prevent shingles-associated stroke risk,” Quanhe Yang, PhD, lead study author and senior scientist at the Centers for Disease Control and Prevention, said in an interview.

Dr. Yang and colleagues evaluated the only shingles vaccine available at the time of the study, Zoster Vaccine Live (Zostavax). However, the CDC now calls an adjuvanted, nonlive recombinant vaccine (Shingrix) the preferred shingles vaccine for healthy adults aged 50 years and older. Shingrix was approved in 2017. Zostavax, approved in 2006, can still be used in healthy adults aged 60 years and older, the agency states.

A reduction in inflammation from Zoster Vaccine Live may be the mechanism by which stroke risk is reduced, Dr. Yang said. The newer vaccine, which the CDC notes is more than 90% effective, might provide even greater protection against stroke, although more research is needed, he added.

Interestingly, prior research suggested that, once a person develops shingles, it may be too late. Dr. Yang and colleagues showed vaccination or antiviral treatment after a shingles episode was not effective at reducing stroke risk in research presented at the 2019 International Stroke Conference.

Shingles can present as a painful reactivation of chickenpox, also known as the varicella-zoster virus. Shingles is also common; Dr. Yang estimated one in three people who had chickenpox will develop the condition at some point in their lifetime. In addition, researchers have linked shingles to an elevated risk of stroke.

To assess the vaccine’s protective effect on stroke, Dr. Yang and colleagues reviewed health records for 1.38 million Medicare recipients. All participants were aged 66 years or older, had no history of stroke at baseline, and received the Zoster Vaccine Live during 2008-2016. The investigators compared the stroke rate in this vaccinated group with the rate in a matched control group of the same number of Medicare fee-for-service beneficiaries who did not receive the vaccination. They adjusted their analysis for age, sex, race, medications, and comorbidities.

The overall decrease of 16% in stroke risk associated with vaccination included a 12% drop in hemorrhagic stroke and 18% decrease in ischemic stroke over a median follow-up of 3.9 years follow-up (interquartile range, 2.7-5.4).

The adjusted hazard ratios comparing the vaccinated with control groups were 0.84 (95% confidence interval, 0.83-0.85) for all stroke; 0.82 (95% CI, 0.81-0.83) for acute ischemic stroke; and 0.88 (95% CI, 0.84-0.91) for hemorrhagic stroke.

The vaccinated group experienced 42,267 stroke events during that time. This rate included 33,510 acute ischemic strokes and 4,318 hemorrhagic strokes. At the same time, 48,139 strokes occurred in the control group. The breakdown included 39,334 ischemic and 4,713 hemorrhagic events.

“Approximately 1 million people in the United States get shingles each year, yet there is a vaccine to help prevent it,” Dr. Yang stated in a news release. “Our study results may encourage people ages 50 and older to follow the recommendation and get vaccinated against shingles. You are reducing the risk of shingles, and at the same time, you may be reducing your risk of stroke.”

“Further studies are needed to confirm our findings of association between Zostavax vaccine and risk of stroke,” Dr. Yang said.

Because the CDC Advisory Committee on Immunization Practices recommended Shingrix vaccine only for healthy adults 50 years and older in 2017, there were insufficient data in Medicare to study the association between that vaccine and risk of stroke at the time of the current study.

“However, two doses of Shingrix are more than 90% effective at preventing shingles and postherpetic neuralgia, and higher than that of Zostavax,” Dr. Yang said.

‘Very intriguing’ research

“This is a very interesting study,” Ralph L. Sacco, MD, past president of the American Heart Association, said in a video commentary released in advance of the conference. It was a very large sample, he noted, and those older than age 60 years who had the vaccine were protected with a lower risk for both ischemic and hemorrhagic stroke.

“So it is very intriguing,” added Dr. Sacco, chairman of the department of neurology at the University of Miami. “We know things like shingles can increase inflammation and increase the risk of stroke,” Dr. Sacco said, “but this is the first time in a very large Medicare database that it was shown that those who had the vaccine had a lower risk of stroke.”

The CDC funded this study. Dr. Yang and Dr. Sacco have disclosed no relevant financial relationships.

SOURCE: Yang Q et al. ISC 2020, Abstract TP493.

This article first appeared on Medscape.com.

LOS ANGELES – Prevention of shingles with the Zoster Vaccine Live may reduce the risk of subsequent stroke among older adults as well, the first study to examine this association suggests. Shingles vaccination was linked to a 20% decrease in stroke risk in people younger than 80 years of age in the large Medicare cohort study. Older participants showed a 10% reduced risk, according to data released in advance of formal presentation at this week’s International Stroke Conference, sponsored by the American Heart Association.

Reductions were seen for both ischemic and hemorrhagic events.

“Our findings might encourage people age 50 or older to get vaccinated against shingles and to prevent shingles-associated stroke risk,” Quanhe Yang, PhD, lead study author and senior scientist at the Centers for Disease Control and Prevention, said in an interview.

Dr. Yang and colleagues evaluated the only shingles vaccine available at the time of the study, Zoster Vaccine Live (Zostavax). However, the CDC now calls an adjuvanted, nonlive recombinant vaccine (Shingrix) the preferred shingles vaccine for healthy adults aged 50 years and older. Shingrix was approved in 2017. Zostavax, approved in 2006, can still be used in healthy adults aged 60 years and older, the agency states.

A reduction in inflammation from Zoster Vaccine Live may be the mechanism by which stroke risk is reduced, Dr. Yang said. The newer vaccine, which the CDC notes is more than 90% effective, might provide even greater protection against stroke, although more research is needed, he added.

Interestingly, prior research suggested that, once a person develops shingles, it may be too late. Dr. Yang and colleagues showed vaccination or antiviral treatment after a shingles episode was not effective at reducing stroke risk in research presented at the 2019 International Stroke Conference.

Shingles can present as a painful reactivation of chickenpox, also known as the varicella-zoster virus. Shingles is also common; Dr. Yang estimated one in three people who had chickenpox will develop the condition at some point in their lifetime. In addition, researchers have linked shingles to an elevated risk of stroke.

To assess the vaccine’s protective effect on stroke, Dr. Yang and colleagues reviewed health records for 1.38 million Medicare recipients. All participants were aged 66 years or older, had no history of stroke at baseline, and received the Zoster Vaccine Live during 2008-2016. The investigators compared the stroke rate in this vaccinated group with the rate in a matched control group of the same number of Medicare fee-for-service beneficiaries who did not receive the vaccination. They adjusted their analysis for age, sex, race, medications, and comorbidities.

The overall decrease of 16% in stroke risk associated with vaccination included a 12% drop in hemorrhagic stroke and 18% decrease in ischemic stroke over a median follow-up of 3.9 years follow-up (interquartile range, 2.7-5.4).

The adjusted hazard ratios comparing the vaccinated with control groups were 0.84 (95% confidence interval, 0.83-0.85) for all stroke; 0.82 (95% CI, 0.81-0.83) for acute ischemic stroke; and 0.88 (95% CI, 0.84-0.91) for hemorrhagic stroke.

The vaccinated group experienced 42,267 stroke events during that time. This rate included 33,510 acute ischemic strokes and 4,318 hemorrhagic strokes. At the same time, 48,139 strokes occurred in the control group. The breakdown included 39,334 ischemic and 4,713 hemorrhagic events.

“Approximately 1 million people in the United States get shingles each year, yet there is a vaccine to help prevent it,” Dr. Yang stated in a news release. “Our study results may encourage people ages 50 and older to follow the recommendation and get vaccinated against shingles. You are reducing the risk of shingles, and at the same time, you may be reducing your risk of stroke.”

“Further studies are needed to confirm our findings of association between Zostavax vaccine and risk of stroke,” Dr. Yang said.

Because the CDC Advisory Committee on Immunization Practices recommended Shingrix vaccine only for healthy adults 50 years and older in 2017, there were insufficient data in Medicare to study the association between that vaccine and risk of stroke at the time of the current study.

“However, two doses of Shingrix are more than 90% effective at preventing shingles and postherpetic neuralgia, and higher than that of Zostavax,” Dr. Yang said.

‘Very intriguing’ research

“This is a very interesting study,” Ralph L. Sacco, MD, past president of the American Heart Association, said in a video commentary released in advance of the conference. It was a very large sample, he noted, and those older than age 60 years who had the vaccine were protected with a lower risk for both ischemic and hemorrhagic stroke.

“So it is very intriguing,” added Dr. Sacco, chairman of the department of neurology at the University of Miami. “We know things like shingles can increase inflammation and increase the risk of stroke,” Dr. Sacco said, “but this is the first time in a very large Medicare database that it was shown that those who had the vaccine had a lower risk of stroke.”

The CDC funded this study. Dr. Yang and Dr. Sacco have disclosed no relevant financial relationships.

SOURCE: Yang Q et al. ISC 2020, Abstract TP493.

This article first appeared on Medscape.com.

LOS ANGELES – Evidence continues to mount that diabetic retinopathy predicts elevated risk for stroke.

In a new study with nearly 3,000 people, those with diabetic retinopathy were 60% more likely than others with diabetes to develop an incident stroke over time. Investigators also found that addressing glucose, lipids, and blood pressure levels did not mitigate this risk in this secondary analysis of the ACCORD Eye Study.

“We are not surprised with the finding that diabetic retinopathy increases the risk of stroke — as diabetic retinopathy is common microvascular disease that is an established risk factor for cardiovascular disease,” lead author Ka-Ho Wong, BS, MBA, said in an interview.

However, “we were surprised that none of the trial interventions mitigated this risk, in particular the intensive blood pressure reduction, because hypertension is the most important cause of microvascular disease,” he said. Mr. Wong is clinical research coordinator and lab manager of the de Havenon Lab at the University of Utah Health Hospitals and Clinics in Salt Lake City.

The study findings were released Feb. 12, 2020, in advance of formal presentation at the International Stroke Conference sponsored by the American Heart Association.
 

Common predictor of vascular disease

Diabetic retinopathy is the most common complication of diabetes mellitus, affecting up to 50% of people living with type 1 and type 2 diabetes. In addition, previous research suggests that macrovascular diabetes complications, including stroke, could share a common or synergistic pathway.

This small vessel damage in the eye also has been linked to an increased risk of adverse cardiac events, including heart failure, as previously reported by Medscape Medical News.

To find out more, Mr. Wong and colleagues analyzed 2,828 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. They compared the stroke risk between 874 people with diabetic retinopathy and another 1,954 diabetics without this complication. The average age was 62 years and 62% were men.

Diabetic neuropathy at baseline was diagnosed using the Early Treatment Diabetic Retinopathy Study Severity Scale using seven-field stereoscopic fundus photographs.

A total of 117 participants experienced a stroke during a mean follow-up of 5.4 years.

The investigators found that diabetic retinopathy was more common among patients who had a stroke (41%) versus 31% of those without a stroke (P = .016). The link between diabetic retinopathy and stroke remained in an analysis adjusted for multiple factors, including baseline age, gender, race, total cholesterol, A_1c, smoking, and more. Risk remained elevated, with a hazard ratio of 1.60 (95% confidence interval, 1.10-2.32; P = .015).

Regarding the potential for modifying this risk, the association was unaffected among participants randomly assigned to the ACCORD glucose intervention (P = .305), lipid intervention (P = .546), or blood pressure intervention (P = .422).

The study was a secondary analysis, so information on stroke type and location were unavailable.
 

The big picture

“Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications,” the researchers noted.

Despite these findings, the researchers suggest that patients with diabetic retinopathy receive aggressive medical management to try to reduce their stroke risk.

“It’s important for everyone with diabetes to maintain good blood glucose control, and those with established diabetic retinopathy should pay particular attention to meeting all the stroke prevention guidelines that are established by the American Stroke Association,” said Mr. Wong.

“Patients with established diabetic retinopathy should pay particular attention to meeting all stroke prevention guidelines established by the [American Heart Association],” he added.

Mr. Wong and colleagues would like to expand on these findings. Pending grant application and funding support, they propose conducting a prospective, observational trial in stroke patients with baseline diabetic retinopathy. One aim would be to identify the most common mechanisms leading to stroke in this population, “which would have important implications for prevention efforts,” he said.
 

Consistent Findings

“The results of the study showing that having diabetic retinopathy is also associated with an increase in stroke really isn’t surprising. There have been other studies, population-based studies, done in the past, that have found a similar relationship,” Larry B. Goldstein, MD, said in a video commentary on the findings.

“The results are actually quite consistent with several other studies that have evaluated the same relationship,” added Dr. Goldstein, who is chair of the department of neurology and codirector of the Kentucky Neuroscience Institute, University of Kentucky HealthCare, Lexington.

Mr. Wong and Dr. Goldstein have disclosed no relevant financial relationships. The NIH’s National Institute of Neurological Disorders and Stroke funded the study.

This article first appeared on Medscape.com.

LOS ANGELES – Evidence continues to mount that diabetic retinopathy predicts elevated risk for stroke.

In a new study with nearly 3,000 people, those with diabetic retinopathy were 60% more likely than others with diabetes to develop an incident stroke over time. Investigators also found that addressing glucose, lipids, and blood pressure levels did not mitigate this risk in this secondary analysis of the ACCORD Eye Study.

“We are not surprised with the finding that diabetic retinopathy increases the risk of stroke — as diabetic retinopathy is common microvascular disease that is an established risk factor for cardiovascular disease,” lead author Ka-Ho Wong, BS, MBA, said in an interview.

However, “we were surprised that none of the trial interventions mitigated this risk, in particular the intensive blood pressure reduction, because hypertension is the most important cause of microvascular disease,” he said. Mr. Wong is clinical research coordinator and lab manager of the de Havenon Lab at the University of Utah Health Hospitals and Clinics in Salt Lake City.

The study findings were released Feb. 12, 2020, in advance of formal presentation at the International Stroke Conference sponsored by the American Heart Association.
 

Common predictor of vascular disease

Diabetic retinopathy is the most common complication of diabetes mellitus, affecting up to 50% of people living with type 1 and type 2 diabetes. In addition, previous research suggests that macrovascular diabetes complications, including stroke, could share a common or synergistic pathway.

This small vessel damage in the eye also has been linked to an increased risk of adverse cardiac events, including heart failure, as previously reported by Medscape Medical News.

To find out more, Mr. Wong and colleagues analyzed 2,828 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. They compared the stroke risk between 874 people with diabetic retinopathy and another 1,954 diabetics without this complication. The average age was 62 years and 62% were men.

Diabetic neuropathy at baseline was diagnosed using the Early Treatment Diabetic Retinopathy Study Severity Scale using seven-field stereoscopic fundus photographs.

A total of 117 participants experienced a stroke during a mean follow-up of 5.4 years.

The investigators found that diabetic retinopathy was more common among patients who had a stroke (41%) versus 31% of those without a stroke (P = .016). The link between diabetic retinopathy and stroke remained in an analysis adjusted for multiple factors, including baseline age, gender, race, total cholesterol, A_1c, smoking, and more. Risk remained elevated, with a hazard ratio of 1.60 (95% confidence interval, 1.10-2.32; P = .015).

Regarding the potential for modifying this risk, the association was unaffected among participants randomly assigned to the ACCORD glucose intervention (P = .305), lipid intervention (P = .546), or blood pressure intervention (P = .422).

The study was a secondary analysis, so information on stroke type and location were unavailable.
 

The big picture

“Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications,” the researchers noted.

Despite these findings, the researchers suggest that patients with diabetic retinopathy receive aggressive medical management to try to reduce their stroke risk.

“It’s important for everyone with diabetes to maintain good blood glucose control, and those with established diabetic retinopathy should pay particular attention to meeting all the stroke prevention guidelines that are established by the American Stroke Association,” said Mr. Wong.

“Patients with established diabetic retinopathy should pay particular attention to meeting all stroke prevention guidelines established by the [American Heart Association],” he added.

Mr. Wong and colleagues would like to expand on these findings. Pending grant application and funding support, they propose conducting a prospective, observational trial in stroke patients with baseline diabetic retinopathy. One aim would be to identify the most common mechanisms leading to stroke in this population, “which would have important implications for prevention efforts,” he said.
 

Consistent Findings

“The results of the study showing that having diabetic retinopathy is also associated with an increase in stroke really isn’t surprising. There have been other studies, population-based studies, done in the past, that have found a similar relationship,” Larry B. Goldstein, MD, said in a video commentary on the findings.

“The results are actually quite consistent with several other studies that have evaluated the same relationship,” added Dr. Goldstein, who is chair of the department of neurology and codirector of the Kentucky Neuroscience Institute, University of Kentucky HealthCare, Lexington.

Mr. Wong and Dr. Goldstein have disclosed no relevant financial relationships. The NIH’s National Institute of Neurological Disorders and Stroke funded the study.

This article first appeared on Medscape.com.

LOS ANGELES – Evidence continues to mount that diabetic retinopathy predicts elevated risk for stroke.

In a new study with nearly 3,000 people, those with diabetic retinopathy were 60% more likely than others with diabetes to develop an incident stroke over time. Investigators also found that addressing glucose, lipids, and blood pressure levels did not mitigate this risk in this secondary analysis of the ACCORD Eye Study.

“We are not surprised with the finding that diabetic retinopathy increases the risk of stroke — as diabetic retinopathy is common microvascular disease that is an established risk factor for cardiovascular disease,” lead author Ka-Ho Wong, BS, MBA, said in an interview.

However, “we were surprised that none of the trial interventions mitigated this risk, in particular the intensive blood pressure reduction, because hypertension is the most important cause of microvascular disease,” he said. Mr. Wong is clinical research coordinator and lab manager of the de Havenon Lab at the University of Utah Health Hospitals and Clinics in Salt Lake City.

The study findings were released Feb. 12, 2020, in advance of formal presentation at the International Stroke Conference sponsored by the American Heart Association.
 

Common predictor of vascular disease

Diabetic retinopathy is the most common complication of diabetes mellitus, affecting up to 50% of people living with type 1 and type 2 diabetes. In addition, previous research suggests that macrovascular diabetes complications, including stroke, could share a common or synergistic pathway.

This small vessel damage in the eye also has been linked to an increased risk of adverse cardiac events, including heart failure, as previously reported by Medscape Medical News.

To find out more, Mr. Wong and colleagues analyzed 2,828 participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study. They compared the stroke risk between 874 people with diabetic retinopathy and another 1,954 diabetics without this complication. The average age was 62 years and 62% were men.

Diabetic neuropathy at baseline was diagnosed using the Early Treatment Diabetic Retinopathy Study Severity Scale using seven-field stereoscopic fundus photographs.

A total of 117 participants experienced a stroke during a mean follow-up of 5.4 years.

The investigators found that diabetic retinopathy was more common among patients who had a stroke (41%) versus 31% of those without a stroke (P = .016). The link between diabetic retinopathy and stroke remained in an analysis adjusted for multiple factors, including baseline age, gender, race, total cholesterol, A_1c, smoking, and more. Risk remained elevated, with a hazard ratio of 1.60 (95% confidence interval, 1.10-2.32; P = .015).

Regarding the potential for modifying this risk, the association was unaffected among participants randomly assigned to the ACCORD glucose intervention (P = .305), lipid intervention (P = .546), or blood pressure intervention (P = .422).

The study was a secondary analysis, so information on stroke type and location were unavailable.
 

The big picture

“Diabetic retinopathy is associated with an increased risk of stroke, which suggests that the microvascular pathology inherent to diabetic retinopathy has larger cardiovascular implications,” the researchers noted.

Despite these findings, the researchers suggest that patients with diabetic retinopathy receive aggressive medical management to try to reduce their stroke risk.

“It’s important for everyone with diabetes to maintain good blood glucose control, and those with established diabetic retinopathy should pay particular attention to meeting all the stroke prevention guidelines that are established by the American Stroke Association,” said Mr. Wong.

“Patients with established diabetic retinopathy should pay particular attention to meeting all stroke prevention guidelines established by the [American Heart Association],” he added.

Mr. Wong and colleagues would like to expand on these findings. Pending grant application and funding support, they propose conducting a prospective, observational trial in stroke patients with baseline diabetic retinopathy. One aim would be to identify the most common mechanisms leading to stroke in this population, “which would have important implications for prevention efforts,” he said.
 

Consistent Findings

“The results of the study showing that having diabetic retinopathy is also associated with an increase in stroke really isn’t surprising. There have been other studies, population-based studies, done in the past, that have found a similar relationship,” Larry B. Goldstein, MD, said in a video commentary on the findings.

“The results are actually quite consistent with several other studies that have evaluated the same relationship,” added Dr. Goldstein, who is chair of the department of neurology and codirector of the Kentucky Neuroscience Institute, University of Kentucky HealthCare, Lexington.

Mr. Wong and Dr. Goldstein have disclosed no relevant financial relationships. The NIH’s National Institute of Neurological Disorders and Stroke funded the study.

This article first appeared on Medscape.com.

LOS ANGELES – Carotid artery stenting in older, asymptomatic patients with severe carotid artery stenosis is, in general, as bad an idea as it has already proven to be in symptomatic patients, with a multifold increase in adverse short- and mid-term outcomes, compared with similar older, asymptomatic patients who underwent endarterectomy, according to a combined-study analysis with more than 2,500 patients.

Mitchel L. Zoler/MDedge News

The risk for poor outcomes in patients with severe but asymptomatic carotid artery disease who underwent carotid artery stenting (CAS), compared with patients who instead underwent carotid endarterectomy (CEA) “abruptly increased around age 75,” in an analysis that combined data from the two major, published, randomized trials that compared these two interventions in this patient population, Jenifer H. Voeks, PhD said at the International Stroke Conference sponsored by the American Heart Association.

These results “largely mirror” the findings from a similar combined analysis of data from four major, randomized trials that compared CEA and CAS in patients with symptomatic carotid disease, she noted (Lancet. 2016 Mar 26;387[10025]:1305-11). The new findings in an expanded population of asymptomatic patients derived from two separate studies showed that, in patients aged 70 years or less, “CAS appears to be a reasonable alternative to CEA, but above age 70, and certainly above age 75, age-related risk factors such as cerebrovascular anatomy and underlying cerebral pathology should be carefully considered before selecting patients for CAS,” said Dr. Voeks, a neurology researcher at the Medical University of South Carolina, Charleston. Many experts also believe that, for asymptomatic patients, intensive medical management may have returned as an alternative to either of these invasive approaches for treating severe carotid stenosis and has achieved a level of equipoise that led to the launch of CREST 2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial). CREST 2 is comparing CEA and CAS with medical management, and is scheduled to report results in 2021.

The data for this analysis in asymptomatic patients came from the first CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial; N Engl J Med. 2010 Jul 1;363[1]:11-23), which included 1,181 asymptomatic patients (nearly half the total enrollment, with symptomatic patients making up the balance) and had no age ceiling, as well as all 1,453 patients from the ACT 1 trial, which enrolled exclusively asymptomatic patients and limited enrollment to patients aged 79 years or less (N Engl J Med. 2016 Mar 17;374[11]: 1011-20). Because the maximum age of patients in ACT 1 was 79 years, for this analysis Dr. Voeks and associates only included the 1,091 asymptomatic CREST patients who also were within the same age ceiling. The resulting cohort of 2,544 included 1,637 patients who underwent CAS and 907 who underwent CEA (because of a 3:1 randomization ratio in ACT 1), creating the largest data set to compare CAS and CEA by age in asymptomatic patients, Dr. Voeks noted. When subdivided by age, 30% of the cohort was younger that 65 years, 54% were 65-74, and 16% were 75-79.

The primary outcome the researchers used for their analysis was the combined incidence of periprocedural stroke, MI, or death, plus the incidence of ipsilateral stroke during 4 years of follow-up post procedure. Among patients who underwent CAS, this outcome occurred in roughly 9% of patients aged 75-79 years and in about 3% of those younger than 65 years, a hazard ratio of 2.9 that was statistically significant. In contrast, the incidence of the primary outcome among patients aged 65-74 years was just 30% higher, compared with patients aged less than 65 years, a difference that was not statistically significant.

Patients who underwent CEA showed no similar relationship between age and outcome. The incidence of the primary outcome among the CEA patients was roughly the same, about 3.5%, regardless of their age.

A second analysis that considered age as a continuous variable showed a sharply spiked increase in the risk for CAS patients, compared with CEA patients once they reached about age 73-75 years. Until about age 72, the rate of the primary outcome was nearly the same regardless of whether patients underwent CAS or CEA, but the risk for adverse outcomes rose “steeply” starting at about age 75 so that by age 79 the rate of the primary outcome approached 300% higher among the CAS patients compared with CEA patients, Dr. Voeks said.

She cautioned that the analysis included just 115 total primary-outcome events, which makes the incidence rate estimates somewhat imprecise, and that the data reflect outcomes in patients who were treated more than a decade ago, but these data remain the only reported results from large randomized trials that compared CAS and CEA in asymptomatic patients.

Dr. Voeks reported no disclosures.

mzoler@mdedge.com

SOURCE: Voeks JH al. Stroke. 2020 Feb 12;51[suppl 1], Abstract 70.

LOS ANGELES – Carotid artery stenting in older, asymptomatic patients with severe carotid artery stenosis is, in general, as bad an idea as it has already proven to be in symptomatic patients, with a multifold increase in adverse short- and mid-term outcomes, compared with similar older, asymptomatic patients who underwent endarterectomy, according to a combined-study analysis with more than 2,500 patients.

Mitchel L. Zoler/MDedge News

The risk for poor outcomes in patients with severe but asymptomatic carotid artery disease who underwent carotid artery stenting (CAS), compared with patients who instead underwent carotid endarterectomy (CEA) “abruptly increased around age 75,” in an analysis that combined data from the two major, published, randomized trials that compared these two interventions in this patient population, Jenifer H. Voeks, PhD said at the International Stroke Conference sponsored by the American Heart Association.

These results “largely mirror” the findings from a similar combined analysis of data from four major, randomized trials that compared CEA and CAS in patients with symptomatic carotid disease, she noted (Lancet. 2016 Mar 26;387[10025]:1305-11). The new findings in an expanded population of asymptomatic patients derived from two separate studies showed that, in patients aged 70 years or less, “CAS appears to be a reasonable alternative to CEA, but above age 70, and certainly above age 75, age-related risk factors such as cerebrovascular anatomy and underlying cerebral pathology should be carefully considered before selecting patients for CAS,” said Dr. Voeks, a neurology researcher at the Medical University of South Carolina, Charleston. Many experts also believe that, for asymptomatic patients, intensive medical management may have returned as an alternative to either of these invasive approaches for treating severe carotid stenosis and has achieved a level of equipoise that led to the launch of CREST 2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial). CREST 2 is comparing CEA and CAS with medical management, and is scheduled to report results in 2021.

The data for this analysis in asymptomatic patients came from the first CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial; N Engl J Med. 2010 Jul 1;363[1]:11-23), which included 1,181 asymptomatic patients (nearly half the total enrollment, with symptomatic patients making up the balance) and had no age ceiling, as well as all 1,453 patients from the ACT 1 trial, which enrolled exclusively asymptomatic patients and limited enrollment to patients aged 79 years or less (N Engl J Med. 2016 Mar 17;374[11]: 1011-20). Because the maximum age of patients in ACT 1 was 79 years, for this analysis Dr. Voeks and associates only included the 1,091 asymptomatic CREST patients who also were within the same age ceiling. The resulting cohort of 2,544 included 1,637 patients who underwent CAS and 907 who underwent CEA (because of a 3:1 randomization ratio in ACT 1), creating the largest data set to compare CAS and CEA by age in asymptomatic patients, Dr. Voeks noted. When subdivided by age, 30% of the cohort was younger that 65 years, 54% were 65-74, and 16% were 75-79.

The primary outcome the researchers used for their analysis was the combined incidence of periprocedural stroke, MI, or death, plus the incidence of ipsilateral stroke during 4 years of follow-up post procedure. Among patients who underwent CAS, this outcome occurred in roughly 9% of patients aged 75-79 years and in about 3% of those younger than 65 years, a hazard ratio of 2.9 that was statistically significant. In contrast, the incidence of the primary outcome among patients aged 65-74 years was just 30% higher, compared with patients aged less than 65 years, a difference that was not statistically significant.

Patients who underwent CEA showed no similar relationship between age and outcome. The incidence of the primary outcome among the CEA patients was roughly the same, about 3.5%, regardless of their age.

A second analysis that considered age as a continuous variable showed a sharply spiked increase in the risk for CAS patients, compared with CEA patients once they reached about age 73-75 years. Until about age 72, the rate of the primary outcome was nearly the same regardless of whether patients underwent CAS or CEA, but the risk for adverse outcomes rose “steeply” starting at about age 75 so that by age 79 the rate of the primary outcome approached 300% higher among the CAS patients compared with CEA patients, Dr. Voeks said.

She cautioned that the analysis included just 115 total primary-outcome events, which makes the incidence rate estimates somewhat imprecise, and that the data reflect outcomes in patients who were treated more than a decade ago, but these data remain the only reported results from large randomized trials that compared CAS and CEA in asymptomatic patients.

Dr. Voeks reported no disclosures.

mzoler@mdedge.com

SOURCE: Voeks JH al. Stroke. 2020 Feb 12;51[suppl 1], Abstract 70.

LOS ANGELES – Carotid artery stenting in older, asymptomatic patients with severe carotid artery stenosis is, in general, as bad an idea as it has already proven to be in symptomatic patients, with a multifold increase in adverse short- and mid-term outcomes, compared with similar older, asymptomatic patients who underwent endarterectomy, according to a combined-study analysis with more than 2,500 patients.

Mitchel L. Zoler/MDedge News

The risk for poor outcomes in patients with severe but asymptomatic carotid artery disease who underwent carotid artery stenting (CAS), compared with patients who instead underwent carotid endarterectomy (CEA) “abruptly increased around age 75,” in an analysis that combined data from the two major, published, randomized trials that compared these two interventions in this patient population, Jenifer H. Voeks, PhD said at the International Stroke Conference sponsored by the American Heart Association.

These results “largely mirror” the findings from a similar combined analysis of data from four major, randomized trials that compared CEA and CAS in patients with symptomatic carotid disease, she noted (Lancet. 2016 Mar 26;387[10025]:1305-11). The new findings in an expanded population of asymptomatic patients derived from two separate studies showed that, in patients aged 70 years or less, “CAS appears to be a reasonable alternative to CEA, but above age 70, and certainly above age 75, age-related risk factors such as cerebrovascular anatomy and underlying cerebral pathology should be carefully considered before selecting patients for CAS,” said Dr. Voeks, a neurology researcher at the Medical University of South Carolina, Charleston. Many experts also believe that, for asymptomatic patients, intensive medical management may have returned as an alternative to either of these invasive approaches for treating severe carotid stenosis and has achieved a level of equipoise that led to the launch of CREST 2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial). CREST 2 is comparing CEA and CAS with medical management, and is scheduled to report results in 2021.

The data for this analysis in asymptomatic patients came from the first CREST (Carotid Revascularization Endarterectomy Versus Stenting Trial; N Engl J Med. 2010 Jul 1;363[1]:11-23), which included 1,181 asymptomatic patients (nearly half the total enrollment, with symptomatic patients making up the balance) and had no age ceiling, as well as all 1,453 patients from the ACT 1 trial, which enrolled exclusively asymptomatic patients and limited enrollment to patients aged 79 years or less (N Engl J Med. 2016 Mar 17;374[11]: 1011-20). Because the maximum age of patients in ACT 1 was 79 years, for this analysis Dr. Voeks and associates only included the 1,091 asymptomatic CREST patients who also were within the same age ceiling. The resulting cohort of 2,544 included 1,637 patients who underwent CAS and 907 who underwent CEA (because of a 3:1 randomization ratio in ACT 1), creating the largest data set to compare CAS and CEA by age in asymptomatic patients, Dr. Voeks noted. When subdivided by age, 30% of the cohort was younger that 65 years, 54% were 65-74, and 16% were 75-79.

The primary outcome the researchers used for their analysis was the combined incidence of periprocedural stroke, MI, or death, plus the incidence of ipsilateral stroke during 4 years of follow-up post procedure. Among patients who underwent CAS, this outcome occurred in roughly 9% of patients aged 75-79 years and in about 3% of those younger than 65 years, a hazard ratio of 2.9 that was statistically significant. In contrast, the incidence of the primary outcome among patients aged 65-74 years was just 30% higher, compared with patients aged less than 65 years, a difference that was not statistically significant.

Patients who underwent CEA showed no similar relationship between age and outcome. The incidence of the primary outcome among the CEA patients was roughly the same, about 3.5%, regardless of their age.

A second analysis that considered age as a continuous variable showed a sharply spiked increase in the risk for CAS patients, compared with CEA patients once they reached about age 73-75 years. Until about age 72, the rate of the primary outcome was nearly the same regardless of whether patients underwent CAS or CEA, but the risk for adverse outcomes rose “steeply” starting at about age 75 so that by age 79 the rate of the primary outcome approached 300% higher among the CAS patients compared with CEA patients, Dr. Voeks said.

She cautioned that the analysis included just 115 total primary-outcome events, which makes the incidence rate estimates somewhat imprecise, and that the data reflect outcomes in patients who were treated more than a decade ago, but these data remain the only reported results from large randomized trials that compared CAS and CEA in asymptomatic patients.

Dr. Voeks reported no disclosures.

mzoler@mdedge.com

SOURCE: Voeks JH al. Stroke. 2020 Feb 12;51[suppl 1], Abstract 70.

News that the United States Medical Licensing Examination (USMLE) program will change its Step 1 scoring from a 3-digit number to pass/fail starting Jan. 1, 2022, has set off a flurry of shocked responses from students and physicians.

J. Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School in Norfolk, said in an interview that he was “stunned” when he heard the news on Wednesday and said the switch presents “the single biggest opportunity for medical school education reform since the Flexner Report,” which in 1910 established standards for modern medical education.

Numbers will continue for some tests

The USMLE cosponsors – the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME) – said that the Step 2 Clinical Knowledge (CK) exam and Step 3 will continue to be scored numerically. Step 2 Clinical Skills (CS) will continue its pass/fail system.

The change was made after Step 1 had been roundly criticized as playing too big a role in the process of becoming a physician and for causing students to study for the test instead of engaging fully in their medical education.

Ramie Fathy, a third-year medical student at the University of Pennsylvania, Philadelphia, currently studying for Step 1, said in an interview that it would have been nice personally to have the pass/fail choice, but he predicts both good and unintended consequences in the change.

The positive news, Mr. Fathy said, is that less emphasis will be put on the Step 1 test, which includes memorizing basic science details that may or not be relevant depending on later specialty choice.

“It’s not necessarily measuring what the test makers intended, which was whether or not a student can understand and apply basic science concepts to the practice of medicine,” he said.

“The current system encourages students to get as high a score as possible, which – after a certain point – translates to memorizing many little details that become increasingly less practically relevant,” Mr. Fathy said.

Pressure may move elsewhere?

However, Mr. Fathy worries that, without a scoring system to help decide who stands out in Step 1, residency program directors will depend more on the reputation of candidates’ medical school and the clout of the person writing a letter of recommendation – factors that are often influenced by family resources and social standing. That could wedge a further economic divide into the path to becoming a physician.

Mr. Fathy said he and fellow students are watching for information on what the passing bar will be and what happens with Step 2 Clinical Knowledge exam. USMLE has promised more information as soon as it is available.

“The question is whether that test will replace Step 1 as the standardized metric of student competency,” Mr. Fathy said, which would put more pressure on students further down the medical path.

Will Step 2 anxiety increase?

Dr. Carmody agreed that there is the danger that students now will spend their time studying for Step 2 CK at the expense of other parts of their education.

Meaningful reform will depend on the pass/fail move being coupled with other reforms, most importantly application caps, said Dr. Carmody, who teaches preclinical medical students and works with the residency program.

He has been blogging about Step 1 pass/fail for the past year.

Currently students can apply for as many residencies as they can pay for and Carmody said the number of applications per student has been rising over the past decade.

“That puts program directors under an impossible burden,” he said. “With our Step 1-based system, there’s significant inequality in the number of interviews people get. Programs end up overinviting the same group of people who look good on paper.”

People outside that group respond by sending more applications than they need to just to get a few interviews, Dr. Carmody added.

With caps, students would have an incentive to apply to only those programs in which they had a sincere interest, he said. Program directors also would then be better able to evaluate each application.

Switching Step 1 to pass/fail may have some effect on medical school burnout, Dr. Carmody said.

“It’s one thing to work hard when you’re on call and your patients depend on it,” he said. “But I would have a hard time staying up late every night studying something that I know in my heart is not going to help my patients, but I have to do it because I have to do better than the person who’s studying in the apartment next to me.”

Test has strayed from original purpose

Joseph Safdieh, MD, an assistant dean for clinical curriculum and director of the medical student neurology clerkship for the Weill Cornell Medicine, New York, sees the move as positive overall.

“We should not be using any single metric to define or describe our students’ overall profile,” he said in an interview.

“This has been a very significant anxiety point for our medical students for quite a number of years,” Dr. Safdieh said. “They were frustrated that their entire 4 years of medical school seemingly came down to one number.”

The test was created originally as one of three parts of licensure, he pointed out.

“Over the past 10 or 15 years, the exam has morphed to become a litmus test for very specific residency programs,” he said.

However, Dr. Safdieh has concerns that Step 2 will cultivate the same anxiety and may get too big a spotlight without the Step 1 metric, “although one could argue that test does more accurately reflect clinical material,” he said.

He also worries that students who have selected a specialty by the time they take Step 2 may find late in the game that they are less competitive in their field than they thought they were and may have to make a last-minute switch.

Dr. Safdieh said he thinks Step 2 will be next to go the pass/fail route. In reading between the lines of the announcement, he believes the test cosponsors didn’t make both pass/fail at once because it would have been “a nuclear bomb to the system.”

He credited the cosponsors with making what he called a “bold and momentous decision to initiate radical change in the overall transition between undergraduate and graduate medical education.”

Dr. Safdieh added that few in medicine were expecting Wednesday’s announcement.

“I think many of us were expecting them to go to quartile grading, not to go this far,” he said.

Dr. Safdieh suggested that, among those who may see downstream effects from the pass/fail move are offshore schools, such as those in the Caribbean. “Those schools rely on Step 1 to demonstrate that their students are meeting the rigor,” he said. But he hopes that this will lead to more holistic review.

“We’re hoping that this will force change in the system so that residency directors will look at more than just test-taking ability. They’ll look at publications and scholarship, community service and advocacy and performance in medical school,” Dr. Safdieh said.

Alison J. Whelan, MD, chief medical education officer of the Association of American Medical Colleges said in a statement, “The transition from medical school to residency training is a matter of great concern throughout academic medicine.

“The decision by the NBME and FSMB to change USMLE Step 1 score reporting to pass/fail was very carefully considered to balance student learning and student well-being,” she said. “The medical education community must now work together to identify and implement additional changes to improve the overall UME-GME [undergraduate and graduate medical education] transition system for all stakeholders and the AAMC is committed to helping lead this work.”

Dr. Fathy, Dr. Carmody, and Dr. Safdieh have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

News that the United States Medical Licensing Examination (USMLE) program will change its Step 1 scoring from a 3-digit number to pass/fail starting Jan. 1, 2022, has set off a flurry of shocked responses from students and physicians.

J. Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School in Norfolk, said in an interview that he was “stunned” when he heard the news on Wednesday and said the switch presents “the single biggest opportunity for medical school education reform since the Flexner Report,” which in 1910 established standards for modern medical education.

Numbers will continue for some tests

The USMLE cosponsors – the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME) – said that the Step 2 Clinical Knowledge (CK) exam and Step 3 will continue to be scored numerically. Step 2 Clinical Skills (CS) will continue its pass/fail system.

The change was made after Step 1 had been roundly criticized as playing too big a role in the process of becoming a physician and for causing students to study for the test instead of engaging fully in their medical education.

Ramie Fathy, a third-year medical student at the University of Pennsylvania, Philadelphia, currently studying for Step 1, said in an interview that it would have been nice personally to have the pass/fail choice, but he predicts both good and unintended consequences in the change.

The positive news, Mr. Fathy said, is that less emphasis will be put on the Step 1 test, which includes memorizing basic science details that may or not be relevant depending on later specialty choice.

“It’s not necessarily measuring what the test makers intended, which was whether or not a student can understand and apply basic science concepts to the practice of medicine,” he said.

“The current system encourages students to get as high a score as possible, which – after a certain point – translates to memorizing many little details that become increasingly less practically relevant,” Mr. Fathy said.

Pressure may move elsewhere?

However, Mr. Fathy worries that, without a scoring system to help decide who stands out in Step 1, residency program directors will depend more on the reputation of candidates’ medical school and the clout of the person writing a letter of recommendation – factors that are often influenced by family resources and social standing. That could wedge a further economic divide into the path to becoming a physician.

Mr. Fathy said he and fellow students are watching for information on what the passing bar will be and what happens with Step 2 Clinical Knowledge exam. USMLE has promised more information as soon as it is available.

“The question is whether that test will replace Step 1 as the standardized metric of student competency,” Mr. Fathy said, which would put more pressure on students further down the medical path.

Will Step 2 anxiety increase?

Dr. Carmody agreed that there is the danger that students now will spend their time studying for Step 2 CK at the expense of other parts of their education.

Meaningful reform will depend on the pass/fail move being coupled with other reforms, most importantly application caps, said Dr. Carmody, who teaches preclinical medical students and works with the residency program.

He has been blogging about Step 1 pass/fail for the past year.

Currently students can apply for as many residencies as they can pay for and Carmody said the number of applications per student has been rising over the past decade.

“That puts program directors under an impossible burden,” he said. “With our Step 1-based system, there’s significant inequality in the number of interviews people get. Programs end up overinviting the same group of people who look good on paper.”

People outside that group respond by sending more applications than they need to just to get a few interviews, Dr. Carmody added.

With caps, students would have an incentive to apply to only those programs in which they had a sincere interest, he said. Program directors also would then be better able to evaluate each application.

Switching Step 1 to pass/fail may have some effect on medical school burnout, Dr. Carmody said.

“It’s one thing to work hard when you’re on call and your patients depend on it,” he said. “But I would have a hard time staying up late every night studying something that I know in my heart is not going to help my patients, but I have to do it because I have to do better than the person who’s studying in the apartment next to me.”

Test has strayed from original purpose

Joseph Safdieh, MD, an assistant dean for clinical curriculum and director of the medical student neurology clerkship for the Weill Cornell Medicine, New York, sees the move as positive overall.

“We should not be using any single metric to define or describe our students’ overall profile,” he said in an interview.

“This has been a very significant anxiety point for our medical students for quite a number of years,” Dr. Safdieh said. “They were frustrated that their entire 4 years of medical school seemingly came down to one number.”

The test was created originally as one of three parts of licensure, he pointed out.

“Over the past 10 or 15 years, the exam has morphed to become a litmus test for very specific residency programs,” he said.

However, Dr. Safdieh has concerns that Step 2 will cultivate the same anxiety and may get too big a spotlight without the Step 1 metric, “although one could argue that test does more accurately reflect clinical material,” he said.

He also worries that students who have selected a specialty by the time they take Step 2 may find late in the game that they are less competitive in their field than they thought they were and may have to make a last-minute switch.

Dr. Safdieh said he thinks Step 2 will be next to go the pass/fail route. In reading between the lines of the announcement, he believes the test cosponsors didn’t make both pass/fail at once because it would have been “a nuclear bomb to the system.”

He credited the cosponsors with making what he called a “bold and momentous decision to initiate radical change in the overall transition between undergraduate and graduate medical education.”

Dr. Safdieh added that few in medicine were expecting Wednesday’s announcement.

“I think many of us were expecting them to go to quartile grading, not to go this far,” he said.

Dr. Safdieh suggested that, among those who may see downstream effects from the pass/fail move are offshore schools, such as those in the Caribbean. “Those schools rely on Step 1 to demonstrate that their students are meeting the rigor,” he said. But he hopes that this will lead to more holistic review.

“We’re hoping that this will force change in the system so that residency directors will look at more than just test-taking ability. They’ll look at publications and scholarship, community service and advocacy and performance in medical school,” Dr. Safdieh said.

Alison J. Whelan, MD, chief medical education officer of the Association of American Medical Colleges said in a statement, “The transition from medical school to residency training is a matter of great concern throughout academic medicine.

“The decision by the NBME and FSMB to change USMLE Step 1 score reporting to pass/fail was very carefully considered to balance student learning and student well-being,” she said. “The medical education community must now work together to identify and implement additional changes to improve the overall UME-GME [undergraduate and graduate medical education] transition system for all stakeholders and the AAMC is committed to helping lead this work.”

Dr. Fathy, Dr. Carmody, and Dr. Safdieh have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

News that the United States Medical Licensing Examination (USMLE) program will change its Step 1 scoring from a 3-digit number to pass/fail starting Jan. 1, 2022, has set off a flurry of shocked responses from students and physicians.

J. Bryan Carmody, MD, MPH, an assistant professor at Eastern Virginia Medical School in Norfolk, said in an interview that he was “stunned” when he heard the news on Wednesday and said the switch presents “the single biggest opportunity for medical school education reform since the Flexner Report,” which in 1910 established standards for modern medical education.

Numbers will continue for some tests

The USMLE cosponsors – the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME) – said that the Step 2 Clinical Knowledge (CK) exam and Step 3 will continue to be scored numerically. Step 2 Clinical Skills (CS) will continue its pass/fail system.

The change was made after Step 1 had been roundly criticized as playing too big a role in the process of becoming a physician and for causing students to study for the test instead of engaging fully in their medical education.

Ramie Fathy, a third-year medical student at the University of Pennsylvania, Philadelphia, currently studying for Step 1, said in an interview that it would have been nice personally to have the pass/fail choice, but he predicts both good and unintended consequences in the change.

The positive news, Mr. Fathy said, is that less emphasis will be put on the Step 1 test, which includes memorizing basic science details that may or not be relevant depending on later specialty choice.

“It’s not necessarily measuring what the test makers intended, which was whether or not a student can understand and apply basic science concepts to the practice of medicine,” he said.

“The current system encourages students to get as high a score as possible, which – after a certain point – translates to memorizing many little details that become increasingly less practically relevant,” Mr. Fathy said.

Pressure may move elsewhere?

However, Mr. Fathy worries that, without a scoring system to help decide who stands out in Step 1, residency program directors will depend more on the reputation of candidates’ medical school and the clout of the person writing a letter of recommendation – factors that are often influenced by family resources and social standing. That could wedge a further economic divide into the path to becoming a physician.

Mr. Fathy said he and fellow students are watching for information on what the passing bar will be and what happens with Step 2 Clinical Knowledge exam. USMLE has promised more information as soon as it is available.

“The question is whether that test will replace Step 1 as the standardized metric of student competency,” Mr. Fathy said, which would put more pressure on students further down the medical path.

Will Step 2 anxiety increase?

Dr. Carmody agreed that there is the danger that students now will spend their time studying for Step 2 CK at the expense of other parts of their education.

Meaningful reform will depend on the pass/fail move being coupled with other reforms, most importantly application caps, said Dr. Carmody, who teaches preclinical medical students and works with the residency program.

He has been blogging about Step 1 pass/fail for the past year.

Currently students can apply for as many residencies as they can pay for and Carmody said the number of applications per student has been rising over the past decade.

“That puts program directors under an impossible burden,” he said. “With our Step 1-based system, there’s significant inequality in the number of interviews people get. Programs end up overinviting the same group of people who look good on paper.”

People outside that group respond by sending more applications than they need to just to get a few interviews, Dr. Carmody added.

With caps, students would have an incentive to apply to only those programs in which they had a sincere interest, he said. Program directors also would then be better able to evaluate each application.

Switching Step 1 to pass/fail may have some effect on medical school burnout, Dr. Carmody said.

“It’s one thing to work hard when you’re on call and your patients depend on it,” he said. “But I would have a hard time staying up late every night studying something that I know in my heart is not going to help my patients, but I have to do it because I have to do better than the person who’s studying in the apartment next to me.”

Test has strayed from original purpose

Joseph Safdieh, MD, an assistant dean for clinical curriculum and director of the medical student neurology clerkship for the Weill Cornell Medicine, New York, sees the move as positive overall.

“We should not be using any single metric to define or describe our students’ overall profile,” he said in an interview.

“This has been a very significant anxiety point for our medical students for quite a number of years,” Dr. Safdieh said. “They were frustrated that their entire 4 years of medical school seemingly came down to one number.”

The test was created originally as one of three parts of licensure, he pointed out.

“Over the past 10 or 15 years, the exam has morphed to become a litmus test for very specific residency programs,” he said.

However, Dr. Safdieh has concerns that Step 2 will cultivate the same anxiety and may get too big a spotlight without the Step 1 metric, “although one could argue that test does more accurately reflect clinical material,” he said.

He also worries that students who have selected a specialty by the time they take Step 2 may find late in the game that they are less competitive in their field than they thought they were and may have to make a last-minute switch.

Dr. Safdieh said he thinks Step 2 will be next to go the pass/fail route. In reading between the lines of the announcement, he believes the test cosponsors didn’t make both pass/fail at once because it would have been “a nuclear bomb to the system.”

He credited the cosponsors with making what he called a “bold and momentous decision to initiate radical change in the overall transition between undergraduate and graduate medical education.”

Dr. Safdieh added that few in medicine were expecting Wednesday’s announcement.

“I think many of us were expecting them to go to quartile grading, not to go this far,” he said.

Dr. Safdieh suggested that, among those who may see downstream effects from the pass/fail move are offshore schools, such as those in the Caribbean. “Those schools rely on Step 1 to demonstrate that their students are meeting the rigor,” he said. But he hopes that this will lead to more holistic review.

“We’re hoping that this will force change in the system so that residency directors will look at more than just test-taking ability. They’ll look at publications and scholarship, community service and advocacy and performance in medical school,” Dr. Safdieh said.

Alison J. Whelan, MD, chief medical education officer of the Association of American Medical Colleges said in a statement, “The transition from medical school to residency training is a matter of great concern throughout academic medicine.

“The decision by the NBME and FSMB to change USMLE Step 1 score reporting to pass/fail was very carefully considered to balance student learning and student well-being,” she said. “The medical education community must now work together to identify and implement additional changes to improve the overall UME-GME [undergraduate and graduate medical education] transition system for all stakeholders and the AAMC is committed to helping lead this work.”

Dr. Fathy, Dr. Carmody, and Dr. Safdieh have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

SNOWMASS, COLO. – Catheter ablation of atrial fibrillation was associated with a significant reduction in the composite endpoint of all-cause mortality, stroke, major bleeding, or cardiac arrest, compared with rhythm and/or rate control drugs in a propensity score–weighted, retrospective, observational study.

Bruce Jancin/MDedge News

Findings of the investigation, which included more than 183,000 real-world patients in routine clinical practice, were reported by Peter S. Noseworthy, MD, during the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

The results breathe new life into the controversy created by the previously reported CABANA trial (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation), a 10-country study in which 2,204 patients with atrial fibrillation (AFib) were randomized to catheter ablation or antiarrhythmic and/or rhythm control medications and followed for a mean of about 4 years. CABANA yielded a negative result (JAMA. 2019 Apr 2;321[13]:1261-74), with the prespecified intent-to-treat analysis indicating no significant between-group difference in the primary composite endpoint – the very same one that was positive in the large observational study.

However, CABANA was marred by major problems arising from protocol deviations: Nearly 28% of patients assigned to medical therapy crossed over to catheter ablation, typically because their antiarrhythmic drugs failed, and 10% of patients randomized to catheter ablation never got it. This muddies the waters when trying to identify a true stroke/mortality benefit for catheter ablation, if indeed any such benefit was actually present.

Here’s where the controversy arose: While CABANA must be called a negative trial based upon the disappointing results of the intent-to-treat analysis, a prespecified post hoc analysis of patients as actually treated showed a statistically significant 27% relative risk reduction for the primary composite endpoint in the catheter ablation group. That’s strikingly similar to the 30% relative risk reduction for catheter ablation seen in the huge observational study, where the CABANA-type primary outcome occurred in 22.5% of the medically managed patients and 16.8% of those who underwent catheter ablation, noted Dr. Noseworthy, professor of medicine and director of heart rhythm and physiology at the Mayo Clinic in Rochester, Minn.

He ought to know: He was both an investigator in CABANA and first author of the published observational study (Eur Heart J. 2019 Apr 21;40[16]:1257-64).

In the observational study, Dr. Noseworthy and coinvestigators utilized a huge U.S. administrative health claims database in order to identify a nationally representative group of 183,760 AFib patients, 12,032 of whom were treated with catheter ablation and the rest with antiarrhythmic and/or rhythm control drugs during the same years the CABANA trial was enrolling patients. The two groups were balanced using propensity score weighting to adjust for baseline differences in 90 variables.

The investigators sought to learn if the CABANA study population was representative of real-world AFib patients, and whether the observational experience could help resolve the CABANA controversy. It turned out that most AFib patients seen in daily clinical practice were CABANA like; that is, 74% of them would have been eligible for the clinical trial because they were symptomatic, over age 65, or younger than 65 with at least one CHADS2 stroke risk factor. About 22% of the large real-world sample would have been excluded from CABANA because they’d failed on amiodarone and other antiarrhythmic agents or had previously undergone ablation. About 4% of patients failed to meet the CABANA inclusion criteria.

The risk reduction for the composite endpoint associated with catheter ablation in the large retrospective study was greatest in the CABANA-like patients, at 30%. It was less robust but still statistically significant at 15% in patients who met at least one of the exclusion criteria for the trial.

The sheer size of this study provides greater statistical power than in CABANA. Of course, a nonrandomized, propensity score–based comparison such as this is always susceptible to confounding, even after adjustment for 90 variables. But the observational study does offer “a glimmer of hope” that catheter ablation, done in the right patients, might confer a stroke risk reduction and mortality benefit, he said.

The 33% relative risk reduction in the small group of real-world patients who failed to meet the CABANA inclusion criteria, while numerically impressive, wasn’t close to statistical significance, probably because event rates in that population were so low.

“Even if you could reduce stroke risk with ablation in that low-risk group, it would be a very inefficient way to reduce the population burden of stroke,” Dr. Noseworthy observed.

Putting together the results of CABANA and the large observational study to sum up his view of where catheter ablation for AF[ib] stands today, Dr. Noseworthy commented, “Ablation is reasonable for symptom control in many patients, basically anyone who is either breaking through on drugs or doesn’t want to take the drugs and is highly symptomatic. And there may be a small stroke and/or mortality benefit for people who are in the sweet spot – and those are people who look a lot like the patients enrolled in CABANA.”

Patients who met the exclusion criteria for CABANA are too advanced in their AFib to be likely to derive a stroke or mortality benefit from catheter ablation. “It’s very hard to move the needle in these patients with either a drug or catheter ablation approach. I wouldn’t try to reduce the risk of stroke here with an expensive and invasive procedure,” the electrophysiologist concluded.

He reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

SNOWMASS, COLO. – Catheter ablation of atrial fibrillation was associated with a significant reduction in the composite endpoint of all-cause mortality, stroke, major bleeding, or cardiac arrest, compared with rhythm and/or rate control drugs in a propensity score–weighted, retrospective, observational study.

Bruce Jancin/MDedge News

Findings of the investigation, which included more than 183,000 real-world patients in routine clinical practice, were reported by Peter S. Noseworthy, MD, during the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

The results breathe new life into the controversy created by the previously reported CABANA trial (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation), a 10-country study in which 2,204 patients with atrial fibrillation (AFib) were randomized to catheter ablation or antiarrhythmic and/or rhythm control medications and followed for a mean of about 4 years. CABANA yielded a negative result (JAMA. 2019 Apr 2;321[13]:1261-74), with the prespecified intent-to-treat analysis indicating no significant between-group difference in the primary composite endpoint – the very same one that was positive in the large observational study.

However, CABANA was marred by major problems arising from protocol deviations: Nearly 28% of patients assigned to medical therapy crossed over to catheter ablation, typically because their antiarrhythmic drugs failed, and 10% of patients randomized to catheter ablation never got it. This muddies the waters when trying to identify a true stroke/mortality benefit for catheter ablation, if indeed any such benefit was actually present.

Here’s where the controversy arose: While CABANA must be called a negative trial based upon the disappointing results of the intent-to-treat analysis, a prespecified post hoc analysis of patients as actually treated showed a statistically significant 27% relative risk reduction for the primary composite endpoint in the catheter ablation group. That’s strikingly similar to the 30% relative risk reduction for catheter ablation seen in the huge observational study, where the CABANA-type primary outcome occurred in 22.5% of the medically managed patients and 16.8% of those who underwent catheter ablation, noted Dr. Noseworthy, professor of medicine and director of heart rhythm and physiology at the Mayo Clinic in Rochester, Minn.

He ought to know: He was both an investigator in CABANA and first author of the published observational study (Eur Heart J. 2019 Apr 21;40[16]:1257-64).

In the observational study, Dr. Noseworthy and coinvestigators utilized a huge U.S. administrative health claims database in order to identify a nationally representative group of 183,760 AFib patients, 12,032 of whom were treated with catheter ablation and the rest with antiarrhythmic and/or rhythm control drugs during the same years the CABANA trial was enrolling patients. The two groups were balanced using propensity score weighting to adjust for baseline differences in 90 variables.

The investigators sought to learn if the CABANA study population was representative of real-world AFib patients, and whether the observational experience could help resolve the CABANA controversy. It turned out that most AFib patients seen in daily clinical practice were CABANA like; that is, 74% of them would have been eligible for the clinical trial because they were symptomatic, over age 65, or younger than 65 with at least one CHADS2 stroke risk factor. About 22% of the large real-world sample would have been excluded from CABANA because they’d failed on amiodarone and other antiarrhythmic agents or had previously undergone ablation. About 4% of patients failed to meet the CABANA inclusion criteria.

The risk reduction for the composite endpoint associated with catheter ablation in the large retrospective study was greatest in the CABANA-like patients, at 30%. It was less robust but still statistically significant at 15% in patients who met at least one of the exclusion criteria for the trial.

The sheer size of this study provides greater statistical power than in CABANA. Of course, a nonrandomized, propensity score–based comparison such as this is always susceptible to confounding, even after adjustment for 90 variables. But the observational study does offer “a glimmer of hope” that catheter ablation, done in the right patients, might confer a stroke risk reduction and mortality benefit, he said.

The 33% relative risk reduction in the small group of real-world patients who failed to meet the CABANA inclusion criteria, while numerically impressive, wasn’t close to statistical significance, probably because event rates in that population were so low.

“Even if you could reduce stroke risk with ablation in that low-risk group, it would be a very inefficient way to reduce the population burden of stroke,” Dr. Noseworthy observed.

Putting together the results of CABANA and the large observational study to sum up his view of where catheter ablation for AF[ib] stands today, Dr. Noseworthy commented, “Ablation is reasonable for symptom control in many patients, basically anyone who is either breaking through on drugs or doesn’t want to take the drugs and is highly symptomatic. And there may be a small stroke and/or mortality benefit for people who are in the sweet spot – and those are people who look a lot like the patients enrolled in CABANA.”

Patients who met the exclusion criteria for CABANA are too advanced in their AFib to be likely to derive a stroke or mortality benefit from catheter ablation. “It’s very hard to move the needle in these patients with either a drug or catheter ablation approach. I wouldn’t try to reduce the risk of stroke here with an expensive and invasive procedure,” the electrophysiologist concluded.

He reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

SNOWMASS, COLO. – Catheter ablation of atrial fibrillation was associated with a significant reduction in the composite endpoint of all-cause mortality, stroke, major bleeding, or cardiac arrest, compared with rhythm and/or rate control drugs in a propensity score–weighted, retrospective, observational study.

Bruce Jancin/MDedge News

Findings of the investigation, which included more than 183,000 real-world patients in routine clinical practice, were reported by Peter S. Noseworthy, MD, during the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

The results breathe new life into the controversy created by the previously reported CABANA trial (Catheter Ablation vs. Antiarrhythmic Drug Therapy for Atrial Fibrillation), a 10-country study in which 2,204 patients with atrial fibrillation (AFib) were randomized to catheter ablation or antiarrhythmic and/or rhythm control medications and followed for a mean of about 4 years. CABANA yielded a negative result (JAMA. 2019 Apr 2;321[13]:1261-74), with the prespecified intent-to-treat analysis indicating no significant between-group difference in the primary composite endpoint – the very same one that was positive in the large observational study.

However, CABANA was marred by major problems arising from protocol deviations: Nearly 28% of patients assigned to medical therapy crossed over to catheter ablation, typically because their antiarrhythmic drugs failed, and 10% of patients randomized to catheter ablation never got it. This muddies the waters when trying to identify a true stroke/mortality benefit for catheter ablation, if indeed any such benefit was actually present.

Here’s where the controversy arose: While CABANA must be called a negative trial based upon the disappointing results of the intent-to-treat analysis, a prespecified post hoc analysis of patients as actually treated showed a statistically significant 27% relative risk reduction for the primary composite endpoint in the catheter ablation group. That’s strikingly similar to the 30% relative risk reduction for catheter ablation seen in the huge observational study, where the CABANA-type primary outcome occurred in 22.5% of the medically managed patients and 16.8% of those who underwent catheter ablation, noted Dr. Noseworthy, professor of medicine and director of heart rhythm and physiology at the Mayo Clinic in Rochester, Minn.

He ought to know: He was both an investigator in CABANA and first author of the published observational study (Eur Heart J. 2019 Apr 21;40[16]:1257-64).

In the observational study, Dr. Noseworthy and coinvestigators utilized a huge U.S. administrative health claims database in order to identify a nationally representative group of 183,760 AFib patients, 12,032 of whom were treated with catheter ablation and the rest with antiarrhythmic and/or rhythm control drugs during the same years the CABANA trial was enrolling patients. The two groups were balanced using propensity score weighting to adjust for baseline differences in 90 variables.

The investigators sought to learn if the CABANA study population was representative of real-world AFib patients, and whether the observational experience could help resolve the CABANA controversy. It turned out that most AFib patients seen in daily clinical practice were CABANA like; that is, 74% of them would have been eligible for the clinical trial because they were symptomatic, over age 65, or younger than 65 with at least one CHADS2 stroke risk factor. About 22% of the large real-world sample would have been excluded from CABANA because they’d failed on amiodarone and other antiarrhythmic agents or had previously undergone ablation. About 4% of patients failed to meet the CABANA inclusion criteria.

The risk reduction for the composite endpoint associated with catheter ablation in the large retrospective study was greatest in the CABANA-like patients, at 30%. It was less robust but still statistically significant at 15% in patients who met at least one of the exclusion criteria for the trial.

The sheer size of this study provides greater statistical power than in CABANA. Of course, a nonrandomized, propensity score–based comparison such as this is always susceptible to confounding, even after adjustment for 90 variables. But the observational study does offer “a glimmer of hope” that catheter ablation, done in the right patients, might confer a stroke risk reduction and mortality benefit, he said.

The 33% relative risk reduction in the small group of real-world patients who failed to meet the CABANA inclusion criteria, while numerically impressive, wasn’t close to statistical significance, probably because event rates in that population were so low.

“Even if you could reduce stroke risk with ablation in that low-risk group, it would be a very inefficient way to reduce the population burden of stroke,” Dr. Noseworthy observed.

Putting together the results of CABANA and the large observational study to sum up his view of where catheter ablation for AF[ib] stands today, Dr. Noseworthy commented, “Ablation is reasonable for symptom control in many patients, basically anyone who is either breaking through on drugs or doesn’t want to take the drugs and is highly symptomatic. And there may be a small stroke and/or mortality benefit for people who are in the sweet spot – and those are people who look a lot like the patients enrolled in CABANA.”

Patients who met the exclusion criteria for CABANA are too advanced in their AFib to be likely to derive a stroke or mortality benefit from catheter ablation. “It’s very hard to move the needle in these patients with either a drug or catheter ablation approach. I wouldn’t try to reduce the risk of stroke here with an expensive and invasive procedure,” the electrophysiologist concluded.

He reported having no financial conflicts regarding his presentation.

bjancin@mdedge.com

The complement C5 inhibitor zilucoplan significantly improved muscle weakness and daily functioning in patients with moderate to severe generalized myasthenia gravis (gMG), according to investigators who conducted a phase 2, randomized, placebo-controlled study of the agent.

The clinical effect of the self-administered macrocyclic peptide inhibitor was “similar,” the investigators wrote, to what was seen in studies of the intravenously administered complement inhibitor eculizumab, which is approved by the Food and Drug Administration for treatment of gMG.

While eculizumab studies were restricted to patients with refractory gMG, the investigators wrote that their study of zilucoplan included a broader population, including patients who had not failed prior therapies, who were earlier in their disease course, and who had a history of thymoma.

“This observation is important because in gMG, disease severity frequently peaks within the first few years after diagnosis, before all treatment options have been exhausted, and before patients may be formally declared treatment refractory,” wrote James F. Howard Jr, MD, of the University of North Carolina in Chapel Hill, and coauthors.

Complement inhibition is a “targeted approach” that addresses the primary mechanism of tissue damage in gMG, the investigators wrote.

That stands in contrast to conventional gMG treatments including pyridostigmine, corticosteroids, and other immunosuppressants. “These treatments lack strong evidence from clinical trials to support their efficacy, are often poorly tolerated, and can be associated with considerable long-term toxicities,” Dr. Howard and colleagues wrote in their report, which was published in JAMA Neurology.

A total of 44 adult patients with gMG were randomized to receive daily zilucoplan 0.1 mg/kg, 0.3 mg/kg, or placebo for 12 weeks in this 25-center North American study. All patients had acetylcholine receptor autoantibody–positive disease and a Quantitative Myasthenia Gravis (QMG) score of 12 or higher. The QMG score ranges from 0, indicating no muscle weakness, to 39, or severe weakness.

Per the study protocol, patients had to keep taking their current gMG medication without changing the dose.

Change in QMG score from baseline to 12 weeks, the primary efficacy endpoint of the study, showed a significant and clinically meaningful difference favoring zilucoplan 0.3 mg/kg over placebo, according to the investigators.

The mean change was –6.0 points for zilucoplan 0.3 mg/kg and –3.2 for placebo (P = .05), according to their report, which indicated a rapid onset of action apparent 1 week after starting treatment.

Zilucoplan 0.1 mg/kg also yielded a significant and clinically meaningful improvement versus placebo, but its magnitude was smaller and took 4 weeks to become apparent.

Treatment with zilucoplan also significantly improved MG Activities of Daily Living scores versus placebo, a key secondary endpoint of the trial, according to the researchers.

Treatment-emergent adverse events, which included local injection-site reactions, were mild and judged to be unrelated to the study treatment, according to the report.

Ra Pharmaceuticals funded the study. Dr. Howard reported disclosures related to Ra Pharmaceuticals, Alexion Pharmaceuticals, argenx, Viela Bio, and others.

SOURCE: Howard Jr JF et al. JAMA Neurol. 2020 Feb 17. doi: 10.1001/jamaneurol.2019.5125.

The complement C5 inhibitor zilucoplan significantly improved muscle weakness and daily functioning in patients with moderate to severe generalized myasthenia gravis (gMG), according to investigators who conducted a phase 2, randomized, placebo-controlled study of the agent.

The clinical effect of the self-administered macrocyclic peptide inhibitor was “similar,” the investigators wrote, to what was seen in studies of the intravenously administered complement inhibitor eculizumab, which is approved by the Food and Drug Administration for treatment of gMG.

While eculizumab studies were restricted to patients with refractory gMG, the investigators wrote that their study of zilucoplan included a broader population, including patients who had not failed prior therapies, who were earlier in their disease course, and who had a history of thymoma.

“This observation is important because in gMG, disease severity frequently peaks within the first few years after diagnosis, before all treatment options have been exhausted, and before patients may be formally declared treatment refractory,” wrote James F. Howard Jr, MD, of the University of North Carolina in Chapel Hill, and coauthors.

Complement inhibition is a “targeted approach” that addresses the primary mechanism of tissue damage in gMG, the investigators wrote.

That stands in contrast to conventional gMG treatments including pyridostigmine, corticosteroids, and other immunosuppressants. “These treatments lack strong evidence from clinical trials to support their efficacy, are often poorly tolerated, and can be associated with considerable long-term toxicities,” Dr. Howard and colleagues wrote in their report, which was published in JAMA Neurology.

A total of 44 adult patients with gMG were randomized to receive daily zilucoplan 0.1 mg/kg, 0.3 mg/kg, or placebo for 12 weeks in this 25-center North American study. All patients had acetylcholine receptor autoantibody–positive disease and a Quantitative Myasthenia Gravis (QMG) score of 12 or higher. The QMG score ranges from 0, indicating no muscle weakness, to 39, or severe weakness.

Per the study protocol, patients had to keep taking their current gMG medication without changing the dose.

Change in QMG score from baseline to 12 weeks, the primary efficacy endpoint of the study, showed a significant and clinically meaningful difference favoring zilucoplan 0.3 mg/kg over placebo, according to the investigators.

The mean change was –6.0 points for zilucoplan 0.3 mg/kg and –3.2 for placebo (P = .05), according to their report, which indicated a rapid onset of action apparent 1 week after starting treatment.

Zilucoplan 0.1 mg/kg also yielded a significant and clinically meaningful improvement versus placebo, but its magnitude was smaller and took 4 weeks to become apparent.

Treatment with zilucoplan also significantly improved MG Activities of Daily Living scores versus placebo, a key secondary endpoint of the trial, according to the researchers.

Treatment-emergent adverse events, which included local injection-site reactions, were mild and judged to be unrelated to the study treatment, according to the report.

Ra Pharmaceuticals funded the study. Dr. Howard reported disclosures related to Ra Pharmaceuticals, Alexion Pharmaceuticals, argenx, Viela Bio, and others.

SOURCE: Howard Jr JF et al. JAMA Neurol. 2020 Feb 17. doi: 10.1001/jamaneurol.2019.5125.

The complement C5 inhibitor zilucoplan significantly improved muscle weakness and daily functioning in patients with moderate to severe generalized myasthenia gravis (gMG), according to investigators who conducted a phase 2, randomized, placebo-controlled study of the agent.

The clinical effect of the self-administered macrocyclic peptide inhibitor was “similar,” the investigators wrote, to what was seen in studies of the intravenously administered complement inhibitor eculizumab, which is approved by the Food and Drug Administration for treatment of gMG.

While eculizumab studies were restricted to patients with refractory gMG, the investigators wrote that their study of zilucoplan included a broader population, including patients who had not failed prior therapies, who were earlier in their disease course, and who had a history of thymoma.

“This observation is important because in gMG, disease severity frequently peaks within the first few years after diagnosis, before all treatment options have been exhausted, and before patients may be formally declared treatment refractory,” wrote James F. Howard Jr, MD, of the University of North Carolina in Chapel Hill, and coauthors.

Complement inhibition is a “targeted approach” that addresses the primary mechanism of tissue damage in gMG, the investigators wrote.

That stands in contrast to conventional gMG treatments including pyridostigmine, corticosteroids, and other immunosuppressants. “These treatments lack strong evidence from clinical trials to support their efficacy, are often poorly tolerated, and can be associated with considerable long-term toxicities,” Dr. Howard and colleagues wrote in their report, which was published in JAMA Neurology.

A total of 44 adult patients with gMG were randomized to receive daily zilucoplan 0.1 mg/kg, 0.3 mg/kg, or placebo for 12 weeks in this 25-center North American study. All patients had acetylcholine receptor autoantibody–positive disease and a Quantitative Myasthenia Gravis (QMG) score of 12 or higher. The QMG score ranges from 0, indicating no muscle weakness, to 39, or severe weakness.

Per the study protocol, patients had to keep taking their current gMG medication without changing the dose.

Change in QMG score from baseline to 12 weeks, the primary efficacy endpoint of the study, showed a significant and clinically meaningful difference favoring zilucoplan 0.3 mg/kg over placebo, according to the investigators.

The mean change was –6.0 points for zilucoplan 0.3 mg/kg and –3.2 for placebo (P = .05), according to their report, which indicated a rapid onset of action apparent 1 week after starting treatment.

Zilucoplan 0.1 mg/kg also yielded a significant and clinically meaningful improvement versus placebo, but its magnitude was smaller and took 4 weeks to become apparent.

Treatment with zilucoplan also significantly improved MG Activities of Daily Living scores versus placebo, a key secondary endpoint of the trial, according to the researchers.

Treatment-emergent adverse events, which included local injection-site reactions, were mild and judged to be unrelated to the study treatment, according to the report.

Ra Pharmaceuticals funded the study. Dr. Howard reported disclosures related to Ra Pharmaceuticals, Alexion Pharmaceuticals, argenx, Viela Bio, and others.

SOURCE: Howard Jr JF et al. JAMA Neurol. 2020 Feb 17. doi: 10.1001/jamaneurol.2019.5125.

Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

*This article was updated 2/19/2020.

Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

*This article was updated 2/19/2020.

Kobe Bryant knew me. Not personally, of course. I never received an autograph or shook his hand. But once in a while if I was up early enough, I’d run into Kobe at the gym in Newport Beach where he and I both worked out. As he did for all his fans at the gym, he’d make eye contact with me and nod hello. He was always focused on his workout – working with a trainer, never with headphones on. In person, he appeared enormous. Unlike most retired professional athletes, he still was in great shape. No doubt he could have suited up in purple and gold, and played against the Clippers that night if needed.

Featureflash Photo Agency

Being from New England, I never was a Laker fan. But at Kobe’s peak around 2000, I found him inspiring. I recall watching him play right around the time I was studying for my U.S. medical licensing exams. I thought, if Kobe can head to the gym after midnight and take a 1,000 shots to prepare for a game, then I could set my alarm for 4 a.m. and take a few dozen more questions from my First Aid books. Head down, “Kryptonite” cranked on my iPod, I wasn’t going to let anyone in that test room outwork me. Neither did he. I put in the time and, like Kobe in the 2002 conference finals against Sacramento, I crushed it.*

When we moved to California, I followed Kobe and the Lakers until he retired. To be clear, I didn’t aspire to be like him, firstly because I’m slightly shorter than Michael Bloomberg, but also because although accomplished, Kobe made some poor choices at times. Indeed, it seems he might have been kinder and more considerate when he was at the top. But in his retirement he looked to be toiling to make reparations, refocusing his prodigious energy and talent for the benefit of others rather than for just for scoring 81 points. His Rolls Royce was there before mine at the gym, and I was there early. He was still getting up early and now preparing to be a great venture capitalist, podcaster, author, and father to his girls.

Watching him carry kettle bells across the floor one morning, I wondered, do people like Kobe Bryant look to others for inspiration? Or are they are born with an endless supply of it? For me, I seemed to push harder and faster when watching idols pass by. Whether it was Kobe or Clayton Christensen (author of “The Innovator’s Dilemma”), Joe Jorizzo, or Barack Obama, I found I could do just a bit more if I had them in mind.

On game days, Kobe spoke of arriving at the arena early, long before anyone. He would use the silent, solo time to reflect on what he needed to do perform that night. I tried this last week, arriving at our clinic early, before any patients or staff. I turned the lights on and took a few minutes to think about what we needed to accomplish that day. I previewed patients on my schedule, searched Up to Date for the latest recommendations on a difficult case. I didn’t know Kobe, but I felt like I did.

CC0 1.0 Universal Public Domain Dedication

When I received the text that Kobe Bryant had died, I was actually working on this column. So I decided to change the topic to write about people who inspire me, ironically inspired by him again. May he rest in peace.
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

*This article was updated 2/19/2020.

Private equity firms are increasingly acquiring physician practices across a range of specialties, a recent analysis shows.

Lead author Jane M. Zhu, MD, of Oregon Health & Science University, Portland, and colleagues examined physician group practice acquisitions by private equity firms using the Irving Levin Associates Health Care M&A data set, which includes manually collected and verified transactional information on health care mergers and acquisitions. Investigators linked acquisitions to the SK&A data set, a commercial data set of verified physicians and practice-level characteristics of U.S. office-based practices.

Of about 18,000 unique group medical practices, private equity firms acquired 355 physician practice acquisitions from 2013 to 2016, a trend that rose from 59 practices in 2013 to 136 practices in 2016, Dr. Zhu and colleagues reported on Feb. 18 , 2020, in a research letter published in JAMA.

Acquired practices had a mean of four sites, 16 physicians in each practice, and 6 physicians affiliated with each site, the data found. Overall, 81% of these medical practices reported accepting new patients, 83% accepted Medicare, and 60% accepted Medicaid. The majority of acquired practices were in the South (44%).

Anesthesiology (19%) and multispecialty (19%) were the most commonly represented medical groups in the acquisitions, followed by emergency medicine (12%), family practice (11%), and dermatology (10%). In addition, from 2015 to 2016, the number of acquired cardiology, ophthalmology, radiology, and ob.gyn. practices increased. Within acquired practices, anesthesiologists represented the majority of all physicians, followed by emergency medicine specialists, family physicians, and dermatologists.

Dr. Zhu and colleagues cited a key limitation: Because the data are based on transactions that have been publicly announced, the acquisition of smaller practices might have been underestimated.

Still, the findings demonstrate that private equity acquisitions of physician medical groups are accelerating across multiple specialties, Dr. Zhu said in an interview.

“From our data, acquired medical groups seem to have relatively large footprints with multiple office sites and multiple physicians, which mirrors a typical investment strategy for these firms,” she said.

Dr. Zhu said that more research is needed about how these purchases affect practice patterns, delivery of care, and clinician behavior. Private equity firms expect greater than 20% annual returns, and such financial incentives may conflict with the need for longer-term investments in practice stability, physician recruitment, quality, and safety, according to the study.

“In theory, there may be greater efficiencies introduced from private equity investment – for example, through administrative and billing efficiencies, reorganizing practice structures, or strengthening technology supports,” Dr. Zhu said. “But because of private equity firms’ emphasis on return on investment, there may be unintended consequences of these purchases on practice stability and patient care. We don’t yet know what these effects will be, and we need robust, longitudinal data to investigate this question.”

Dr. Zhu and colleagues reported that they had no disclosures.

SOURCE: Zhu JM et al. JAMA. 2020 Feb 18;323(17):663-5.

Private equity firms are increasingly acquiring physician practices across a range of specialties, a recent analysis shows.

Lead author Jane M. Zhu, MD, of Oregon Health & Science University, Portland, and colleagues examined physician group practice acquisitions by private equity firms using the Irving Levin Associates Health Care M&A data set, which includes manually collected and verified transactional information on health care mergers and acquisitions. Investigators linked acquisitions to the SK&A data set, a commercial data set of verified physicians and practice-level characteristics of U.S. office-based practices.

Of about 18,000 unique group medical practices, private equity firms acquired 355 physician practice acquisitions from 2013 to 2016, a trend that rose from 59 practices in 2013 to 136 practices in 2016, Dr. Zhu and colleagues reported on Feb. 18 , 2020, in a research letter published in JAMA.

Acquired practices had a mean of four sites, 16 physicians in each practice, and 6 physicians affiliated with each site, the data found. Overall, 81% of these medical practices reported accepting new patients, 83% accepted Medicare, and 60% accepted Medicaid. The majority of acquired practices were in the South (44%).

Anesthesiology (19%) and multispecialty (19%) were the most commonly represented medical groups in the acquisitions, followed by emergency medicine (12%), family practice (11%), and dermatology (10%). In addition, from 2015 to 2016, the number of acquired cardiology, ophthalmology, radiology, and ob.gyn. practices increased. Within acquired practices, anesthesiologists represented the majority of all physicians, followed by emergency medicine specialists, family physicians, and dermatologists.

Dr. Zhu and colleagues cited a key limitation: Because the data are based on transactions that have been publicly announced, the acquisition of smaller practices might have been underestimated.

Still, the findings demonstrate that private equity acquisitions of physician medical groups are accelerating across multiple specialties, Dr. Zhu said in an interview.

“From our data, acquired medical groups seem to have relatively large footprints with multiple office sites and multiple physicians, which mirrors a typical investment strategy for these firms,” she said.

Dr. Zhu said that more research is needed about how these purchases affect practice patterns, delivery of care, and clinician behavior. Private equity firms expect greater than 20% annual returns, and such financial incentives may conflict with the need for longer-term investments in practice stability, physician recruitment, quality, and safety, according to the study.

“In theory, there may be greater efficiencies introduced from private equity investment – for example, through administrative and billing efficiencies, reorganizing practice structures, or strengthening technology supports,” Dr. Zhu said. “But because of private equity firms’ emphasis on return on investment, there may be unintended consequences of these purchases on practice stability and patient care. We don’t yet know what these effects will be, and we need robust, longitudinal data to investigate this question.”

Dr. Zhu and colleagues reported that they had no disclosures.

SOURCE: Zhu JM et al. JAMA. 2020 Feb 18;323(17):663-5.

Private equity firms are increasingly acquiring physician practices across a range of specialties, a recent analysis shows.

Lead author Jane M. Zhu, MD, of Oregon Health & Science University, Portland, and colleagues examined physician group practice acquisitions by private equity firms using the Irving Levin Associates Health Care M&A data set, which includes manually collected and verified transactional information on health care mergers and acquisitions. Investigators linked acquisitions to the SK&A data set, a commercial data set of verified physicians and practice-level characteristics of U.S. office-based practices.

Of about 18,000 unique group medical practices, private equity firms acquired 355 physician practice acquisitions from 2013 to 2016, a trend that rose from 59 practices in 2013 to 136 practices in 2016, Dr. Zhu and colleagues reported on Feb. 18 , 2020, in a research letter published in JAMA.

Acquired practices had a mean of four sites, 16 physicians in each practice, and 6 physicians affiliated with each site, the data found. Overall, 81% of these medical practices reported accepting new patients, 83% accepted Medicare, and 60% accepted Medicaid. The majority of acquired practices were in the South (44%).

Anesthesiology (19%) and multispecialty (19%) were the most commonly represented medical groups in the acquisitions, followed by emergency medicine (12%), family practice (11%), and dermatology (10%). In addition, from 2015 to 2016, the number of acquired cardiology, ophthalmology, radiology, and ob.gyn. practices increased. Within acquired practices, anesthesiologists represented the majority of all physicians, followed by emergency medicine specialists, family physicians, and dermatologists.

Dr. Zhu and colleagues cited a key limitation: Because the data are based on transactions that have been publicly announced, the acquisition of smaller practices might have been underestimated.

Still, the findings demonstrate that private equity acquisitions of physician medical groups are accelerating across multiple specialties, Dr. Zhu said in an interview.

“From our data, acquired medical groups seem to have relatively large footprints with multiple office sites and multiple physicians, which mirrors a typical investment strategy for these firms,” she said.

Dr. Zhu said that more research is needed about how these purchases affect practice patterns, delivery of care, and clinician behavior. Private equity firms expect greater than 20% annual returns, and such financial incentives may conflict with the need for longer-term investments in practice stability, physician recruitment, quality, and safety, according to the study.

“In theory, there may be greater efficiencies introduced from private equity investment – for example, through administrative and billing efficiencies, reorganizing practice structures, or strengthening technology supports,” Dr. Zhu said. “But because of private equity firms’ emphasis on return on investment, there may be unintended consequences of these purchases on practice stability and patient care. We don’t yet know what these effects will be, and we need robust, longitudinal data to investigate this question.”

Dr. Zhu and colleagues reported that they had no disclosures.

SOURCE: Zhu JM et al. JAMA. 2020 Feb 18;323(17):663-5.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

sworcester@mdedge.com

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

sworcester@mdedge.com

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

The risk of hip fracture was higher among patients treated with tramadol for chronic noncancer pain than among those treated with other commonly used NSAIDs in a large population-based cohort in the United Kingdom.

iStock/Thinkstock

The incidence of hip fracture over a 12-month period among 293,912 propensity score-matched tramadol and codeine recipients in The Health Improvement Network (THIN) database during 2000-2017 was 3.7 vs. 2.9 per 1,000 person-years, respectively (hazard ratio for hip fracture, 1.28), Jie Wei, PhD, of Xiangya Hospital, Central South University, Changsha, China, and colleagues reported in the Journal of Bone and Mineral Research.

Hip fracture incidence per 1,000 person-years was also higher in propensity score–matched cohorts of patients receiving tramadol vs. naproxen (2.9 vs. 1.7; HR, 1.69), ibuprofen (3.4 vs. 2.0; HR, 1.65), celecoxib (3.4 vs. 1.8; HR, 1.85), or etoricoxib (2.9 vs. 1.5; HR, 1.96), the investigators found.

Tramadol is considered a weak opioid and is commonly used for the treatment of pain based on a lower perceived risk of serious cardiovascular and gastrointestinal effects versus NSAIDs, and of addiction and respiratory depression versus traditional opioids, they explained. Several professional organizations also have “strongly or conditionally recommended tramadol” as a first- or second-line treatment for conditions such as osteoarthritis, fibromyalgia, and chronic low back pain.

The potential mechanisms for the association between tramadol and hip fracture require further study, but “[c]onsidering the significant impact of hip fracture on morbidity, mortality, and health care costs, our results point to the need to consider tramadol’s associated risk of fracture in clinical practice and treatment guidelines,” they concluded.

This study was supported by the National Institutes of Health, the National Natural Science Foundation of China, and the Postdoctoral Science Foundation of Central South University. The authors reported having no conflicts of interest.

sworcester@mdedge.com

SOURCE: Wei J et al. J Bone Miner Res. 2019 Feb 5. doi: 10.1002/jbmr.3935.

No antiepileptic drug (AED) is independently associated with cognitive dysfunction, according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.

Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
 

Researchers analyzed patients admitted for video EEG monitoring

For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.

The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.

All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.

Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
 

Almost half of patients were prescribed polypharmacy

The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).

Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.

Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
 

Future studies could address particular cognitive domains

Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.

Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.

Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”

The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”

Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”

The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.

egreb@mdedge.com

SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.

No antiepileptic drug (AED) is independently associated with cognitive dysfunction, according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.

Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
 

Researchers analyzed patients admitted for video EEG monitoring

For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.

The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.

All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.

Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
 

Almost half of patients were prescribed polypharmacy

The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).

Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.

Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
 

Future studies could address particular cognitive domains

Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.

Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.

Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”

The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”

Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”

The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.

egreb@mdedge.com

SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.

No antiepileptic drug (AED) is independently associated with cognitive dysfunction, according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.

Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
 

Researchers analyzed patients admitted for video EEG monitoring

For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.

The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.

All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.

Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
 

Almost half of patients were prescribed polypharmacy

The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).

Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.

Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
 

Future studies could address particular cognitive domains

Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.

Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.

Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”

The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”

Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”

The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.

egreb@mdedge.com

SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.