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.

LAHAINA, HAWAII – The list of nontraditional uses for botulinum toxin type A includes facial flushing, menopausal hot flashes, and androgenetic alopecia, Mark Rubin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

There are data to support these uses, and there are data associating botulinum toxin treatment with improvement in depression, which suggest the effect may not be necessarily be related to improvement in appearance, said Dr. Rubin, who is in private practice in Beverly Hills, Calif., and is associate professor of dermatology at the University of California, San Diego.

Facial flushing: Very few people use botulinum toxin for facial flushing, but Dr. Rubin, who is among those who do not, described the data as “impressive.” Several trials, he noted, have found that very small doses can significantly reduce the amount of facial erythema, including an average 45% reduction after 60 days in one trial of 24 women (Acta Med Iran. 2016 Jul;54[7]:454-7).

In another study of 25 patients with facial erythema related to rosacea who were treated with 14-45 units intradermally to the nasal tip, bridge, and alae, there were statistically significant improvements in erythema 1, 2, and 3 months after treatment among the 15 with complete data (Dermatol Surg. 2015 Jan;41 Suppl 1:S9-16).

“If you’re using very small doses and they’re intradermal, there really is minimal risk you’re going to have a problem by inadvertently affecting musculature” in these patients, Dr. Rubin commented.

In another study of 9 patients with rosacea, treatment with incobotulinumtoxinA was associated with a significant reduction in erythema, papules, pustules, and telangiectasias, up to 15 weeks, compared with saline. The treatment patients also experienced less burning and stinging that did those who received saline (J Drugs Dermatol. 2017 Jun 1;16[6]:549-54.)

Menopausal hot flashes: Dr. Rubin described one study of 60 patients with severe hot flashes that compared saline with botulinum toxin, injected in 40 sites (2 units per site), including the neck, hairline, scalp, and chest. At 60 days’ follow-up, those treated with botulinum toxin had a significant reduction in sweating and in the number and severity of hot flashes; these women also had improved mood in terms of depression and irritability (Dermatol Surg. 2011 Nov;37[11]:1579-83).

Androgenetic alopecia: In a 60-week study of 50 men with androgenetic alopecia (Hamilton ratings of II-IV), 150 units of botulinum toxin A was injected into the scalp muscles (temporalis, frontalis, periauricular, and occipital), and repeated 6 months later (Plast Reconstr Surg. 2010 Nov;126[5]:246e-8e). Among the 40 patients who completed the trial, 75% had a response, and from baseline to 48 weeks, there was an 18% increase in mean hair counts in a 2 cm area, and a“profound” 39% reduction in hair loss (as measured by hair counts on the pillow in the morning), Dr. Rubin noted.

“Presumably, this is because if you’re relaxing the scalp muscles you’re getting increased blood flow into the scalp,” including increased oxygenation, which decreases the conversion of testosterone to dihydrotestosterone and increases the conversion of testosterone to estradiol, he said.

In another study, 8 of 10 patients with androgenic alopecia has “good to excellent” results 24 weeks after botulinum toxin injections with 5 units per site at 30 sites. Referring to the increasing popularity of platelet-rich plasma (PRP) injections for male pattern alopecia, Dr. Rubin said that in his opinion “PRP certainly doesn’t do any better” than botulinum toxin for male pattern alopecia and is a much more involved injection, “so this is definitely something worth considering if you have more people coming into your practice thinking about injections for male pattern alopecia.”

Pore size and sebum production: A 2019 review of published studies of botulinum toxin A looking at the effect on sebum and pore size, Dr. Rubin said, found that most studies “suggest it does actually reduce pore size and sebum production” (J Cosmet Dermatol. 2019 Apr;18[2]:451-7).

This can be considered an option for those patients concerned about pore size, who are not satisfied with results of retinoid or laser treatment, he commented. This approach may not have an effect in all patients, so he advised first treating a small trial area, and photographing patients to record their level of improvement. “It’s rarely profound, but it’s additive, it’s one more thing you can do.”

Depression: These data include a study of 30 patients with major depression, half who received one onabotulinumtoxinA injection in the glabellar area as adjunctive treatment of depression. After 6 weeks, those who were treated had an average of 47% reduction in depression scores on the Hamilton Depression Rating Scale, compared with an average 9% reduction among those on placebo (J Psychiatr Res. 2012 May;46[5]:574-81). Two recent studies have had similar results, according to Dr. Rubin.

Results of another study, he said, raise the question of whether patients are less depressed because they are pleased with the cosmetic effects or if there is another explanation (J Am Acad Dermatol. 2016 Jan;74[1]:171-3.e1). The study, which included 59 patients with depression treated in the glabellar areas with botulinum toxin injections, found no association between severity of the furrows and degree of depression or between the degree of furrow correction and degree of relief from depression after treatment. “So the patients who had the most improvement were not necessarily the ones who were the least depressed afterwards,” he said.

These data imply that something else may be occurring that is not necessarily muscle related, he said.

Dr. Rubin said he had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

emechcatie@mdedge.com

LAHAINA, HAWAII – The list of nontraditional uses for botulinum toxin type A includes facial flushing, menopausal hot flashes, and androgenetic alopecia, Mark Rubin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

There are data to support these uses, and there are data associating botulinum toxin treatment with improvement in depression, which suggest the effect may not be necessarily be related to improvement in appearance, said Dr. Rubin, who is in private practice in Beverly Hills, Calif., and is associate professor of dermatology at the University of California, San Diego.

Facial flushing: Very few people use botulinum toxin for facial flushing, but Dr. Rubin, who is among those who do not, described the data as “impressive.” Several trials, he noted, have found that very small doses can significantly reduce the amount of facial erythema, including an average 45% reduction after 60 days in one trial of 24 women (Acta Med Iran. 2016 Jul;54[7]:454-7).

In another study of 25 patients with facial erythema related to rosacea who were treated with 14-45 units intradermally to the nasal tip, bridge, and alae, there were statistically significant improvements in erythema 1, 2, and 3 months after treatment among the 15 with complete data (Dermatol Surg. 2015 Jan;41 Suppl 1:S9-16).

“If you’re using very small doses and they’re intradermal, there really is minimal risk you’re going to have a problem by inadvertently affecting musculature” in these patients, Dr. Rubin commented.

In another study of 9 patients with rosacea, treatment with incobotulinumtoxinA was associated with a significant reduction in erythema, papules, pustules, and telangiectasias, up to 15 weeks, compared with saline. The treatment patients also experienced less burning and stinging that did those who received saline (J Drugs Dermatol. 2017 Jun 1;16[6]:549-54.)

Menopausal hot flashes: Dr. Rubin described one study of 60 patients with severe hot flashes that compared saline with botulinum toxin, injected in 40 sites (2 units per site), including the neck, hairline, scalp, and chest. At 60 days’ follow-up, those treated with botulinum toxin had a significant reduction in sweating and in the number and severity of hot flashes; these women also had improved mood in terms of depression and irritability (Dermatol Surg. 2011 Nov;37[11]:1579-83).

Androgenetic alopecia: In a 60-week study of 50 men with androgenetic alopecia (Hamilton ratings of II-IV), 150 units of botulinum toxin A was injected into the scalp muscles (temporalis, frontalis, periauricular, and occipital), and repeated 6 months later (Plast Reconstr Surg. 2010 Nov;126[5]:246e-8e). Among the 40 patients who completed the trial, 75% had a response, and from baseline to 48 weeks, there was an 18% increase in mean hair counts in a 2 cm area, and a“profound” 39% reduction in hair loss (as measured by hair counts on the pillow in the morning), Dr. Rubin noted.

“Presumably, this is because if you’re relaxing the scalp muscles you’re getting increased blood flow into the scalp,” including increased oxygenation, which decreases the conversion of testosterone to dihydrotestosterone and increases the conversion of testosterone to estradiol, he said.

In another study, 8 of 10 patients with androgenic alopecia has “good to excellent” results 24 weeks after botulinum toxin injections with 5 units per site at 30 sites. Referring to the increasing popularity of platelet-rich plasma (PRP) injections for male pattern alopecia, Dr. Rubin said that in his opinion “PRP certainly doesn’t do any better” than botulinum toxin for male pattern alopecia and is a much more involved injection, “so this is definitely something worth considering if you have more people coming into your practice thinking about injections for male pattern alopecia.”

Pore size and sebum production: A 2019 review of published studies of botulinum toxin A looking at the effect on sebum and pore size, Dr. Rubin said, found that most studies “suggest it does actually reduce pore size and sebum production” (J Cosmet Dermatol. 2019 Apr;18[2]:451-7).

This can be considered an option for those patients concerned about pore size, who are not satisfied with results of retinoid or laser treatment, he commented. This approach may not have an effect in all patients, so he advised first treating a small trial area, and photographing patients to record their level of improvement. “It’s rarely profound, but it’s additive, it’s one more thing you can do.”

Depression: These data include a study of 30 patients with major depression, half who received one onabotulinumtoxinA injection in the glabellar area as adjunctive treatment of depression. After 6 weeks, those who were treated had an average of 47% reduction in depression scores on the Hamilton Depression Rating Scale, compared with an average 9% reduction among those on placebo (J Psychiatr Res. 2012 May;46[5]:574-81). Two recent studies have had similar results, according to Dr. Rubin.

Results of another study, he said, raise the question of whether patients are less depressed because they are pleased with the cosmetic effects or if there is another explanation (J Am Acad Dermatol. 2016 Jan;74[1]:171-3.e1). The study, which included 59 patients with depression treated in the glabellar areas with botulinum toxin injections, found no association between severity of the furrows and degree of depression or between the degree of furrow correction and degree of relief from depression after treatment. “So the patients who had the most improvement were not necessarily the ones who were the least depressed afterwards,” he said.

These data imply that something else may be occurring that is not necessarily muscle related, he said.

Dr. Rubin said he had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

emechcatie@mdedge.com

LAHAINA, HAWAII – The list of nontraditional uses for botulinum toxin type A includes facial flushing, menopausal hot flashes, and androgenetic alopecia, Mark Rubin, MD, said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

There are data to support these uses, and there are data associating botulinum toxin treatment with improvement in depression, which suggest the effect may not be necessarily be related to improvement in appearance, said Dr. Rubin, who is in private practice in Beverly Hills, Calif., and is associate professor of dermatology at the University of California, San Diego.

Facial flushing: Very few people use botulinum toxin for facial flushing, but Dr. Rubin, who is among those who do not, described the data as “impressive.” Several trials, he noted, have found that very small doses can significantly reduce the amount of facial erythema, including an average 45% reduction after 60 days in one trial of 24 women (Acta Med Iran. 2016 Jul;54[7]:454-7).

In another study of 25 patients with facial erythema related to rosacea who were treated with 14-45 units intradermally to the nasal tip, bridge, and alae, there were statistically significant improvements in erythema 1, 2, and 3 months after treatment among the 15 with complete data (Dermatol Surg. 2015 Jan;41 Suppl 1:S9-16).

“If you’re using very small doses and they’re intradermal, there really is minimal risk you’re going to have a problem by inadvertently affecting musculature” in these patients, Dr. Rubin commented.

In another study of 9 patients with rosacea, treatment with incobotulinumtoxinA was associated with a significant reduction in erythema, papules, pustules, and telangiectasias, up to 15 weeks, compared with saline. The treatment patients also experienced less burning and stinging that did those who received saline (J Drugs Dermatol. 2017 Jun 1;16[6]:549-54.)

Menopausal hot flashes: Dr. Rubin described one study of 60 patients with severe hot flashes that compared saline with botulinum toxin, injected in 40 sites (2 units per site), including the neck, hairline, scalp, and chest. At 60 days’ follow-up, those treated with botulinum toxin had a significant reduction in sweating and in the number and severity of hot flashes; these women also had improved mood in terms of depression and irritability (Dermatol Surg. 2011 Nov;37[11]:1579-83).

Androgenetic alopecia: In a 60-week study of 50 men with androgenetic alopecia (Hamilton ratings of II-IV), 150 units of botulinum toxin A was injected into the scalp muscles (temporalis, frontalis, periauricular, and occipital), and repeated 6 months later (Plast Reconstr Surg. 2010 Nov;126[5]:246e-8e). Among the 40 patients who completed the trial, 75% had a response, and from baseline to 48 weeks, there was an 18% increase in mean hair counts in a 2 cm area, and a“profound” 39% reduction in hair loss (as measured by hair counts on the pillow in the morning), Dr. Rubin noted.

“Presumably, this is because if you’re relaxing the scalp muscles you’re getting increased blood flow into the scalp,” including increased oxygenation, which decreases the conversion of testosterone to dihydrotestosterone and increases the conversion of testosterone to estradiol, he said.

In another study, 8 of 10 patients with androgenic alopecia has “good to excellent” results 24 weeks after botulinum toxin injections with 5 units per site at 30 sites. Referring to the increasing popularity of platelet-rich plasma (PRP) injections for male pattern alopecia, Dr. Rubin said that in his opinion “PRP certainly doesn’t do any better” than botulinum toxin for male pattern alopecia and is a much more involved injection, “so this is definitely something worth considering if you have more people coming into your practice thinking about injections for male pattern alopecia.”

Pore size and sebum production: A 2019 review of published studies of botulinum toxin A looking at the effect on sebum and pore size, Dr. Rubin said, found that most studies “suggest it does actually reduce pore size and sebum production” (J Cosmet Dermatol. 2019 Apr;18[2]:451-7).

This can be considered an option for those patients concerned about pore size, who are not satisfied with results of retinoid or laser treatment, he commented. This approach may not have an effect in all patients, so he advised first treating a small trial area, and photographing patients to record their level of improvement. “It’s rarely profound, but it’s additive, it’s one more thing you can do.”

Depression: These data include a study of 30 patients with major depression, half who received one onabotulinumtoxinA injection in the glabellar area as adjunctive treatment of depression. After 6 weeks, those who were treated had an average of 47% reduction in depression scores on the Hamilton Depression Rating Scale, compared with an average 9% reduction among those on placebo (J Psychiatr Res. 2012 May;46[5]:574-81). Two recent studies have had similar results, according to Dr. Rubin.

Results of another study, he said, raise the question of whether patients are less depressed because they are pleased with the cosmetic effects or if there is another explanation (J Am Acad Dermatol. 2016 Jan;74[1]:171-3.e1). The study, which included 59 patients with depression treated in the glabellar areas with botulinum toxin injections, found no association between severity of the furrows and degree of depression or between the degree of furrow correction and degree of relief from depression after treatment. “So the patients who had the most improvement were not necessarily the ones who were the least depressed afterwards,” he said.

These data imply that something else may be occurring that is not necessarily muscle related, he said.

Dr. Rubin said he had no relevant disclosures. SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

emechcatie@mdedge.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.

NATIONAL HARBOR, MD. – Cardiac electrophysiologists have reported using pulsed field ablation, a new power source for catheter ablation of atrial fibrillation, on fewer than 150 patients worldwide in initial clinical studies, but its performance so far and the promise it carries for substantially improving the safety and efficacy of catheter ablation has convinced many experts that it represents the future for this intervention.

“I’m very excited about PFA [pulsed field ablation]. It may make everything else obsolete,” Andrea Natale, MD, said at the annual International AF Symposium. “We need to see more efficacy data, but just for safety alone there is no reason to use anything else,” commented Dr. Natale, executive medical director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin,Tex.

“The main issue is safety, and if PFA lives up to its promise, then [using it preferentially] is not a difficult decision,” commented Francis E. Marchlinski, MD, professor of medicine and director of electrophysiology at the University of Pennsylvania.

The pulsed field ablation studies have been sponsored by Farapulse, the company developing this device, which in May 2019 received breakthrough designation for priority review from the Food and Drug Administration.

Dr. Reddy and Dr. Jaïs are both consultants to and shareholders in Farapulse. Dr. Natale has received honoraria from or has been a consultant to Biotronik, Janssen, Medtronic, and St. Jude. Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biotronik, and Medtronic. Dr. Mansour has been a consultant for Abbott and Medtronic, has an equity interest or stock options in NewPace and EPD Solutions, and has received research grants from Abbott, Boehringer Ingelheim, Pfizer, and Sentre Heart. In addition, all sources have received consulting fees, honoraria, and/or research grants from Biosense Webster and Boston Scientific.

mzoler@mdedge.com

NATIONAL HARBOR, MD. – Cardiac electrophysiologists have reported using pulsed field ablation, a new power source for catheter ablation of atrial fibrillation, on fewer than 150 patients worldwide in initial clinical studies, but its performance so far and the promise it carries for substantially improving the safety and efficacy of catheter ablation has convinced many experts that it represents the future for this intervention.

“I’m very excited about PFA [pulsed field ablation]. It may make everything else obsolete,” Andrea Natale, MD, said at the annual International AF Symposium. “We need to see more efficacy data, but just for safety alone there is no reason to use anything else,” commented Dr. Natale, executive medical director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin,Tex.

“The main issue is safety, and if PFA lives up to its promise, then [using it preferentially] is not a difficult decision,” commented Francis E. Marchlinski, MD, professor of medicine and director of electrophysiology at the University of Pennsylvania.

The pulsed field ablation studies have been sponsored by Farapulse, the company developing this device, which in May 2019 received breakthrough designation for priority review from the Food and Drug Administration.

Dr. Reddy and Dr. Jaïs are both consultants to and shareholders in Farapulse. Dr. Natale has received honoraria from or has been a consultant to Biotronik, Janssen, Medtronic, and St. Jude. Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biotronik, and Medtronic. Dr. Mansour has been a consultant for Abbott and Medtronic, has an equity interest or stock options in NewPace and EPD Solutions, and has received research grants from Abbott, Boehringer Ingelheim, Pfizer, and Sentre Heart. In addition, all sources have received consulting fees, honoraria, and/or research grants from Biosense Webster and Boston Scientific.

mzoler@mdedge.com

NATIONAL HARBOR, MD. – Cardiac electrophysiologists have reported using pulsed field ablation, a new power source for catheter ablation of atrial fibrillation, on fewer than 150 patients worldwide in initial clinical studies, but its performance so far and the promise it carries for substantially improving the safety and efficacy of catheter ablation has convinced many experts that it represents the future for this intervention.

“I’m very excited about PFA [pulsed field ablation]. It may make everything else obsolete,” Andrea Natale, MD, said at the annual International AF Symposium. “We need to see more efficacy data, but just for safety alone there is no reason to use anything else,” commented Dr. Natale, executive medical director of the Texas Cardiac Arrhythmia Institute at St. David’s Medical Center in Austin,Tex.

“The main issue is safety, and if PFA lives up to its promise, then [using it preferentially] is not a difficult decision,” commented Francis E. Marchlinski, MD, professor of medicine and director of electrophysiology at the University of Pennsylvania.

The pulsed field ablation studies have been sponsored by Farapulse, the company developing this device, which in May 2019 received breakthrough designation for priority review from the Food and Drug Administration.

Dr. Reddy and Dr. Jaïs are both consultants to and shareholders in Farapulse. Dr. Natale has received honoraria from or has been a consultant to Biotronik, Janssen, Medtronic, and St. Jude. Dr. Marchlinski has been a consultant to or has received honoraria from Abbott EP/St. Jude, Biotronik, and Medtronic. Dr. Mansour has been a consultant for Abbott and Medtronic, has an equity interest or stock options in NewPace and EPD Solutions, and has received research grants from Abbott, Boehringer Ingelheim, Pfizer, and Sentre Heart. In addition, all sources have received consulting fees, honoraria, and/or research grants from Biosense Webster and Boston Scientific.

mzoler@mdedge.com

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

AUSTIN, TEX. – A program of frequent monitoring in Crohn’s disease and ulcerative colitis that includes fecal calprotectin (FC) and C-reactive protein (CRP) testing may be cost effective to significantly reduce disease recurrence and hospitalization rates, according to a review of published studies presented at the annual congress of the Crohn’s & Colitis Foundation and the American Gastroenterological Association.

“Some data show that calprotectin levels rise months before the onset of symptoms, so it’s my practice that every 3-4 months patients should undergo CRP and calprotectin testing, if they’re willing to do so, while they’re on biologic therapy,” Frank I. Scott, MD, MSCE, of the University of Colorado in Aurora, Denver, said in an interview after the presentation.

Regular monitoring of the two levels makes sense as the practice of tight control of IBD symptoms and treating to target has emerged over the past decade, Dr. Scott said. He noted the 2015 Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) guidelines called for using CRP and FC as adjunctive targets only in symptom assessment (Am J Gastroenterol. 2015:110[9]:1324-58). “I argue that we’ve had a growing body of literature that we should be using these tests regularly as well,” he said.

STRIDE calls for endoscopic assessment 6-9 months after therapy change and consideration of cross-sectional imaging if the small bowel is involved, with assessment every 3 months until symptoms improve and then every 6-12 months thereafter.

However, Dr. Scott noted potential drawbacks to these follow-up steps. “They currently focus on clinical symptoms in the short-term follow-up, and we know from looking at our disease activity indices, such as the CDAI [Crohn’s disease activity index] or Harvey-Bradshaw index, that they don’t always perfectly correlate with actual mucosal healing or resolution of inflammation in Crohn’s or [ulcerative colitis],” he said, pointing to a 2014 study that found CDAI had an area under the curve of 0.57, “which is pretty poor correlation” (Gut. 2014;63[1]:88-95).

Whereas a study of 2,499 patients that showed CRP had an area under the curve of 0.72 and FC of 0.89 (Am J Gastroentrol. 2015;110[6]:802-19). “CRP is a really attractive potential noninvasive marker of inflammation,” he said. “It’s relatively inexpensive, it’s widely available, and the cutoff ranges are well defined.”

He noted four potential drawbacks of CRP: the false-positive rate is relatively high; as a marker of systemic inflammation it’s not specific to the GI tract; false negatives have been well described, with up to 15% of patients not registering a response; and levels can depend on disease location. “Those with isolated ileal disease, for instance, may have relatively low CRP elevations when their disease is active,” Dr. Scott said.

Stool-based FC “represents a potentially more attractive option,” Dr. Scott said. Along with an area under the curve superior to CRP, FC has a documented sensitivity and specificity of 88% and 73%, respectively, versus 49% and 92% for CRP. Drawbacks of fecal calprotectin are that it’s specific to the GI tract but not inflammatory bowel disease, it costs more, and insurance coverage is not as universal as it is for CRP, although more carriers are covering the test, he said.

“However, we do know that through clinical trial data that the use of CRP and FC, in addition to clinical symptom monitoring, does appear to improve care,” Dr. Scott said, noting that the CALM trial of tight disease control through the frequent use of biochemical markers of inflammation with anti–tumor necrosis therapy bore this out (Lancet. 2018;390[10114]:2779-89). “This trial was able to demonstrate at 48 weeks that mucosal healing rates were improved in those receiving CRP and FC monitoring, compared to symptom monitoring alone, with higher rates of steroid-free remission at each visit, which persisted over the follow-up time.”

Dr. Scott also cited a post hoc analysis of CALM trial data that validated CRP and FC monitoring to improve steroid-free remission rates and other outcomes (Gut. 2019 Jul 8. doi: 10.1136/gutjnl-2019-318256). That trial reported steroid-free remission rates of 39.3% with clinical management and 59.8% with tight control, a 34% overall difference (P less than .001). “And it was cost effective to incorporate this monitoring at a cost of about $24,300 per quality-adjusted life-year, well below the typically used $50,000 willingness-to-pay threshold when considering new tests,” Dr. Scott said.

Dr. Scott acknowledged that FC testing may pose some inconvenience to patients when collecting their stool samples, but accuracy has improved. “Laboratories are becoming more reliable in terms of what the values are, and the cutoffs are becoming more defined as far as what’s positive and what’s negative, so it’s good way to monitor whether or not patients are at increased risk of a future flare,” he said.

Dr. Scott reported financial relationships with Takeda, Janssen, Merck and PRIME.

SOURCE: Scott FI et al. Crohn’s & Colitis Congress 2020, Session Sp125.

Underlying cardiac disease, airway anomalies, and younger age each independently boosted the risk of severe perioperative respiratory adverse events (PRAE) in children undergoing adenotonsillectomy to treat obstructive sleep apnea, in a review of 374 patients treated at a single Canadian tertiary-referral center.

In contrast, the analysis failed to show independent, significant effects from any assessed polysomnography or oximetry parameters on the rate of postoperative respiratory complications. The utility of preoperative polysomnography or oximetry for risk stratification is questionable for pediatric patients scheduled to adenotonsillectomy to treat obstructive sleep apnea, wrote Sherri L. Katz, MD, of the University of Ottawa, and associates in a recent report published in the Journal of Clinical Sleep Medicine, although they also added that making these assessments may be “unavoidable” because of their need for diagnosing obstructive sleep apnea and determining the need for surgery.

Despite this caveat, “overall our study results highlight the need to better define the complex interaction between comorbidities, age, nocturnal respiratory events, and gas exchange abnormalities in predicting risk for PRAE” after adenotonsillectomy, the researchers wrote. These findings “are consistent with existing clinical care guidelines,” and “cardiac and craniofacial conditions have been associated with risk of postoperative complications in other studies.”

The analysis used data collected from all children aged 0-18 years who underwent polysomnography assessment followed by adenotonsillectomy at one Canadian tertiary-referral center, Children’s Hospital of Eastern Ontario in Ottawa, during 2010-2016. Their median age was just over 6 years, and 39 patients (10%) were younger than 3 years at the time of their surgery. More than three-quarters of the patients, 286, had at least one identified comorbidity, and nearly half had at least two comorbidities. Polysomnography identified sleep-disordered breathing in 344 of the children (92%), and diagnosed obstructive sleep apnea in 256 (68%), including 148 (43% of the full cohort) with a severe apnea-hypopnea index.

Sixty-six of the children (18%) had at least one severe PRAE that required intervention. Specifically these were either oxygen desaturations requiring intervention or need for airway or ventilatory support with interventions such as jaw thrust, oral or nasal airway placement, bag and mask ventilation, or endotracheal intubation.

A multivariate regression analysis of the measured comorbidity, polysomnography, and oximetry parameters, as well as age, identified three factors that independently linked with a statistically significant increase in the rate of severe PRAE: airway anomaly, underlying cardiac disease, and young age. Patients with an airway anomaly had a 219% increased rate of PRAE, compared with those with no anomaly; patients with underlying cardiac disease had a 109% increased rate, compared with those without cardiac disease; and patients aged younger than 3 years had a 310% higher rate of PRAE, compared with the children aged 6 years or older, while children aged 3-5 years had a 121% higher rate of PRAE, compared with older children.

The study received no commercial funding. Dr. Katz has received honoraria for speaking from Biogen that had no relevance to the study.

mzoler@mdedge.com

SOURCE: Katz SL et al. J Clin Sleep Med. 2020 Jan 15;16(1):41-8.

Underlying cardiac disease, airway anomalies, and younger age each independently boosted the risk of severe perioperative respiratory adverse events (PRAE) in children undergoing adenotonsillectomy to treat obstructive sleep apnea, in a review of 374 patients treated at a single Canadian tertiary-referral center.

In contrast, the analysis failed to show independent, significant effects from any assessed polysomnography or oximetry parameters on the rate of postoperative respiratory complications. The utility of preoperative polysomnography or oximetry for risk stratification is questionable for pediatric patients scheduled to adenotonsillectomy to treat obstructive sleep apnea, wrote Sherri L. Katz, MD, of the University of Ottawa, and associates in a recent report published in the Journal of Clinical Sleep Medicine, although they also added that making these assessments may be “unavoidable” because of their need for diagnosing obstructive sleep apnea and determining the need for surgery.

Despite this caveat, “overall our study results highlight the need to better define the complex interaction between comorbidities, age, nocturnal respiratory events, and gas exchange abnormalities in predicting risk for PRAE” after adenotonsillectomy, the researchers wrote. These findings “are consistent with existing clinical care guidelines,” and “cardiac and craniofacial conditions have been associated with risk of postoperative complications in other studies.”

The analysis used data collected from all children aged 0-18 years who underwent polysomnography assessment followed by adenotonsillectomy at one Canadian tertiary-referral center, Children’s Hospital of Eastern Ontario in Ottawa, during 2010-2016. Their median age was just over 6 years, and 39 patients (10%) were younger than 3 years at the time of their surgery. More than three-quarters of the patients, 286, had at least one identified comorbidity, and nearly half had at least two comorbidities. Polysomnography identified sleep-disordered breathing in 344 of the children (92%), and diagnosed obstructive sleep apnea in 256 (68%), including 148 (43% of the full cohort) with a severe apnea-hypopnea index.

Sixty-six of the children (18%) had at least one severe PRAE that required intervention. Specifically these were either oxygen desaturations requiring intervention or need for airway or ventilatory support with interventions such as jaw thrust, oral or nasal airway placement, bag and mask ventilation, or endotracheal intubation.

A multivariate regression analysis of the measured comorbidity, polysomnography, and oximetry parameters, as well as age, identified three factors that independently linked with a statistically significant increase in the rate of severe PRAE: airway anomaly, underlying cardiac disease, and young age. Patients with an airway anomaly had a 219% increased rate of PRAE, compared with those with no anomaly; patients with underlying cardiac disease had a 109% increased rate, compared with those without cardiac disease; and patients aged younger than 3 years had a 310% higher rate of PRAE, compared with the children aged 6 years or older, while children aged 3-5 years had a 121% higher rate of PRAE, compared with older children.

The study received no commercial funding. Dr. Katz has received honoraria for speaking from Biogen that had no relevance to the study.

mzoler@mdedge.com

SOURCE: Katz SL et al. J Clin Sleep Med. 2020 Jan 15;16(1):41-8.

Underlying cardiac disease, airway anomalies, and younger age each independently boosted the risk of severe perioperative respiratory adverse events (PRAE) in children undergoing adenotonsillectomy to treat obstructive sleep apnea, in a review of 374 patients treated at a single Canadian tertiary-referral center.

In contrast, the analysis failed to show independent, significant effects from any assessed polysomnography or oximetry parameters on the rate of postoperative respiratory complications. The utility of preoperative polysomnography or oximetry for risk stratification is questionable for pediatric patients scheduled to adenotonsillectomy to treat obstructive sleep apnea, wrote Sherri L. Katz, MD, of the University of Ottawa, and associates in a recent report published in the Journal of Clinical Sleep Medicine, although they also added that making these assessments may be “unavoidable” because of their need for diagnosing obstructive sleep apnea and determining the need for surgery.

Despite this caveat, “overall our study results highlight the need to better define the complex interaction between comorbidities, age, nocturnal respiratory events, and gas exchange abnormalities in predicting risk for PRAE” after adenotonsillectomy, the researchers wrote. These findings “are consistent with existing clinical care guidelines,” and “cardiac and craniofacial conditions have been associated with risk of postoperative complications in other studies.”

The analysis used data collected from all children aged 0-18 years who underwent polysomnography assessment followed by adenotonsillectomy at one Canadian tertiary-referral center, Children’s Hospital of Eastern Ontario in Ottawa, during 2010-2016. Their median age was just over 6 years, and 39 patients (10%) were younger than 3 years at the time of their surgery. More than three-quarters of the patients, 286, had at least one identified comorbidity, and nearly half had at least two comorbidities. Polysomnography identified sleep-disordered breathing in 344 of the children (92%), and diagnosed obstructive sleep apnea in 256 (68%), including 148 (43% of the full cohort) with a severe apnea-hypopnea index.

Sixty-six of the children (18%) had at least one severe PRAE that required intervention. Specifically these were either oxygen desaturations requiring intervention or need for airway or ventilatory support with interventions such as jaw thrust, oral or nasal airway placement, bag and mask ventilation, or endotracheal intubation.

A multivariate regression analysis of the measured comorbidity, polysomnography, and oximetry parameters, as well as age, identified three factors that independently linked with a statistically significant increase in the rate of severe PRAE: airway anomaly, underlying cardiac disease, and young age. Patients with an airway anomaly had a 219% increased rate of PRAE, compared with those with no anomaly; patients with underlying cardiac disease had a 109% increased rate, compared with those without cardiac disease; and patients aged younger than 3 years had a 310% higher rate of PRAE, compared with the children aged 6 years or older, while children aged 3-5 years had a 121% higher rate of PRAE, compared with older children.

The study received no commercial funding. Dr. Katz has received honoraria for speaking from Biogen that had no relevance to the study.

mzoler@mdedge.com

SOURCE: Katz SL et al. J Clin Sleep Med. 2020 Jan 15;16(1):41-8.

In this edition of “How I Will Treat My Next Patient,” I review “guidelines for today” and speculate about “guidelines for tomorrow,” highlighting recommendations from the American Society of Clinical Oncology about hereditary cancer testing in epithelial ovarian cancer (OC) and data that support a reexamination of the age at which screening for colorectal cancer (CRC) should begin.

ASCO guidelines on genetic testing in epithelial ovarian cancer

After reviewing 19 studies, including 6 meta-analyses; 11 randomized, controlled trials; and 2 observational studies, an ASCO panel recommended germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes for all women with newly diagnosed epithelial OC, regardless of family history (J Clin Oncol. 2020 Jan 27. doi: 10.1200/JCO.19.02960).

For OC patients with a germline mutation, cascade testing of first- and second-degree relatives was strongly urged. For patients without a germline mutation, the guidelines recommended offering somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants at disease recurrence or after initial therapy and for mismatch repair deficiency (MMRD) in patients with clear cell, endometrioid, or mucinous and potentially other histologic types of OC. The authors cautioned that the discussion of testing results should involve professionals with expertise in the surveillance and management of hereditary cancer syndromes.

The panel said the discovery of germline or somatic pathogenic or likely pathogenic BRCA1/2 variants should lead to considering treatment with Food and Drug Administration–approved poly (ADP-ribose) polymerase inhibitors, including niraparib, olaparib, and rucaparib. Identification of MMRD in a patient with recurrent OC should trigger consideration of treatment with pembrolizumab, consistent with its labeled indications, and surveillance for other malignancies.

The guidelines cautioned that, when patients have variants of uncertain significance on germline testing, “clinical features and family history should inform clinical decision making.” Similarly, the panel made no recommendation regarding testing for or making treatment decisions based on tests for homologous recombination deficiency.
 

How these results influence practice

Every oncologist recognizes that better understanding of cancer biology can guide personalized diagnostic, predictive, prognostic, and therapeutic strategies for patients and their family members.

It is estimated that approximately 25% of all OC is caused by a heritable genetic condition. Germline mutations in BRCA1 and BRCA2 are identified in 13%-15% of patients with OC, and somatic mutations are found in an additional 7%. Perhaps 6% of all ovarian/fallopian tube/peritoneal cancers are caused by mutations in genes other than BRCA1/2. For that reason, germline sequencing should be performed via multigene panels that assess BRCA1/2 and other relevant mutations.

MMDR has been found in 10%-12% of unselected epithelial OC, with increased representation in nonserous histologies. That frequency is high enough to justify testing for it routinely.

Unfortunately, only about 30% of women undergo genetic testing. Given the frequency of molecular abnormalities in OC, this is problematic in every conceivable domain of clinical care for patients and family members. ASCO’s comprehensive, educational guidelines provide a template for shared decision making and utilize resources that are available in almost all clinical settings. For those clinicians who have recommended genetic testing for all epithelial OC patients, these guidelines are practice reaffirming. For the rest of us, they are practice changing.
 

Colorectal cancer cases spike after start of routine screening

Instead of examining CRC incidence by the usual 5- or 10-year age ranges, a group of researchers looked at CRC incidence in 1-year intervals for adults aged 30-60 years in the SEER-18 registry from 2000 to 2015 (JAMA Network Open. 2020 Jan 31. doi: 10.1001/jamanetworkopen.2019.20407). The researchers focused their attention on the transition between age 49 and 50 years, which is when routine screening generally begins and case-finding based on symptoms and signs of CRC alone ideally ends.

The group’s hypothesis was that steep increases in CRC incidence between ages 49 and 50 would be consistent with a high, undetected preclinical case burden in patients aged younger than 50 years and that this “real-world” registry data could help estimate outcomes of screening at younger ages. The researchers found that CRC incidence increased by 46.1% in the transition period from age 49 to 50 years. A majority (93%) of these cases were invasive and, therefore, likely to be clinically relevant. The increase in cancer rates occurred across geographical regions, gender, and race, and likely reflected the impact of screening. The states with the steepest increases in CRC between ages 49 and 50 (Connecticut and Utah) were the states with the first and third highest CRC screening rates for individuals 50 years of age and older.

Stage stratification showed steep increases in incidence in the target age range for localized and regional CRC and for colon and rectal tumors. In the transition between age 49 and 50, the researchers found a significant increase in 5-year relative survival (6.9% absolute increase, 10% relative increase), suggesting that earlier screening had a survival impact, apart from the effects of treatment in cases diagnosed after symptoms occurred.

The authors concluded that their analysis of the transition from age 49 to 50 years provides registry-based data regarding CRC risk among individuals younger than 50, which can add to existing modeling studies to help inform guidelines about the age at which to initiate screening.
 

How these results influence practice

Early-onset CRC (EOCRC) incidence is increasing, with controversy regarding whether average-risk screening should begin before age 50 years. The justification for starting screening at age 50 is that there is a near doubling of incidence from patients aged 45-49 years (34 per 100,000) to those aged 50-54 years (60.2 per 100,000).

However, the increase in CRC incidence beyond age 50 may not be because rates are truly lower among younger individuals but rather because of uneven screening between the two populations. Doubling times for CRCs have been estimated to be perhaps as long as 1,000 days. Because many CRCs are asymptomatic, observed incidence rates of EOCRC in SEER registries do not reflect preclinical CRC case burdens in younger patients.

The current interrogation of SEER-18 data to identify preexisting CRC that was clinically silent in the 1-year interval between age 49 and 50 is highly supportive of a large undiagnosed number of EOCRC cases. In SEER-18, CRC rates increased 46.1% in this 1-year age transition, more than in earlier 1-year age transitions. With almost 93% of cases being invasive, these data suggest a high case burden of preclinical, undetected, clinically relevant EOCRC in younger patients that is not reflected in observed SEER incidence rates examining wider age group intervals.

The dual goals of screening for CRC are to prevent malignant neoplasms by the removal of precancerous polyps and improve cancer-specific survival. The data presented suggest that, by starting average-risk screening at age 50 years, we may be “missing the window.” The 6.9% absolute and 10.1% relative survival increase in the target transition period suggest the authors’ hypothesis is correct.

As in any real-world database survey, the analysis is limited by a lack of specific outcomes data, the inability to determine when the cancers developed, and how long they germinated. Because of those limitations and others, more detailed studies are needed to determine the ideal age at which to begin CRC screening.

Modeling studies incorporating the steep incidence inflection point at 49-50 years can be conducted to estimate the incidence rate increase at, for example, 45 years; the cost-benefit ratio; quality-adjusted life-years gained; and other important endpoints. However, this review of over 170,000 cases of CRC, with a data-completeness rate of over 98%, over the 15-year time frame when CRC screening became common, supports a fresh look at whether it is within our power to improve outcomes for EOCRC patients by using existing technology but applying it earlier.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I review “guidelines for today” and speculate about “guidelines for tomorrow,” highlighting recommendations from the American Society of Clinical Oncology about hereditary cancer testing in epithelial ovarian cancer (OC) and data that support a reexamination of the age at which screening for colorectal cancer (CRC) should begin.

ASCO guidelines on genetic testing in epithelial ovarian cancer

After reviewing 19 studies, including 6 meta-analyses; 11 randomized, controlled trials; and 2 observational studies, an ASCO panel recommended germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes for all women with newly diagnosed epithelial OC, regardless of family history (J Clin Oncol. 2020 Jan 27. doi: 10.1200/JCO.19.02960).

For OC patients with a germline mutation, cascade testing of first- and second-degree relatives was strongly urged. For patients without a germline mutation, the guidelines recommended offering somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants at disease recurrence or after initial therapy and for mismatch repair deficiency (MMRD) in patients with clear cell, endometrioid, or mucinous and potentially other histologic types of OC. The authors cautioned that the discussion of testing results should involve professionals with expertise in the surveillance and management of hereditary cancer syndromes.

The panel said the discovery of germline or somatic pathogenic or likely pathogenic BRCA1/2 variants should lead to considering treatment with Food and Drug Administration–approved poly (ADP-ribose) polymerase inhibitors, including niraparib, olaparib, and rucaparib. Identification of MMRD in a patient with recurrent OC should trigger consideration of treatment with pembrolizumab, consistent with its labeled indications, and surveillance for other malignancies.

The guidelines cautioned that, when patients have variants of uncertain significance on germline testing, “clinical features and family history should inform clinical decision making.” Similarly, the panel made no recommendation regarding testing for or making treatment decisions based on tests for homologous recombination deficiency.
 

How these results influence practice

Every oncologist recognizes that better understanding of cancer biology can guide personalized diagnostic, predictive, prognostic, and therapeutic strategies for patients and their family members.

It is estimated that approximately 25% of all OC is caused by a heritable genetic condition. Germline mutations in BRCA1 and BRCA2 are identified in 13%-15% of patients with OC, and somatic mutations are found in an additional 7%. Perhaps 6% of all ovarian/fallopian tube/peritoneal cancers are caused by mutations in genes other than BRCA1/2. For that reason, germline sequencing should be performed via multigene panels that assess BRCA1/2 and other relevant mutations.

MMDR has been found in 10%-12% of unselected epithelial OC, with increased representation in nonserous histologies. That frequency is high enough to justify testing for it routinely.

Unfortunately, only about 30% of women undergo genetic testing. Given the frequency of molecular abnormalities in OC, this is problematic in every conceivable domain of clinical care for patients and family members. ASCO’s comprehensive, educational guidelines provide a template for shared decision making and utilize resources that are available in almost all clinical settings. For those clinicians who have recommended genetic testing for all epithelial OC patients, these guidelines are practice reaffirming. For the rest of us, they are practice changing.
 

Colorectal cancer cases spike after start of routine screening

Instead of examining CRC incidence by the usual 5- or 10-year age ranges, a group of researchers looked at CRC incidence in 1-year intervals for adults aged 30-60 years in the SEER-18 registry from 2000 to 2015 (JAMA Network Open. 2020 Jan 31. doi: 10.1001/jamanetworkopen.2019.20407). The researchers focused their attention on the transition between age 49 and 50 years, which is when routine screening generally begins and case-finding based on symptoms and signs of CRC alone ideally ends.

The group’s hypothesis was that steep increases in CRC incidence between ages 49 and 50 would be consistent with a high, undetected preclinical case burden in patients aged younger than 50 years and that this “real-world” registry data could help estimate outcomes of screening at younger ages. The researchers found that CRC incidence increased by 46.1% in the transition period from age 49 to 50 years. A majority (93%) of these cases were invasive and, therefore, likely to be clinically relevant. The increase in cancer rates occurred across geographical regions, gender, and race, and likely reflected the impact of screening. The states with the steepest increases in CRC between ages 49 and 50 (Connecticut and Utah) were the states with the first and third highest CRC screening rates for individuals 50 years of age and older.

Stage stratification showed steep increases in incidence in the target age range for localized and regional CRC and for colon and rectal tumors. In the transition between age 49 and 50, the researchers found a significant increase in 5-year relative survival (6.9% absolute increase, 10% relative increase), suggesting that earlier screening had a survival impact, apart from the effects of treatment in cases diagnosed after symptoms occurred.

The authors concluded that their analysis of the transition from age 49 to 50 years provides registry-based data regarding CRC risk among individuals younger than 50, which can add to existing modeling studies to help inform guidelines about the age at which to initiate screening.
 

How these results influence practice

Early-onset CRC (EOCRC) incidence is increasing, with controversy regarding whether average-risk screening should begin before age 50 years. The justification for starting screening at age 50 is that there is a near doubling of incidence from patients aged 45-49 years (34 per 100,000) to those aged 50-54 years (60.2 per 100,000).

However, the increase in CRC incidence beyond age 50 may not be because rates are truly lower among younger individuals but rather because of uneven screening between the two populations. Doubling times for CRCs have been estimated to be perhaps as long as 1,000 days. Because many CRCs are asymptomatic, observed incidence rates of EOCRC in SEER registries do not reflect preclinical CRC case burdens in younger patients.

The current interrogation of SEER-18 data to identify preexisting CRC that was clinically silent in the 1-year interval between age 49 and 50 is highly supportive of a large undiagnosed number of EOCRC cases. In SEER-18, CRC rates increased 46.1% in this 1-year age transition, more than in earlier 1-year age transitions. With almost 93% of cases being invasive, these data suggest a high case burden of preclinical, undetected, clinically relevant EOCRC in younger patients that is not reflected in observed SEER incidence rates examining wider age group intervals.

The dual goals of screening for CRC are to prevent malignant neoplasms by the removal of precancerous polyps and improve cancer-specific survival. The data presented suggest that, by starting average-risk screening at age 50 years, we may be “missing the window.” The 6.9% absolute and 10.1% relative survival increase in the target transition period suggest the authors’ hypothesis is correct.

As in any real-world database survey, the analysis is limited by a lack of specific outcomes data, the inability to determine when the cancers developed, and how long they germinated. Because of those limitations and others, more detailed studies are needed to determine the ideal age at which to begin CRC screening.

Modeling studies incorporating the steep incidence inflection point at 49-50 years can be conducted to estimate the incidence rate increase at, for example, 45 years; the cost-benefit ratio; quality-adjusted life-years gained; and other important endpoints. However, this review of over 170,000 cases of CRC, with a data-completeness rate of over 98%, over the 15-year time frame when CRC screening became common, supports a fresh look at whether it is within our power to improve outcomes for EOCRC patients by using existing technology but applying it earlier.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

In this edition of “How I Will Treat My Next Patient,” I review “guidelines for today” and speculate about “guidelines for tomorrow,” highlighting recommendations from the American Society of Clinical Oncology about hereditary cancer testing in epithelial ovarian cancer (OC) and data that support a reexamination of the age at which screening for colorectal cancer (CRC) should begin.

ASCO guidelines on genetic testing in epithelial ovarian cancer

After reviewing 19 studies, including 6 meta-analyses; 11 randomized, controlled trials; and 2 observational studies, an ASCO panel recommended germline genetic testing for BRCA1, BRCA2, and other ovarian cancer susceptibility genes for all women with newly diagnosed epithelial OC, regardless of family history (J Clin Oncol. 2020 Jan 27. doi: 10.1200/JCO.19.02960).

For OC patients with a germline mutation, cascade testing of first- and second-degree relatives was strongly urged. For patients without a germline mutation, the guidelines recommended offering somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants at disease recurrence or after initial therapy and for mismatch repair deficiency (MMRD) in patients with clear cell, endometrioid, or mucinous and potentially other histologic types of OC. The authors cautioned that the discussion of testing results should involve professionals with expertise in the surveillance and management of hereditary cancer syndromes.

The panel said the discovery of germline or somatic pathogenic or likely pathogenic BRCA1/2 variants should lead to considering treatment with Food and Drug Administration–approved poly (ADP-ribose) polymerase inhibitors, including niraparib, olaparib, and rucaparib. Identification of MMRD in a patient with recurrent OC should trigger consideration of treatment with pembrolizumab, consistent with its labeled indications, and surveillance for other malignancies.

The guidelines cautioned that, when patients have variants of uncertain significance on germline testing, “clinical features and family history should inform clinical decision making.” Similarly, the panel made no recommendation regarding testing for or making treatment decisions based on tests for homologous recombination deficiency.
 

How these results influence practice

Every oncologist recognizes that better understanding of cancer biology can guide personalized diagnostic, predictive, prognostic, and therapeutic strategies for patients and their family members.

It is estimated that approximately 25% of all OC is caused by a heritable genetic condition. Germline mutations in BRCA1 and BRCA2 are identified in 13%-15% of patients with OC, and somatic mutations are found in an additional 7%. Perhaps 6% of all ovarian/fallopian tube/peritoneal cancers are caused by mutations in genes other than BRCA1/2. For that reason, germline sequencing should be performed via multigene panels that assess BRCA1/2 and other relevant mutations.

MMDR has been found in 10%-12% of unselected epithelial OC, with increased representation in nonserous histologies. That frequency is high enough to justify testing for it routinely.

Unfortunately, only about 30% of women undergo genetic testing. Given the frequency of molecular abnormalities in OC, this is problematic in every conceivable domain of clinical care for patients and family members. ASCO’s comprehensive, educational guidelines provide a template for shared decision making and utilize resources that are available in almost all clinical settings. For those clinicians who have recommended genetic testing for all epithelial OC patients, these guidelines are practice reaffirming. For the rest of us, they are practice changing.
 

Colorectal cancer cases spike after start of routine screening

Instead of examining CRC incidence by the usual 5- or 10-year age ranges, a group of researchers looked at CRC incidence in 1-year intervals for adults aged 30-60 years in the SEER-18 registry from 2000 to 2015 (JAMA Network Open. 2020 Jan 31. doi: 10.1001/jamanetworkopen.2019.20407). The researchers focused their attention on the transition between age 49 and 50 years, which is when routine screening generally begins and case-finding based on symptoms and signs of CRC alone ideally ends.

The group’s hypothesis was that steep increases in CRC incidence between ages 49 and 50 would be consistent with a high, undetected preclinical case burden in patients aged younger than 50 years and that this “real-world” registry data could help estimate outcomes of screening at younger ages. The researchers found that CRC incidence increased by 46.1% in the transition period from age 49 to 50 years. A majority (93%) of these cases were invasive and, therefore, likely to be clinically relevant. The increase in cancer rates occurred across geographical regions, gender, and race, and likely reflected the impact of screening. The states with the steepest increases in CRC between ages 49 and 50 (Connecticut and Utah) were the states with the first and third highest CRC screening rates for individuals 50 years of age and older.

Stage stratification showed steep increases in incidence in the target age range for localized and regional CRC and for colon and rectal tumors. In the transition between age 49 and 50, the researchers found a significant increase in 5-year relative survival (6.9% absolute increase, 10% relative increase), suggesting that earlier screening had a survival impact, apart from the effects of treatment in cases diagnosed after symptoms occurred.

The authors concluded that their analysis of the transition from age 49 to 50 years provides registry-based data regarding CRC risk among individuals younger than 50, which can add to existing modeling studies to help inform guidelines about the age at which to initiate screening.
 

How these results influence practice

Early-onset CRC (EOCRC) incidence is increasing, with controversy regarding whether average-risk screening should begin before age 50 years. The justification for starting screening at age 50 is that there is a near doubling of incidence from patients aged 45-49 years (34 per 100,000) to those aged 50-54 years (60.2 per 100,000).

However, the increase in CRC incidence beyond age 50 may not be because rates are truly lower among younger individuals but rather because of uneven screening between the two populations. Doubling times for CRCs have been estimated to be perhaps as long as 1,000 days. Because many CRCs are asymptomatic, observed incidence rates of EOCRC in SEER registries do not reflect preclinical CRC case burdens in younger patients.

The current interrogation of SEER-18 data to identify preexisting CRC that was clinically silent in the 1-year interval between age 49 and 50 is highly supportive of a large undiagnosed number of EOCRC cases. In SEER-18, CRC rates increased 46.1% in this 1-year age transition, more than in earlier 1-year age transitions. With almost 93% of cases being invasive, these data suggest a high case burden of preclinical, undetected, clinically relevant EOCRC in younger patients that is not reflected in observed SEER incidence rates examining wider age group intervals.

The dual goals of screening for CRC are to prevent malignant neoplasms by the removal of precancerous polyps and improve cancer-specific survival. The data presented suggest that, by starting average-risk screening at age 50 years, we may be “missing the window.” The 6.9% absolute and 10.1% relative survival increase in the target transition period suggest the authors’ hypothesis is correct.

As in any real-world database survey, the analysis is limited by a lack of specific outcomes data, the inability to determine when the cancers developed, and how long they germinated. Because of those limitations and others, more detailed studies are needed to determine the ideal age at which to begin CRC screening.

Modeling studies incorporating the steep incidence inflection point at 49-50 years can be conducted to estimate the incidence rate increase at, for example, 45 years; the cost-benefit ratio; quality-adjusted life-years gained; and other important endpoints. However, this review of over 170,000 cases of CRC, with a data-completeness rate of over 98%, over the 15-year time frame when CRC screening became common, supports a fresh look at whether it is within our power to improve outcomes for EOCRC patients by using existing technology but applying it earlier.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

At a follow-up visit, a biopsy of the skin on the fingertips was performed, which showed lichenoid lymphocytic inflammatory infiltrate with associated hyperkeratosis, hypergranulosis, and acanthosis.

No fungal elements were seen. The findings were consistent with lichen planus.

Courtesy Dr. Catalina Matiz

Nail lichen planus (NLP) in children is not a common condition.¹ In a recent series from Chiheb et al., NLP was reported in 90 patients, of which 40% were children; a quarter of the patients reported having extracutaneous involvement as well.² In another childhood LP series,14 % of the children presented with nail disease.³ It can be a severe disease that, if not treated aggressively, may lead to destruction of the nail bed. This condition seems to be more prevalent in boys than girls and more prevalent in African American children.³ Unfortunately, in this patient’s case, the mother was hesitant to use systemic therapy and aggressive treatment was delayed.

Possible but not clear associations with autoimmune conditions such as vitiligo, autoimmune thyroiditis, myasthenia gravis, alopecia areata, thymoma, autoimmune polyendocrinopathy, atopic dermatitis, and lichen nitidus have been described in children with LP.

The clinical characteristics of NLP include nail plate thinning with longitudinal ridging and fissuring, with or without pterygium; trachyonychia; and erythema of the lunula when the nail matrix is involved. When the nail bed is affected, the patient can present with onycholysis with or without subungual hyperkeratosis and violaceous hue of the nail bed.⁴ NLP can have three different clinical presentations described by Tosti et al., which include typical NLP, 20‐nail dystrophy (trachyonychia), and idiopathic nail atrophy. Idiopathic nail atrophy is described solely in children as an acute and rapid progression that leads to destruction of the nail within months, which appears to be the clinical presentation in our patient.

The differential diagnosis of nail dystrophy in children includes infectious processes such as onychomycosis, especially when children present with onycholysis and subungual hyperkeratosis. Because of this, it is recommended to perform a nail culture or submit a sample of nail clippings for microscopic evaluation to confirm the diagnosis of onychomycosis prior to starting systemic therapy in children. Fingernail involvement without toenail involvement is an unusual presentation of onychomycosis.

Twenty-nail dystrophy – also known as trachyonychia – can be caused by several inflammatory skin conditions such as lichen planus, psoriasis, eczema, pemphigus vulgaris, and alopecia areata. Clinically, there is uniformly monomorphic thinning of the nail plate with longitudinal ridging without splitting or pterygium.¹ This is a benign condition and should not cause scarring. About 10% of the cases of 20-nail dystrophy are caused by lichen planus.

Nail psoriasis is characterized by nail pitting, oil spots on the nail plate, leukonychia, subungual hyperkeratosis, and onycholysis, as well as nail crumbling, which were not seen in our patient. Although her initial presentation was of 20-nail dystrophy, which also can be a presentation of nail psoriasis, its rapid evolution with associated nail atrophy and pterygium make it unlikely to be psoriasis in this particular patient.

Patients with pachyonychia congenita – which is a genetic disorder or keratinization caused by mutations on several genes encoding keratin such as K6a, K16, K17, K6b, and possibly K6c – present with nail thickening (pachyonychia) and discoloration of the nails, as well as pincer nails. These patients also present with oral leukokeratosis and focal palmoplantar keratoderma.

The main treatment of lichen planus is potent topical corticosteroids.

For nail disease, topical treatment may not be effective and systemic treatment may be necessary. Systemic corticosteroids have been used in several pediatric series varying from a short course given at a dose of 1- 2 mg/kg per day for 2 weeks to a longer 3-month course followed by tapering.³ There are several protocols of intramuscular triamcinolone at a dose of 0.5 mg/kg in children in once a month injections for about 3 months that have been reported successful with minimal side effects.¹ Other medications reported useful in patients with NLP include dapsone and acitretin. Other treatment options include narrow-band UVB and PUVA.³

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at pdnews@mdedge.com.

References

1. Arch Dermatol. 2001 Aug;137(8):1027-32.

2. Ann Dermatol Venereol. 2015 Jan;142(1):21-5.

3. Pediatr Dermatol. 2014 Jan-Feb;31(1):59-67.

4. Dermatological diseases, in “Nails: Diagnosis, Therapy, and Surgery,” 3rd ed. (Oxford: Elsevier Saunders, 2005, p. 105).

At a follow-up visit, a biopsy of the skin on the fingertips was performed, which showed lichenoid lymphocytic inflammatory infiltrate with associated hyperkeratosis, hypergranulosis, and acanthosis.

No fungal elements were seen. The findings were consistent with lichen planus.

Courtesy Dr. Catalina Matiz

Nail lichen planus (NLP) in children is not a common condition.¹ In a recent series from Chiheb et al., NLP was reported in 90 patients, of which 40% were children; a quarter of the patients reported having extracutaneous involvement as well.² In another childhood LP series,14 % of the children presented with nail disease.³ It can be a severe disease that, if not treated aggressively, may lead to destruction of the nail bed. This condition seems to be more prevalent in boys than girls and more prevalent in African American children.³ Unfortunately, in this patient’s case, the mother was hesitant to use systemic therapy and aggressive treatment was delayed.

Possible but not clear associations with autoimmune conditions such as vitiligo, autoimmune thyroiditis, myasthenia gravis, alopecia areata, thymoma, autoimmune polyendocrinopathy, atopic dermatitis, and lichen nitidus have been described in children with LP.

The clinical characteristics of NLP include nail plate thinning with longitudinal ridging and fissuring, with or without pterygium; trachyonychia; and erythema of the lunula when the nail matrix is involved. When the nail bed is affected, the patient can present with onycholysis with or without subungual hyperkeratosis and violaceous hue of the nail bed.⁴ NLP can have three different clinical presentations described by Tosti et al., which include typical NLP, 20‐nail dystrophy (trachyonychia), and idiopathic nail atrophy. Idiopathic nail atrophy is described solely in children as an acute and rapid progression that leads to destruction of the nail within months, which appears to be the clinical presentation in our patient.

The differential diagnosis of nail dystrophy in children includes infectious processes such as onychomycosis, especially when children present with onycholysis and subungual hyperkeratosis. Because of this, it is recommended to perform a nail culture or submit a sample of nail clippings for microscopic evaluation to confirm the diagnosis of onychomycosis prior to starting systemic therapy in children. Fingernail involvement without toenail involvement is an unusual presentation of onychomycosis.

Twenty-nail dystrophy – also known as trachyonychia – can be caused by several inflammatory skin conditions such as lichen planus, psoriasis, eczema, pemphigus vulgaris, and alopecia areata. Clinically, there is uniformly monomorphic thinning of the nail plate with longitudinal ridging without splitting or pterygium.¹ This is a benign condition and should not cause scarring. About 10% of the cases of 20-nail dystrophy are caused by lichen planus.

Nail psoriasis is characterized by nail pitting, oil spots on the nail plate, leukonychia, subungual hyperkeratosis, and onycholysis, as well as nail crumbling, which were not seen in our patient. Although her initial presentation was of 20-nail dystrophy, which also can be a presentation of nail psoriasis, its rapid evolution with associated nail atrophy and pterygium make it unlikely to be psoriasis in this particular patient.

Patients with pachyonychia congenita – which is a genetic disorder or keratinization caused by mutations on several genes encoding keratin such as K6a, K16, K17, K6b, and possibly K6c – present with nail thickening (pachyonychia) and discoloration of the nails, as well as pincer nails. These patients also present with oral leukokeratosis and focal palmoplantar keratoderma.

The main treatment of lichen planus is potent topical corticosteroids.

For nail disease, topical treatment may not be effective and systemic treatment may be necessary. Systemic corticosteroids have been used in several pediatric series varying from a short course given at a dose of 1- 2 mg/kg per day for 2 weeks to a longer 3-month course followed by tapering.³ There are several protocols of intramuscular triamcinolone at a dose of 0.5 mg/kg in children in once a month injections for about 3 months that have been reported successful with minimal side effects.¹ Other medications reported useful in patients with NLP include dapsone and acitretin. Other treatment options include narrow-band UVB and PUVA.³

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at pdnews@mdedge.com.

References

1. Arch Dermatol. 2001 Aug;137(8):1027-32.

2. Ann Dermatol Venereol. 2015 Jan;142(1):21-5.

3. Pediatr Dermatol. 2014 Jan-Feb;31(1):59-67.

4. Dermatological diseases, in “Nails: Diagnosis, Therapy, and Surgery,” 3rd ed. (Oxford: Elsevier Saunders, 2005, p. 105).

At a follow-up visit, a biopsy of the skin on the fingertips was performed, which showed lichenoid lymphocytic inflammatory infiltrate with associated hyperkeratosis, hypergranulosis, and acanthosis.

No fungal elements were seen. The findings were consistent with lichen planus.

Courtesy Dr. Catalina Matiz

Nail lichen planus (NLP) in children is not a common condition.¹ In a recent series from Chiheb et al., NLP was reported in 90 patients, of which 40% were children; a quarter of the patients reported having extracutaneous involvement as well.² In another childhood LP series,14 % of the children presented with nail disease.³ It can be a severe disease that, if not treated aggressively, may lead to destruction of the nail bed. This condition seems to be more prevalent in boys than girls and more prevalent in African American children.³ Unfortunately, in this patient’s case, the mother was hesitant to use systemic therapy and aggressive treatment was delayed.

Possible but not clear associations with autoimmune conditions such as vitiligo, autoimmune thyroiditis, myasthenia gravis, alopecia areata, thymoma, autoimmune polyendocrinopathy, atopic dermatitis, and lichen nitidus have been described in children with LP.

The clinical characteristics of NLP include nail plate thinning with longitudinal ridging and fissuring, with or without pterygium; trachyonychia; and erythema of the lunula when the nail matrix is involved. When the nail bed is affected, the patient can present with onycholysis with or without subungual hyperkeratosis and violaceous hue of the nail bed.⁴ NLP can have three different clinical presentations described by Tosti et al., which include typical NLP, 20‐nail dystrophy (trachyonychia), and idiopathic nail atrophy. Idiopathic nail atrophy is described solely in children as an acute and rapid progression that leads to destruction of the nail within months, which appears to be the clinical presentation in our patient.

The differential diagnosis of nail dystrophy in children includes infectious processes such as onychomycosis, especially when children present with onycholysis and subungual hyperkeratosis. Because of this, it is recommended to perform a nail culture or submit a sample of nail clippings for microscopic evaluation to confirm the diagnosis of onychomycosis prior to starting systemic therapy in children. Fingernail involvement without toenail involvement is an unusual presentation of onychomycosis.

Twenty-nail dystrophy – also known as trachyonychia – can be caused by several inflammatory skin conditions such as lichen planus, psoriasis, eczema, pemphigus vulgaris, and alopecia areata. Clinically, there is uniformly monomorphic thinning of the nail plate with longitudinal ridging without splitting or pterygium.¹ This is a benign condition and should not cause scarring. About 10% of the cases of 20-nail dystrophy are caused by lichen planus.

Nail psoriasis is characterized by nail pitting, oil spots on the nail plate, leukonychia, subungual hyperkeratosis, and onycholysis, as well as nail crumbling, which were not seen in our patient. Although her initial presentation was of 20-nail dystrophy, which also can be a presentation of nail psoriasis, its rapid evolution with associated nail atrophy and pterygium make it unlikely to be psoriasis in this particular patient.

Patients with pachyonychia congenita – which is a genetic disorder or keratinization caused by mutations on several genes encoding keratin such as K6a, K16, K17, K6b, and possibly K6c – present with nail thickening (pachyonychia) and discoloration of the nails, as well as pincer nails. These patients also present with oral leukokeratosis and focal palmoplantar keratoderma.

The main treatment of lichen planus is potent topical corticosteroids.

For nail disease, topical treatment may not be effective and systemic treatment may be necessary. Systemic corticosteroids have been used in several pediatric series varying from a short course given at a dose of 1- 2 mg/kg per day for 2 weeks to a longer 3-month course followed by tapering.³ There are several protocols of intramuscular triamcinolone at a dose of 0.5 mg/kg in children in once a month injections for about 3 months that have been reported successful with minimal side effects.¹ Other medications reported useful in patients with NLP include dapsone and acitretin. Other treatment options include narrow-band UVB and PUVA.³

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Email her at pdnews@mdedge.com.

References

1. Arch Dermatol. 2001 Aug;137(8):1027-32.

2. Ann Dermatol Venereol. 2015 Jan;142(1):21-5.

3. Pediatr Dermatol. 2014 Jan-Feb;31(1):59-67.

4. Dermatological diseases, in “Nails: Diagnosis, Therapy, and Surgery,” 3rd ed. (Oxford: Elsevier Saunders, 2005, p. 105).

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022

Alcohol use is associated with hepatic steatosis, even after exclusion of heavy drinkers. Binge drinking was associated with a particularly high risk. The results are drawn from a retrospective analysis of the Framingham Heart Study and indicate a possible connection between alcohol use and nonalcoholic fatty liver disease (NAFLD). If confirmed prospectively, the results suggest that alcohol use could be a target for prevention and treatment of presumed NAFLD.

The study was led by Michelle Long, MD, of Boston University, and was published in Clinical Gastroenterology and Hepatology.

Previous studies have produced mixed results with respect to alcohol consumption and NAFLD, with some reporting increased risk with alcohol consumption, and some a beneficial effect of moderate alcohol consumption. Most such studies focused on average daily or weekly alcohol intake, without examining individual differences in alcohol use behavior.

The current work included 2,475 participants from the Offspring and Third Generation Cohorts of the multidetector CT (MDCT) substudy of the Framingham Heart Study. The researchers excluded heavy drinkers, defined as those who had more than 21 drinks (men) or 14 drinks (women) per week.

Of the sample, 17.3% had hepatic steatosis as measured by MDCT. The risk of hepatic steatosis increased from 15.3% to 54.3% along increasing categories of alcohol use.

With each standard deviation increase in the number of alcohol drinks per week, the risk of hepatic steatosis increased by 15% (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29). Of subjects with presumed NAFLD, 25.4% were binge drinkers, defined as four or more drinks per day in women and five or more in men.

A pattern of risky weekly drinking – defined as 8 or more drinks for women or 15 or more for men – was associated with a 45% increase in odds of hepatic steatosis (aOR, 1.45; 95% CI, 1.06-1.98).

An analysis of only current drinkers showed stronger associations between hepatic steatosis and the number of alcoholic drinks per week, risky weekly drinking, and maximum number of drinks in 24 hours.

When the researchers broke down the analysis by beer, wine, or spirit drinkers, they only found a statistically significant association between alcohol consumption and hepatic steatosis in beer drinkers.

The study authors received funding from a range of nonindustry sources. They reported having no relevant financial disclosures.

SOURCE: Long M et al. Clin Gastroenterol Hepatol. 2019 Nov 14. doi: 10.1016/j.cgh.2019.11.022