Conference Coverage

Frequent hypoglycemic episodes were linked to a raised incidence of cardiovascular events in adults with type 2 diabetes in a recent retrospective study, suggesting certain hypoglycemia-associated diabetes drugs should be avoided, an investigator said.

Patients who had more than five hypoglycemic episodes per year had a 61% greater risk of cardiovascular (CV) events, compared with patients with less frequent episodes, according to results of the study.

Although there were fewer strokes among younger patients, the overall increase in cardiovascular event risk held up regardless of age group, according to investigator Aman Rajpal, MD, of Louis Stokes Veterans Affairs Medical Center and Case Western Reserve University, both in Cleveland.

On the basis of these and earlier studies tying hypoglycemia to CV risk, health care providers need to “pay close attention” to low blood sugar and personalize glycemic control targets for each patient based on risk of hypoglycemia, Dr. Rajpal said in a presentation of the study at the virtual annual scientific sessions of the American Diabetes Association.

“Also, this suggests that avoidance of drugs associated with increased risk of hypoglycemia – namely insulin, sulfonylureas, or others – is essential to avoid and minimize the risk of cardiovascular events in this patient population with type 2 diabetes,” said Dr. Rajpal. “Let us remember part of our Hippocratic oath: ‘Above all, do no harm.’ ”
 

Tailoring treatment to mitigate risk

Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, said that results of this study suggest a need to carefully select medical therapy for each individual patient with diabetes in order to mitigate CV risk.

“It’s really about tailoring their drugs to their personal situation,” Dr. Schutta said in an interview.

Although newer diabetes drug classes are associated with low to no risk of hypoglycemia, Dr. Schutta said that there is still a place for drugs such as sulfonylureas in certain situations.

Among sulfonylureas, glyburide comes with a much higher incidence of hypoglycemia, compared with glipizide and glimepiride, according to Dr. Schutta. “I think there’s a role for both drugs, but you have to be very careful, and you have to get the data from your patients.”
 

Hypoglycemia frequency and outcomes

Speculation that hypoglycemia could be linked to adverse CV outcomes was sparked years ago by trials such as ADVANCE. Severe hypoglycemia in that study was associated with a 168% increased risk of death from a CV cause (N Engl J Med. 2010 Oct 7;363:1410-8).

At the time, ADVANCE investigators said they were unable to find evidence that multiple severe hypoglycemia episodes conferred a greater risk of CV events versus a single hypoglycemia episode, though they added that few patients had recurrent events.

“In other words, the association between the number of hypoglycemia events, and adverse CV outcomes is still unclear,” said Dr. Rajpal in his virtual ADA presentation.
 

Potential elevated risks with more than five episodes

To evaluate the association between frequent hypoglycemic episodes (i.e., more than five per year, compared with one to five episodes) and CV events, Dr. Rajpal and colleagues evaluated outcomes data for 4.9 million adults with type 2 diabetes found in a large commercial database including information on patients in 27 U.S. health care networks.

Database records indicated that about 182,000 patients, or nearly 4%, had episodes of hyperglycemia, which Dr. Rajpal said was presumed to mean a plasma glucose level of less than 70 mg/dL.

Characteristics of the patients with more than five hypoglycemic episodes were similar to those with one to five episodes, although they were more likely to be 65 years or older, and were “slightly more likely” to be on insulin, which could possibly precipitate more hypoglycemic episodes in that group, Dr. Rajpal said.
 

Key findings

In the main analysis, Dr. Rajpal said, risk of CV events was significantly increased in those with more than five hypoglycemic episodes, compared with those with one to five episodes, with an odds ratio of 1.61 (95% confidence interval, 1.56-1.66). The incidence of cardiovascular events was 33.1% in those with more than five episodes and 23.5% in those with one to five episodes, according to the data presented.

Risks were also significantly increased specifically for cardiac arrhythmias, cerebrovascular accidents, and MI, Dr. Rajpal said, with ORs of 1.65 (95% CI, 1.9-1.71), 1.38 (95% CI, 1.22-1.56), and 1.43 (95% CI, 1.36-1.50), respectively.

Because individuals in the group with more than five hypoglycemic episodes were more likely to be elderly, Dr. Rajpal said that he and coinvestigators decided to perform an age-specific stratified analysis.

Although cerebral vascular incidence was low in younger patients, risk of CV events overall was nevertheless significantly elevated for those aged 65 years or older, 45-64 years, and 18-44 years, with ORs of 1.69 (95% CI, 1.61-1.7), 1.58 (95% CI, 1.48-1.69), and 1.62 (95% CI, 1.33-1.97).

“The results were still valid in stratified analysis based on different age groups,” Dr. Rajpal said.

Dr. Rajpal and coauthors reported that he had no conflicts of interest related to the research.

SOURCE: Rajpal A et al. ADA 2020, Abstract 161-OR.

Frequent hypoglycemic episodes were linked to a raised incidence of cardiovascular events in adults with type 2 diabetes in a recent retrospective study, suggesting certain hypoglycemia-associated diabetes drugs should be avoided, an investigator said.

Patients who had more than five hypoglycemic episodes per year had a 61% greater risk of cardiovascular (CV) events, compared with patients with less frequent episodes, according to results of the study.

Although there were fewer strokes among younger patients, the overall increase in cardiovascular event risk held up regardless of age group, according to investigator Aman Rajpal, MD, of Louis Stokes Veterans Affairs Medical Center and Case Western Reserve University, both in Cleveland.

On the basis of these and earlier studies tying hypoglycemia to CV risk, health care providers need to “pay close attention” to low blood sugar and personalize glycemic control targets for each patient based on risk of hypoglycemia, Dr. Rajpal said in a presentation of the study at the virtual annual scientific sessions of the American Diabetes Association.

“Also, this suggests that avoidance of drugs associated with increased risk of hypoglycemia – namely insulin, sulfonylureas, or others – is essential to avoid and minimize the risk of cardiovascular events in this patient population with type 2 diabetes,” said Dr. Rajpal. “Let us remember part of our Hippocratic oath: ‘Above all, do no harm.’ ”
 

Tailoring treatment to mitigate risk

Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, said that results of this study suggest a need to carefully select medical therapy for each individual patient with diabetes in order to mitigate CV risk.

“It’s really about tailoring their drugs to their personal situation,” Dr. Schutta said in an interview.

Although newer diabetes drug classes are associated with low to no risk of hypoglycemia, Dr. Schutta said that there is still a place for drugs such as sulfonylureas in certain situations.

Among sulfonylureas, glyburide comes with a much higher incidence of hypoglycemia, compared with glipizide and glimepiride, according to Dr. Schutta. “I think there’s a role for both drugs, but you have to be very careful, and you have to get the data from your patients.”
 

Hypoglycemia frequency and outcomes

Speculation that hypoglycemia could be linked to adverse CV outcomes was sparked years ago by trials such as ADVANCE. Severe hypoglycemia in that study was associated with a 168% increased risk of death from a CV cause (N Engl J Med. 2010 Oct 7;363:1410-8).

At the time, ADVANCE investigators said they were unable to find evidence that multiple severe hypoglycemia episodes conferred a greater risk of CV events versus a single hypoglycemia episode, though they added that few patients had recurrent events.

“In other words, the association between the number of hypoglycemia events, and adverse CV outcomes is still unclear,” said Dr. Rajpal in his virtual ADA presentation.
 

Potential elevated risks with more than five episodes

To evaluate the association between frequent hypoglycemic episodes (i.e., more than five per year, compared with one to five episodes) and CV events, Dr. Rajpal and colleagues evaluated outcomes data for 4.9 million adults with type 2 diabetes found in a large commercial database including information on patients in 27 U.S. health care networks.

Database records indicated that about 182,000 patients, or nearly 4%, had episodes of hyperglycemia, which Dr. Rajpal said was presumed to mean a plasma glucose level of less than 70 mg/dL.

Characteristics of the patients with more than five hypoglycemic episodes were similar to those with one to five episodes, although they were more likely to be 65 years or older, and were “slightly more likely” to be on insulin, which could possibly precipitate more hypoglycemic episodes in that group, Dr. Rajpal said.
 

Key findings

In the main analysis, Dr. Rajpal said, risk of CV events was significantly increased in those with more than five hypoglycemic episodes, compared with those with one to five episodes, with an odds ratio of 1.61 (95% confidence interval, 1.56-1.66). The incidence of cardiovascular events was 33.1% in those with more than five episodes and 23.5% in those with one to five episodes, according to the data presented.

Risks were also significantly increased specifically for cardiac arrhythmias, cerebrovascular accidents, and MI, Dr. Rajpal said, with ORs of 1.65 (95% CI, 1.9-1.71), 1.38 (95% CI, 1.22-1.56), and 1.43 (95% CI, 1.36-1.50), respectively.

Because individuals in the group with more than five hypoglycemic episodes were more likely to be elderly, Dr. Rajpal said that he and coinvestigators decided to perform an age-specific stratified analysis.

Although cerebral vascular incidence was low in younger patients, risk of CV events overall was nevertheless significantly elevated for those aged 65 years or older, 45-64 years, and 18-44 years, with ORs of 1.69 (95% CI, 1.61-1.7), 1.58 (95% CI, 1.48-1.69), and 1.62 (95% CI, 1.33-1.97).

“The results were still valid in stratified analysis based on different age groups,” Dr. Rajpal said.

Dr. Rajpal and coauthors reported that he had no conflicts of interest related to the research.

SOURCE: Rajpal A et al. ADA 2020, Abstract 161-OR.

Frequent hypoglycemic episodes were linked to a raised incidence of cardiovascular events in adults with type 2 diabetes in a recent retrospective study, suggesting certain hypoglycemia-associated diabetes drugs should be avoided, an investigator said.

Patients who had more than five hypoglycemic episodes per year had a 61% greater risk of cardiovascular (CV) events, compared with patients with less frequent episodes, according to results of the study.

Although there were fewer strokes among younger patients, the overall increase in cardiovascular event risk held up regardless of age group, according to investigator Aman Rajpal, MD, of Louis Stokes Veterans Affairs Medical Center and Case Western Reserve University, both in Cleveland.

On the basis of these and earlier studies tying hypoglycemia to CV risk, health care providers need to “pay close attention” to low blood sugar and personalize glycemic control targets for each patient based on risk of hypoglycemia, Dr. Rajpal said in a presentation of the study at the virtual annual scientific sessions of the American Diabetes Association.

“Also, this suggests that avoidance of drugs associated with increased risk of hypoglycemia – namely insulin, sulfonylureas, or others – is essential to avoid and minimize the risk of cardiovascular events in this patient population with type 2 diabetes,” said Dr. Rajpal. “Let us remember part of our Hippocratic oath: ‘Above all, do no harm.’ ”
 

Tailoring treatment to mitigate risk

Mark Schutta, MD, medical director of Penn Rodebaugh Diabetes Center in Philadelphia, said that results of this study suggest a need to carefully select medical therapy for each individual patient with diabetes in order to mitigate CV risk.

“It’s really about tailoring their drugs to their personal situation,” Dr. Schutta said in an interview.

Although newer diabetes drug classes are associated with low to no risk of hypoglycemia, Dr. Schutta said that there is still a place for drugs such as sulfonylureas in certain situations.

Among sulfonylureas, glyburide comes with a much higher incidence of hypoglycemia, compared with glipizide and glimepiride, according to Dr. Schutta. “I think there’s a role for both drugs, but you have to be very careful, and you have to get the data from your patients.”
 

Hypoglycemia frequency and outcomes

Speculation that hypoglycemia could be linked to adverse CV outcomes was sparked years ago by trials such as ADVANCE. Severe hypoglycemia in that study was associated with a 168% increased risk of death from a CV cause (N Engl J Med. 2010 Oct 7;363:1410-8).

At the time, ADVANCE investigators said they were unable to find evidence that multiple severe hypoglycemia episodes conferred a greater risk of CV events versus a single hypoglycemia episode, though they added that few patients had recurrent events.

“In other words, the association between the number of hypoglycemia events, and adverse CV outcomes is still unclear,” said Dr. Rajpal in his virtual ADA presentation.
 

Potential elevated risks with more than five episodes

To evaluate the association between frequent hypoglycemic episodes (i.e., more than five per year, compared with one to five episodes) and CV events, Dr. Rajpal and colleagues evaluated outcomes data for 4.9 million adults with type 2 diabetes found in a large commercial database including information on patients in 27 U.S. health care networks.

Database records indicated that about 182,000 patients, or nearly 4%, had episodes of hyperglycemia, which Dr. Rajpal said was presumed to mean a plasma glucose level of less than 70 mg/dL.

Characteristics of the patients with more than five hypoglycemic episodes were similar to those with one to five episodes, although they were more likely to be 65 years or older, and were “slightly more likely” to be on insulin, which could possibly precipitate more hypoglycemic episodes in that group, Dr. Rajpal said.
 

Key findings

In the main analysis, Dr. Rajpal said, risk of CV events was significantly increased in those with more than five hypoglycemic episodes, compared with those with one to five episodes, with an odds ratio of 1.61 (95% confidence interval, 1.56-1.66). The incidence of cardiovascular events was 33.1% in those with more than five episodes and 23.5% in those with one to five episodes, according to the data presented.

Risks were also significantly increased specifically for cardiac arrhythmias, cerebrovascular accidents, and MI, Dr. Rajpal said, with ORs of 1.65 (95% CI, 1.9-1.71), 1.38 (95% CI, 1.22-1.56), and 1.43 (95% CI, 1.36-1.50), respectively.

Because individuals in the group with more than five hypoglycemic episodes were more likely to be elderly, Dr. Rajpal said that he and coinvestigators decided to perform an age-specific stratified analysis.

Although cerebral vascular incidence was low in younger patients, risk of CV events overall was nevertheless significantly elevated for those aged 65 years or older, 45-64 years, and 18-44 years, with ORs of 1.69 (95% CI, 1.61-1.7), 1.58 (95% CI, 1.48-1.69), and 1.62 (95% CI, 1.33-1.97).

“The results were still valid in stratified analysis based on different age groups,” Dr. Rajpal said.

Dr. Rajpal and coauthors reported that he had no conflicts of interest related to the research.

SOURCE: Rajpal A et al. ADA 2020, Abstract 161-OR.

The national incidence of vulvar melanoma is on the rise in women aged over 60 years, climbing by an average of 2.2% per year during 2000-2016, Maia K. Erickson reported in a poster at the virtual annual meeting of the American Academy of Dermatology.

These are often aggressive malignancies. The 5-year survival following diagnosis of vulvar melanoma in women aged 60 years or older was 39.7%, compared with 61.9% in younger women, according to Ms. Erickson, a visiting research fellow in the department of dermatology at Northwestern University, Chicago.

She presented a population-based study of epidemiologic trends in vulvar melanoma based upon analysis of the National Cancer Institute’s Surveillance, Epidemiology and End Results database. Vulvar melanoma was rare during the study years 2000-2016, with an overall incidence rate of 0.1 cases per 100,000 women. That worked out to 746 analyzable cases. Of note, the incidence rate ratio was 680% higher in older women (age 60 and older).

One reason for the markedly worse 5-year survival in older women was that the predominant histologic subtype of vulvar melanoma in that population was nodular melanoma, accounting for 48% of the cases where a histologic subtype was specified. In contrast, the less-aggressive superficial spreading melanoma subtype prevailed in patients aged under 60 years, accounting for 63% of cases.

About 93% of vulvar melanomas occurred in whites; 63% were local and 8.7% were metastatic.

Ms. Erickson noted that the vulva is the most common site for gynecologic tract melanomas, accounting for 70% of them. And while the female genitalia make up only 1%-2% of body surface area, that’s the anatomic site of up to 7% of all melanomas in women.

She reported having no financial conflicts regarding her study.

bjancin@mdedge.com

The national incidence of vulvar melanoma is on the rise in women aged over 60 years, climbing by an average of 2.2% per year during 2000-2016, Maia K. Erickson reported in a poster at the virtual annual meeting of the American Academy of Dermatology.

These are often aggressive malignancies. The 5-year survival following diagnosis of vulvar melanoma in women aged 60 years or older was 39.7%, compared with 61.9% in younger women, according to Ms. Erickson, a visiting research fellow in the department of dermatology at Northwestern University, Chicago.

She presented a population-based study of epidemiologic trends in vulvar melanoma based upon analysis of the National Cancer Institute’s Surveillance, Epidemiology and End Results database. Vulvar melanoma was rare during the study years 2000-2016, with an overall incidence rate of 0.1 cases per 100,000 women. That worked out to 746 analyzable cases. Of note, the incidence rate ratio was 680% higher in older women (age 60 and older).

One reason for the markedly worse 5-year survival in older women was that the predominant histologic subtype of vulvar melanoma in that population was nodular melanoma, accounting for 48% of the cases where a histologic subtype was specified. In contrast, the less-aggressive superficial spreading melanoma subtype prevailed in patients aged under 60 years, accounting for 63% of cases.

About 93% of vulvar melanomas occurred in whites; 63% were local and 8.7% were metastatic.

Ms. Erickson noted that the vulva is the most common site for gynecologic tract melanomas, accounting for 70% of them. And while the female genitalia make up only 1%-2% of body surface area, that’s the anatomic site of up to 7% of all melanomas in women.

She reported having no financial conflicts regarding her study.

bjancin@mdedge.com

The national incidence of vulvar melanoma is on the rise in women aged over 60 years, climbing by an average of 2.2% per year during 2000-2016, Maia K. Erickson reported in a poster at the virtual annual meeting of the American Academy of Dermatology.

These are often aggressive malignancies. The 5-year survival following diagnosis of vulvar melanoma in women aged 60 years or older was 39.7%, compared with 61.9% in younger women, according to Ms. Erickson, a visiting research fellow in the department of dermatology at Northwestern University, Chicago.

She presented a population-based study of epidemiologic trends in vulvar melanoma based upon analysis of the National Cancer Institute’s Surveillance, Epidemiology and End Results database. Vulvar melanoma was rare during the study years 2000-2016, with an overall incidence rate of 0.1 cases per 100,000 women. That worked out to 746 analyzable cases. Of note, the incidence rate ratio was 680% higher in older women (age 60 and older).

One reason for the markedly worse 5-year survival in older women was that the predominant histologic subtype of vulvar melanoma in that population was nodular melanoma, accounting for 48% of the cases where a histologic subtype was specified. In contrast, the less-aggressive superficial spreading melanoma subtype prevailed in patients aged under 60 years, accounting for 63% of cases.

About 93% of vulvar melanomas occurred in whites; 63% were local and 8.7% were metastatic.

Ms. Erickson noted that the vulva is the most common site for gynecologic tract melanomas, accounting for 70% of them. And while the female genitalia make up only 1%-2% of body surface area, that’s the anatomic site of up to 7% of all melanomas in women.

She reported having no financial conflicts regarding her study.

bjancin@mdedge.com

There appear to be no differences in efficacy or safety between pulse and continuous regimens of terbinafine and no differences between pulse and continuous regimens of itraconazole for dermatophyte toenail onychomycosis, results from a systematic review and network meta-analysis showed.

“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”

In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.

For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.

“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”

They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”

The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.

dbrunk@mdedge.com

SOURCE: Gupta A et al. AAD 20, Abstract 16014.

There appear to be no differences in efficacy or safety between pulse and continuous regimens of terbinafine and no differences between pulse and continuous regimens of itraconazole for dermatophyte toenail onychomycosis, results from a systematic review and network meta-analysis showed.

“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”

In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.

For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.

“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”

They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”

The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.

dbrunk@mdedge.com

SOURCE: Gupta A et al. AAD 20, Abstract 16014.

There appear to be no differences in efficacy or safety between pulse and continuous regimens of terbinafine and no differences between pulse and continuous regimens of itraconazole for dermatophyte toenail onychomycosis, results from a systematic review and network meta-analysis showed.

“Previous meta-analyses of pulse and continuous therapies have generated ambiguous results,” study authors led by Aditya K. Gupta, MD, PhD, wrote in a poster abstract presented at the virtual annual meeting of the American Academy of Dermatology. “There are few head-to-head clinical studies and no meta-analyses comparing regimens of terbinafine to regimens of itraconazole.”

In what is believed to be the first study of its kind, Dr. Gupta, professor of dermatology at the University of Toronto, and colleagues used network meta-analysis to compare pulse and continuous systemic therapies for toenail onychomycosis. They used PubMed to search for randomized, controlled trials of oral antifungal treatments for the condition in patients aged 18 years and older that included data on mycologic cure, complete cure, adverse events, and dropout rates. Treatment effects were based on intention-to-treat cure rates, and the researchers excluded studies of ketoconazole and griseofulvin since they are no longer indicated for the condition.

For their network meta-analysis, Dr. Gupta and colleagues evaluated 22 studies from 20 publications that included 4,205 randomized patients. Data on complete cure were excluded because of a lack of studies. When the researchers compared all treatments to placebo, the likelihood of mycologic cure did not differ significantly between continuous and pulse regimens for terbinafine and itraconazole. Compared with placebo, the most successful treatments were continuous terbinafine 250 mg daily for 24 weeks (risk ratio of achieving mycologic cure, 11.0) and continuous terbinafine 250 mg daily for 16 weeks (RR, 8.90). The researchers also observed no significant differences in the likelihood of adverse events between any continuous and pulse regimens of terbinafine, itraconazole, and fluconazole.

“Although continuous terbinafine 250 mg for 24 weeks was significantly more likely to produce mycologic cure than continuous itraconazole 200 mg for 12 weeks and weekly fluconazole (150-450 mg), it is not significantly different from the other included treatments,” Dr. Gupta and colleagues wrote in the abstract. “Considering the fungal life cycle, pulse therapy should theoretically be as effective as, or more effective than, continuous therapies: the sudden high concentration of an antifungal drug eliminates hyphae, sparing already-present spores. During the ‘off’ portion, these spores may germinate and be eliminated during the next pulse. Continuous therapy spares the spores, allowing them to germinate once treatment ends.”

They went on to note that, in clinical practice, “neither continuous nor pulse therapy is necessarily better. It is possible that the drug concentration in the nail is maintained during the ‘off’ period of pulse therapy. In both therapies, it may be that residual spores that have not been eliminated by the end of therapy are left to germinate, possibly contributing to the recalcitrant nature of onychomycosis.”

The study was awarded fourth place in the AAD’s 2020 poster awards. Dr. Gupta disclosed that he is a clinical trials investigator for Moberg Pharma and Bausch Health Canada and a speaker for Bausch Health Canada.

dbrunk@mdedge.com

SOURCE: Gupta A et al. AAD 20, Abstract 16014.

A new analysis of 300 patients with posttraumatic headache confirmed some long-suspected risk factors for persistent headache, including history of medication overuse or psychological symptoms, new parathyroid hormone–associated comorbidities, and history of migraine. It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.

“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.

He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.

Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.

“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
 

Defining risk factors

The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.

A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
 

Identifying patient subgroups

The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”

Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.

The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.

A new analysis of 300 patients with posttraumatic headache confirmed some long-suspected risk factors for persistent headache, including history of medication overuse or psychological symptoms, new parathyroid hormone–associated comorbidities, and history of migraine. It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.

“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.

He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.

Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.

“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
 

Defining risk factors

The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.

A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
 

Identifying patient subgroups

The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”

Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.

The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.

A new analysis of 300 patients with posttraumatic headache confirmed some long-suspected risk factors for persistent headache, including history of medication overuse or psychological symptoms, new parathyroid hormone–associated comorbidities, and history of migraine. It also revealed a surprisingly high frequency of misdiagnosis. The original sample included 500 patients drawn from the Stanford Research Repository Cohort Discovery Tool, but a review found 200 records that were misdiagnosed and had to be excluded.

“It’s very easy to label someone who suffered a head injury and say this is the reason why they have this (headache),” said lead author Tommy Chan, MBBS, a headache fellow in the department of neurology at Stanford (Calif.) University, in an interview. Such patients are often seen by ED or primary care physicians who do not have a lot of experience with posttraumatic headache, and that can lead to negative consequences if a low-pressure headache is mistaken as stemming from a skull fracture. “It’s a very different treatment plan for one versus the other,” said Dr. Chan in an interview.

He noted that it can help to take a patient history that includes the preaccident headache frequency and determine if there was a change in frequency post injury.

Dr. Chan presented the results at the virtual annual meeting of the American Headache Society.

“The results are what one might expect, although we haven’t studied it enough to really know. We haven’t systematically characterized these risk factors for chronic posttraumatic headache very well, [so] it’s useful to have this information,” said Andrew Charles, MD, professor neurology at the University of California, Los Angeles, and director of the UCLA Goldberg Migraine Program, who was not involved in the study. However, Dr. Charles emphasized the need to confirm the results prospectively.
 

Defining risk factors

The analysis found that a history of migraines, medication overuse, psychological disorders, and new posttraumatic headache–associated comorbidities were all associated with a greater risk for persistent posttraumatic headache. None of those came as a surprise, “but we live in a world where medicine is practiced based on evidence, and providers want to see data to support that. I think that this will help with resource allocation. It’s important to address [a patient’s] overuse of medications, or if they’re having psychological symptoms,” said Dr. Chan.

A total of 150 patients in the analysis had acute posttraumatic headache (mean duration, 0.7 months) while 150 had persistent posttraumatic headache (mean duration, 24 months; P < .00001). Clinical factors associated with risk of persistent headache included a history migraine (relative risk, 2.4; P < .0001), a previous head injury (odds ratio, 5.8; P < .0001), medication overuse (RR, 2.6; P < .0001), preexisting psychological history (OR, 5; P < .0001), and new posttraumatic headache–associated comorbidities, such as vertigo or posttraumatic stress disorder (RR, 9.8; P < .0001).
 

Identifying patient subgroups

The researchers also identified four subcategories of patients with persistent posttraumatic headache, each with differing risk factors and clinical characteristics. It’s too soon to use these identifiers to make clinical recommendations, but Dr. Chan hopes that further study of these groups will be informative. “It might point us toward (the idea) that each patient population is actually different, even within the chronic persistent posttraumatic headache population, we can’t group them all under the same umbrella term. If we can tease out that a patient has truly had a head injury, but no history of migraine, no overuse of medication, no psychological history, and no other associated symptoms, this would be a very interesting population to study because they would help us understand the pathophysiology [of persistent posttraumatic headache].”

Although the study was conducted by defining persistent posttraumatic headache as lasting at least 3 months, Dr. Chan took issue with that commonly held definition. That choice is arbitrary, with no pathophysiological basis or data to support it, and is based more on clinical trials testing preventative treatments. But when it is used in clinical practice, it can muddy communication with patients. “When this timeline is told to a patient, and when it’s not achieved, they might become disappointed. We should not put too much emphasis on time. Everybody is different,” he said.

The study did not receive any funding. Dr. Chan had no relevant financial disclosures. Dr. Charles consults for consults for Amgen, BioHaven, Eli Lilly, Novartis, and Lundbeck.

The majority of patients with early-stage unfavorable Hodgkin lymphoma respond well enough to a current standard regimen of four cycles of chemotherapy and can skip the additional radiotherapy that is normally included in the combined modality treatment, say experts reporting the final results from an international phase 3 randomized trial dubbed HD17.

“Most patients with this disease will not need radiotherapy any longer,” concluded first author Peter Borchmann, MD, assistant medical director in the department of hematology/oncology at the University Hospital Cologne (Germany).

Dr. Borchmann was speaking online as part of the virtual edition of the European Hematology Association 25th Annual Congress 2020.

“Importantly, the mortality of patients with early-stage unfavorable Hodgkin lymphoma in the HD17 study did not differ from the normal healthy German population, and this is the first time we have had this finding in one of our studies,” he emphasized.

Dr. Borchmann added that positron emission tomography imaging is key in deciding which patients can skip radiation.

“We conclude from the HD17 trial that the combined modality concept can and should be replaced by a PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma,” he said.

“The vast majority of early-stage unfavorable Hodgkin lymphoma patients can be treated with the brief and highly effective 2+2 chemotherapy alone,” he added.

Therefore, he continued, “PET-guided 2+2 chemotherapy is the new standard of care for the German Hodgkin study group,” which conducted the trial.

The use of both chemotherapy and radiation has long been a standard approach to treatment, and this combined modality treatment is highly effective, Dr. Borchmann explained. But it can cause long-term damage, and the known longer-term negative effects of radiotherapy, such as cardiovascular disease and second malignancies, are a particular concern because patients with early-stage Hodgkin lymphoma are relatively young, with a median age of around 30 years at disease onset.

An expert approached for comment said that the momentum to skip radiotherapy when possible is an ongoing issue, and importantly, this study adds to those efforts.

“The treatment of Hodgkin lymphoma has moved for many years now to less radiation therapy, and this trend will continue with the results of this study,” commented John G. Gribben, MD, director of the Stem Cell Transplantation Program and medical director of the North East London Cancer Research Network Centre at Barts Cancer Center of Excellence and the London School of Medicine.

“We have moved to lower doses and involved fields with the intent of decreasing toxicity, and particularly long-term toxicity from radiotherapy,” he said in an interview. 

HD17 study details  

For the multicenter, phase 3 HD17 trial, Dr. Borchmann and colleagues turned to PET to identify patients who had and had not responded well to chemotherapy (PET negative and PET positive) and to determine if those who had responded well could safely avoid radiotherapy without compromising efficacy.

“We wanted to determine if we could reduce the treatment intensity by omission of radiotherapy in patients who respond very well to the systemic treatment, so who have a complete metabolic remission after the chemotherapy,” Dr. Borchmann said.

The 2+2 treatment approach includes two cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and two subsequent cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

The trial enrolled 1,100 patients with newly diagnosed Hodgkin lymphoma between January 2012 and March 2017. Of these, 979 patients had confirmed PET results, with 651 (66.5%) found to be PET negative, defined as having a Deauville score (DS) of less than 3 (DS3); 238 (24.3%) were DS3, and 90 (9.2%) were DS4.

The study met its primary endpoint of noninferiority in progression-free survival (PFS) at 5 years, with a PFS of 95.1% in the PET-guided group (n = 447), compared with 97.3% in the standard combined-modality treatment group (n = 428), over a median observation time of 45 months, for a difference of 2.2% (P = .12).

“We found that the survival levels were very high, and we can safely conclude the noninferiority of the PET-guided approach in PET-negative patients,” Dr. Borchmann said.

A further analysis showed that the 597 PET-negative patients who did not receive radiotherapy because of their PET status had 5-year PFS that was noninferior to the combined modality group (95.9% vs. 97.7%, respectively; P = .20).

And among 646 patients who received the 2+2 regimen plus radiotherapy, of those confirmed as PET positive (n = 328), the estimated 5-year PFS was significantly lower (94.2%), compared with those determined to be PET negative (n = 318; 97.6%; hazard ratio, 3.03).

A cut-off of DS4 for positivity was associated with a stronger effect, with a lower estimated 5-year PFS of 81.6% vs. 98.8% for DS3 patients and 97.6% for DS less than 3 (P < .0001).

“Only DS4 has a prognostic impact, but not DS3,” Dr. Borchmann said. “DS4 positivity indicates a relevant risk for treatment failure, however, there are few patients in this risk group (9.2% in this trial).”

The 5-year overall survival rates in an intent-to-treat analysis were 98.8% in the standard combined modality group and 98.4% in the PET-guided group.

With a median observation time of 47 months, there have been 10 fatal events in the trial out of 1,100 patients, including two Hodgkin lymphoma-related events and one treatment-related death.

“Overall, Hodgkin lymphoma or treatment-related mortality rates were extremely low,” Dr. Borchmann said.

The study was funded by Deutsche Krebshilfe. Dr. Borchmann and Dr. Gribben have reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

The majority of patients with early-stage unfavorable Hodgkin lymphoma respond well enough to a current standard regimen of four cycles of chemotherapy and can skip the additional radiotherapy that is normally included in the combined modality treatment, say experts reporting the final results from an international phase 3 randomized trial dubbed HD17.

“Most patients with this disease will not need radiotherapy any longer,” concluded first author Peter Borchmann, MD, assistant medical director in the department of hematology/oncology at the University Hospital Cologne (Germany).

Dr. Borchmann was speaking online as part of the virtual edition of the European Hematology Association 25th Annual Congress 2020.

“Importantly, the mortality of patients with early-stage unfavorable Hodgkin lymphoma in the HD17 study did not differ from the normal healthy German population, and this is the first time we have had this finding in one of our studies,” he emphasized.

Dr. Borchmann added that positron emission tomography imaging is key in deciding which patients can skip radiation.

“We conclude from the HD17 trial that the combined modality concept can and should be replaced by a PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma,” he said.

“The vast majority of early-stage unfavorable Hodgkin lymphoma patients can be treated with the brief and highly effective 2+2 chemotherapy alone,” he added.

Therefore, he continued, “PET-guided 2+2 chemotherapy is the new standard of care for the German Hodgkin study group,” which conducted the trial.

The use of both chemotherapy and radiation has long been a standard approach to treatment, and this combined modality treatment is highly effective, Dr. Borchmann explained. But it can cause long-term damage, and the known longer-term negative effects of radiotherapy, such as cardiovascular disease and second malignancies, are a particular concern because patients with early-stage Hodgkin lymphoma are relatively young, with a median age of around 30 years at disease onset.

An expert approached for comment said that the momentum to skip radiotherapy when possible is an ongoing issue, and importantly, this study adds to those efforts.

“The treatment of Hodgkin lymphoma has moved for many years now to less radiation therapy, and this trend will continue with the results of this study,” commented John G. Gribben, MD, director of the Stem Cell Transplantation Program and medical director of the North East London Cancer Research Network Centre at Barts Cancer Center of Excellence and the London School of Medicine.

“We have moved to lower doses and involved fields with the intent of decreasing toxicity, and particularly long-term toxicity from radiotherapy,” he said in an interview. 

HD17 study details  

For the multicenter, phase 3 HD17 trial, Dr. Borchmann and colleagues turned to PET to identify patients who had and had not responded well to chemotherapy (PET negative and PET positive) and to determine if those who had responded well could safely avoid radiotherapy without compromising efficacy.

“We wanted to determine if we could reduce the treatment intensity by omission of radiotherapy in patients who respond very well to the systemic treatment, so who have a complete metabolic remission after the chemotherapy,” Dr. Borchmann said.

The 2+2 treatment approach includes two cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and two subsequent cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

The trial enrolled 1,100 patients with newly diagnosed Hodgkin lymphoma between January 2012 and March 2017. Of these, 979 patients had confirmed PET results, with 651 (66.5%) found to be PET negative, defined as having a Deauville score (DS) of less than 3 (DS3); 238 (24.3%) were DS3, and 90 (9.2%) were DS4.

The study met its primary endpoint of noninferiority in progression-free survival (PFS) at 5 years, with a PFS of 95.1% in the PET-guided group (n = 447), compared with 97.3% in the standard combined-modality treatment group (n = 428), over a median observation time of 45 months, for a difference of 2.2% (P = .12).

“We found that the survival levels were very high, and we can safely conclude the noninferiority of the PET-guided approach in PET-negative patients,” Dr. Borchmann said.

A further analysis showed that the 597 PET-negative patients who did not receive radiotherapy because of their PET status had 5-year PFS that was noninferior to the combined modality group (95.9% vs. 97.7%, respectively; P = .20).

And among 646 patients who received the 2+2 regimen plus radiotherapy, of those confirmed as PET positive (n = 328), the estimated 5-year PFS was significantly lower (94.2%), compared with those determined to be PET negative (n = 318; 97.6%; hazard ratio, 3.03).

A cut-off of DS4 for positivity was associated with a stronger effect, with a lower estimated 5-year PFS of 81.6% vs. 98.8% for DS3 patients and 97.6% for DS less than 3 (P < .0001).

“Only DS4 has a prognostic impact, but not DS3,” Dr. Borchmann said. “DS4 positivity indicates a relevant risk for treatment failure, however, there are few patients in this risk group (9.2% in this trial).”

The 5-year overall survival rates in an intent-to-treat analysis were 98.8% in the standard combined modality group and 98.4% in the PET-guided group.

With a median observation time of 47 months, there have been 10 fatal events in the trial out of 1,100 patients, including two Hodgkin lymphoma-related events and one treatment-related death.

“Overall, Hodgkin lymphoma or treatment-related mortality rates were extremely low,” Dr. Borchmann said.

The study was funded by Deutsche Krebshilfe. Dr. Borchmann and Dr. Gribben have reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

The majority of patients with early-stage unfavorable Hodgkin lymphoma respond well enough to a current standard regimen of four cycles of chemotherapy and can skip the additional radiotherapy that is normally included in the combined modality treatment, say experts reporting the final results from an international phase 3 randomized trial dubbed HD17.

“Most patients with this disease will not need radiotherapy any longer,” concluded first author Peter Borchmann, MD, assistant medical director in the department of hematology/oncology at the University Hospital Cologne (Germany).

Dr. Borchmann was speaking online as part of the virtual edition of the European Hematology Association 25th Annual Congress 2020.

“Importantly, the mortality of patients with early-stage unfavorable Hodgkin lymphoma in the HD17 study did not differ from the normal healthy German population, and this is the first time we have had this finding in one of our studies,” he emphasized.

Dr. Borchmann added that positron emission tomography imaging is key in deciding which patients can skip radiation.

“We conclude from the HD17 trial that the combined modality concept can and should be replaced by a PET-guided omission of radiotherapy for patients with newly diagnosed early-stage unfavorable Hodgkin lymphoma,” he said.

“The vast majority of early-stage unfavorable Hodgkin lymphoma patients can be treated with the brief and highly effective 2+2 chemotherapy alone,” he added.

Therefore, he continued, “PET-guided 2+2 chemotherapy is the new standard of care for the German Hodgkin study group,” which conducted the trial.

The use of both chemotherapy and radiation has long been a standard approach to treatment, and this combined modality treatment is highly effective, Dr. Borchmann explained. But it can cause long-term damage, and the known longer-term negative effects of radiotherapy, such as cardiovascular disease and second malignancies, are a particular concern because patients with early-stage Hodgkin lymphoma are relatively young, with a median age of around 30 years at disease onset.

An expert approached for comment said that the momentum to skip radiotherapy when possible is an ongoing issue, and importantly, this study adds to those efforts.

“The treatment of Hodgkin lymphoma has moved for many years now to less radiation therapy, and this trend will continue with the results of this study,” commented John G. Gribben, MD, director of the Stem Cell Transplantation Program and medical director of the North East London Cancer Research Network Centre at Barts Cancer Center of Excellence and the London School of Medicine.

“We have moved to lower doses and involved fields with the intent of decreasing toxicity, and particularly long-term toxicity from radiotherapy,” he said in an interview. 

HD17 study details  

For the multicenter, phase 3 HD17 trial, Dr. Borchmann and colleagues turned to PET to identify patients who had and had not responded well to chemotherapy (PET negative and PET positive) and to determine if those who had responded well could safely avoid radiotherapy without compromising efficacy.

“We wanted to determine if we could reduce the treatment intensity by omission of radiotherapy in patients who respond very well to the systemic treatment, so who have a complete metabolic remission after the chemotherapy,” Dr. Borchmann said.

The 2+2 treatment approach includes two cycles of eBEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and two subsequent cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine).

The trial enrolled 1,100 patients with newly diagnosed Hodgkin lymphoma between January 2012 and March 2017. Of these, 979 patients had confirmed PET results, with 651 (66.5%) found to be PET negative, defined as having a Deauville score (DS) of less than 3 (DS3); 238 (24.3%) were DS3, and 90 (9.2%) were DS4.

The study met its primary endpoint of noninferiority in progression-free survival (PFS) at 5 years, with a PFS of 95.1% in the PET-guided group (n = 447), compared with 97.3% in the standard combined-modality treatment group (n = 428), over a median observation time of 45 months, for a difference of 2.2% (P = .12).

“We found that the survival levels were very high, and we can safely conclude the noninferiority of the PET-guided approach in PET-negative patients,” Dr. Borchmann said.

A further analysis showed that the 597 PET-negative patients who did not receive radiotherapy because of their PET status had 5-year PFS that was noninferior to the combined modality group (95.9% vs. 97.7%, respectively; P = .20).

And among 646 patients who received the 2+2 regimen plus radiotherapy, of those confirmed as PET positive (n = 328), the estimated 5-year PFS was significantly lower (94.2%), compared with those determined to be PET negative (n = 318; 97.6%; hazard ratio, 3.03).

A cut-off of DS4 for positivity was associated with a stronger effect, with a lower estimated 5-year PFS of 81.6% vs. 98.8% for DS3 patients and 97.6% for DS less than 3 (P < .0001).

“Only DS4 has a prognostic impact, but not DS3,” Dr. Borchmann said. “DS4 positivity indicates a relevant risk for treatment failure, however, there are few patients in this risk group (9.2% in this trial).”

The 5-year overall survival rates in an intent-to-treat analysis were 98.8% in the standard combined modality group and 98.4% in the PET-guided group.

With a median observation time of 47 months, there have been 10 fatal events in the trial out of 1,100 patients, including two Hodgkin lymphoma-related events and one treatment-related death.

“Overall, Hodgkin lymphoma or treatment-related mortality rates were extremely low,” Dr. Borchmann said.

The study was funded by Deutsche Krebshilfe. Dr. Borchmann and Dr. Gribben have reported no relevant financial relationships.
 

A version of this article originally appeared on Medscape.com.

Few patients with episodic migraine, and even fewer with chronic migraine, receive optimal treatment, new research shows.

Results from a survey study showed less than 8% of patients with episodic migraine and less than 2% of patients with chronic migraine were able to overcome four key treatment barriers associated with optimal migraine management. These included current medical consultation, appropriate diagnosis, minimally adequate acute and preventive pharmacologic treatment (if indicated), and absence of acute medication overdose.

The researchers also evaluated any potential impact of race, ethnicity, and sociodemographic factors on these barriers.

“While chronic migraine was associated with higher rates of consulting, only 1.8% of respondents with chronic migraine traversed all four barriers compared with 8.5% of those with episodic migraine,” the investigators, led by Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine of Yeshiva University in New York City, noted.

The study was presented at the virtual annual meeting of the American Headache Society.

Ongoing challenges

Migraineurs’ challenges include receiving an appropriate diagnosis and finding effective acute and preventive treatments, the researchers noted. Many patients do not receive optimal care. Previous research by Dr. Buse and colleagues showed that general clinicians were less likely to provide an appropriate diagnosis of migraine compared with headache specialists.

Among patients with chronic migraine who consulted headache specialists, most did not receive an accurate diagnosis of chronic migraine. Data also indicate that a minority, approximately 34%, of patients with chronic migraine used preventive pharmacologic treatments.

The investigators analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to determine the proportion of patients who overcame four prespecified barriers to good outcomes.

Eligible participants met modified International Classification of Headache Disorders (3rd edition) criteria for migraine, had Migraine Disability Assessment Scores (MIDAS) of grade II or higher, and provided data on health insurance status. In addition, all eligible participants had to be receiving appropriate treatment for either episodic or chronic migraine.

In all, 16,789 participants met criteria for migraine. Of this group, 9,184 patients had a MIDAS score of grade II or higher and reported health insurance status. In this subgroup, 7,930 (86.3%) patients had episodic migraine and 1,254 (13.7%) had chronic migraine.

A total of 2,187 (27.6%) patients with episodic migraine and 512 (40.8%) patients with chronic migraine were under the care of a healthcare professional. Of this group, 1,655 patients with episodic migraine (75.7%) and 168 with chronic migraine (32.8%) reported receiving an appropriate diagnosis.

Of participants who successfully overcame the first two optimal management barriers—a consultation with a healthcare professional and an appropriate diagnosis—1,133 (68.5%) episodic migraineurs and 113 (67.3%) chronic migraineurs reported receiving minimally adequate acute treatment.

Furthermore, 1,430 (86.4%) episodic migraineurs and 127 (75.6%) chronic migraineurs reported receiving minimally adequate preventive medication treatment. In addition, 982 (59.3%) episodic migraineurs and 88 (52.4%) chronic migraineurs received minimally adequate acute and preventive treatment.

Acute medication overuse was relatively common, the investigators reported. A total of 310 (31.6%) patients with episodic migraine and 66 (75%) patients with chronic migraine met criteria for acute medication overuse.

“Overuse of acute medication for migraine in people with chronic migraine is a serious concern and is associated with increased risks of migraine progression, headache-related disability, and anxiety and depression. Active patient management and education is important to reduce the likelihood of medication overuse,” said Dr. Buse.

Among all eligible respondents, only 672 (8.5%) patients with episodic migraine and 22 (1.8%) with chronic migraine overcame all four barriers to optimal care.

The researchers found no significant effect of ethnicity or race on the likelihood of overcoming any barrier, but they acknowledged that participation bias might have contributed to this lack of difference. Higher annual household income was significantly associated with high likelihood of surmounting all four barriers.

“The analysis of sociodemographics revealed that female sex and higher annual household income showed a strong relationship with likelihood of obtaining an accurate episodic migraine or chronic migraine diagnosis,” said Dr. Buse.

“Although the reasons for this are not clear, it may be that women are more likely to convey the full scope of their symptoms during consultation. Additionally, the known prevalence of migraine in women may influence healthcare providers by reducing suspicion of chronic migraine in men,” she added.

The CaMEO Study was funded by Allergan (now AbbVie). Dr. Buse reports receiving grant support and honoraria from Allergan, Amgen, Biohaven, Eli Lilly and Co, and Promius. She also receives compensation for work on the editorial board of Current Pain and Headache Reports.

This article first appeared on Medscape.com.

Few patients with episodic migraine, and even fewer with chronic migraine, receive optimal treatment, new research shows.

Results from a survey study showed less than 8% of patients with episodic migraine and less than 2% of patients with chronic migraine were able to overcome four key treatment barriers associated with optimal migraine management. These included current medical consultation, appropriate diagnosis, minimally adequate acute and preventive pharmacologic treatment (if indicated), and absence of acute medication overdose.

The researchers also evaluated any potential impact of race, ethnicity, and sociodemographic factors on these barriers.

“While chronic migraine was associated with higher rates of consulting, only 1.8% of respondents with chronic migraine traversed all four barriers compared with 8.5% of those with episodic migraine,” the investigators, led by Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine of Yeshiva University in New York City, noted.

The study was presented at the virtual annual meeting of the American Headache Society.

Ongoing challenges

Migraineurs’ challenges include receiving an appropriate diagnosis and finding effective acute and preventive treatments, the researchers noted. Many patients do not receive optimal care. Previous research by Dr. Buse and colleagues showed that general clinicians were less likely to provide an appropriate diagnosis of migraine compared with headache specialists.

Among patients with chronic migraine who consulted headache specialists, most did not receive an accurate diagnosis of chronic migraine. Data also indicate that a minority, approximately 34%, of patients with chronic migraine used preventive pharmacologic treatments.

The investigators analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to determine the proportion of patients who overcame four prespecified barriers to good outcomes.

Eligible participants met modified International Classification of Headache Disorders (3rd edition) criteria for migraine, had Migraine Disability Assessment Scores (MIDAS) of grade II or higher, and provided data on health insurance status. In addition, all eligible participants had to be receiving appropriate treatment for either episodic or chronic migraine.

In all, 16,789 participants met criteria for migraine. Of this group, 9,184 patients had a MIDAS score of grade II or higher and reported health insurance status. In this subgroup, 7,930 (86.3%) patients had episodic migraine and 1,254 (13.7%) had chronic migraine.

A total of 2,187 (27.6%) patients with episodic migraine and 512 (40.8%) patients with chronic migraine were under the care of a healthcare professional. Of this group, 1,655 patients with episodic migraine (75.7%) and 168 with chronic migraine (32.8%) reported receiving an appropriate diagnosis.

Of participants who successfully overcame the first two optimal management barriers—a consultation with a healthcare professional and an appropriate diagnosis—1,133 (68.5%) episodic migraineurs and 113 (67.3%) chronic migraineurs reported receiving minimally adequate acute treatment.

Furthermore, 1,430 (86.4%) episodic migraineurs and 127 (75.6%) chronic migraineurs reported receiving minimally adequate preventive medication treatment. In addition, 982 (59.3%) episodic migraineurs and 88 (52.4%) chronic migraineurs received minimally adequate acute and preventive treatment.

Acute medication overuse was relatively common, the investigators reported. A total of 310 (31.6%) patients with episodic migraine and 66 (75%) patients with chronic migraine met criteria for acute medication overuse.

“Overuse of acute medication for migraine in people with chronic migraine is a serious concern and is associated with increased risks of migraine progression, headache-related disability, and anxiety and depression. Active patient management and education is important to reduce the likelihood of medication overuse,” said Dr. Buse.

Among all eligible respondents, only 672 (8.5%) patients with episodic migraine and 22 (1.8%) with chronic migraine overcame all four barriers to optimal care.

The researchers found no significant effect of ethnicity or race on the likelihood of overcoming any barrier, but they acknowledged that participation bias might have contributed to this lack of difference. Higher annual household income was significantly associated with high likelihood of surmounting all four barriers.

“The analysis of sociodemographics revealed that female sex and higher annual household income showed a strong relationship with likelihood of obtaining an accurate episodic migraine or chronic migraine diagnosis,” said Dr. Buse.

“Although the reasons for this are not clear, it may be that women are more likely to convey the full scope of their symptoms during consultation. Additionally, the known prevalence of migraine in women may influence healthcare providers by reducing suspicion of chronic migraine in men,” she added.

The CaMEO Study was funded by Allergan (now AbbVie). Dr. Buse reports receiving grant support and honoraria from Allergan, Amgen, Biohaven, Eli Lilly and Co, and Promius. She also receives compensation for work on the editorial board of Current Pain and Headache Reports.

This article first appeared on Medscape.com.

Few patients with episodic migraine, and even fewer with chronic migraine, receive optimal treatment, new research shows.

Results from a survey study showed less than 8% of patients with episodic migraine and less than 2% of patients with chronic migraine were able to overcome four key treatment barriers associated with optimal migraine management. These included current medical consultation, appropriate diagnosis, minimally adequate acute and preventive pharmacologic treatment (if indicated), and absence of acute medication overdose.

The researchers also evaluated any potential impact of race, ethnicity, and sociodemographic factors on these barriers.

“While chronic migraine was associated with higher rates of consulting, only 1.8% of respondents with chronic migraine traversed all four barriers compared with 8.5% of those with episodic migraine,” the investigators, led by Dawn C. Buse, PhD, clinical professor of neurology at Albert Einstein College of Medicine of Yeshiva University in New York City, noted.

The study was presented at the virtual annual meeting of the American Headache Society.

Ongoing challenges

Migraineurs’ challenges include receiving an appropriate diagnosis and finding effective acute and preventive treatments, the researchers noted. Many patients do not receive optimal care. Previous research by Dr. Buse and colleagues showed that general clinicians were less likely to provide an appropriate diagnosis of migraine compared with headache specialists.

Among patients with chronic migraine who consulted headache specialists, most did not receive an accurate diagnosis of chronic migraine. Data also indicate that a minority, approximately 34%, of patients with chronic migraine used preventive pharmacologic treatments.

The investigators analyzed data from the Chronic Migraine Epidemiology and Outcomes (CaMEO) study to determine the proportion of patients who overcame four prespecified barriers to good outcomes.

Eligible participants met modified International Classification of Headache Disorders (3rd edition) criteria for migraine, had Migraine Disability Assessment Scores (MIDAS) of grade II or higher, and provided data on health insurance status. In addition, all eligible participants had to be receiving appropriate treatment for either episodic or chronic migraine.

In all, 16,789 participants met criteria for migraine. Of this group, 9,184 patients had a MIDAS score of grade II or higher and reported health insurance status. In this subgroup, 7,930 (86.3%) patients had episodic migraine and 1,254 (13.7%) had chronic migraine.

A total of 2,187 (27.6%) patients with episodic migraine and 512 (40.8%) patients with chronic migraine were under the care of a healthcare professional. Of this group, 1,655 patients with episodic migraine (75.7%) and 168 with chronic migraine (32.8%) reported receiving an appropriate diagnosis.

Of participants who successfully overcame the first two optimal management barriers—a consultation with a healthcare professional and an appropriate diagnosis—1,133 (68.5%) episodic migraineurs and 113 (67.3%) chronic migraineurs reported receiving minimally adequate acute treatment.

Furthermore, 1,430 (86.4%) episodic migraineurs and 127 (75.6%) chronic migraineurs reported receiving minimally adequate preventive medication treatment. In addition, 982 (59.3%) episodic migraineurs and 88 (52.4%) chronic migraineurs received minimally adequate acute and preventive treatment.

Acute medication overuse was relatively common, the investigators reported. A total of 310 (31.6%) patients with episodic migraine and 66 (75%) patients with chronic migraine met criteria for acute medication overuse.

“Overuse of acute medication for migraine in people with chronic migraine is a serious concern and is associated with increased risks of migraine progression, headache-related disability, and anxiety and depression. Active patient management and education is important to reduce the likelihood of medication overuse,” said Dr. Buse.

Among all eligible respondents, only 672 (8.5%) patients with episodic migraine and 22 (1.8%) with chronic migraine overcame all four barriers to optimal care.

The researchers found no significant effect of ethnicity or race on the likelihood of overcoming any barrier, but they acknowledged that participation bias might have contributed to this lack of difference. Higher annual household income was significantly associated with high likelihood of surmounting all four barriers.

“The analysis of sociodemographics revealed that female sex and higher annual household income showed a strong relationship with likelihood of obtaining an accurate episodic migraine or chronic migraine diagnosis,” said Dr. Buse.

“Although the reasons for this are not clear, it may be that women are more likely to convey the full scope of their symptoms during consultation. Additionally, the known prevalence of migraine in women may influence healthcare providers by reducing suspicion of chronic migraine in men,” she added.

The CaMEO Study was funded by Allergan (now AbbVie). Dr. Buse reports receiving grant support and honoraria from Allergan, Amgen, Biohaven, Eli Lilly and Co, and Promius. She also receives compensation for work on the editorial board of Current Pain and Headache Reports.

This article first appeared on Medscape.com.

Use of a robotics platform provides a surgeon with more information so they can make better decisions, especially in challenging situations of primary and revisional bariatric surgery, according to Cheguevara Afaneh, MD, of New York–Presbyterian Hospital and Weill Cornell Medical Center, New York.

“The value of modern technology is to be able to do the most difficult cases in a much simpler format,” he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.

Dr. Afaneh shared examples of how robotic assistance can help surgeons address challenges in bariatric surgery clinical practice, including managing super- and super-super-obese patients, dealing with gastroesophageal reflux disease (GERD), and negating the impact of surgical assistant experience.

“Super-obese patients pose more of a challenge interoperatively for both the surgeon and the assistant,” Dr. Afaneh noted. He and colleagues conducted a study of perioperative outcomes and found no significant differences between morbidly obese and super-obese patients in perioperative morbidity or operating time when a robotic platform was used.

The benefits to the surgeon when using robotic assistance in super-obese patients include effortless navigation of the abdominal wall, the ability to execute complex maneuvers in a challenging environment, and the security of a stable platform with no assistant fatigue, Dr. Afaneh emphasized. “When you are using the robotic platform, you are negating a lot of the patient factors” and fatigue factors that make bariatric surgery in super-obese and super-super-obese patients especially difficult, he said.

For example, in a patient who weighed nearly 500 pounds, pulling up on the stomach to get behind the actual stomach is easier because assistant fatigue is not a factor, so the surgeon can take more time and prevent a more difficult dissection, he said. In addition, Dr. Afaneh’s research showed no difference in operative time, and that the robot assistance outcomes were reproducible across a range of body mass index categories.

Robotic assistance also allows for comparable outcomes in surgeons with less experience, notably in revisional surgery, said Dr. Afaneh. He reviewed data from his first year of experience in revisional procedures using robotic assistance to his partners’ more than 20 years of laparoscopic experience. He found no significant differences in operative time, complications, or conversions to open procedures.

However, the more important message from the study was that less experienced surgeons were able to safely perform some of the most difficult revisional procedures without increasing morbidity, compared with more experienced surgeons. The data suggest that, with robotic assistance, surgeons early in their career can take on some of the bigger cases and expect outcomes similar to those of more experienced surgeons, Dr. Afaneh said.

Robotics has demonstrated improved outcomes in managing patients with GERD, which has become a common problem after bariatric surgery, noted Dr. Afaneh. When he and his colleagues reviewed data from their center on robotic-assisted approaches to GERD after bariatric surgery, they found that, even in primary magnetic sphincter operations, “robotics maintains comparable outcomes in revisional sleeve gastrectomy fields,” he said.

Another notable benefit of robotics in bariatric surgery is the negation of the “assistant effect,” said Dr. Afaneh. Often, less experienced surgeons are matched with less experienced assistants. “We took a look at the use of the robotic in cases of complex GI surgeries,” he said. They compared laparoscopic and robotic cases and stratified them by third-year assistant or fellow. “If you had a fellow, the operative time dropped by half an hour for laparoscopic cases, but the time was no different in robotics cases,” regardless of the use of fellow or third-year assistant, he said.

“The robotic platform allows you to assist yourself,” and allows for full surgeon autonomy, Dr. Afaneh emphasized. “You are the best person at predicting your next step.” The robotics platform also serves as a teaching tool. “For those who teach, there is no added morbidity based on the assistance of the trainee,” he said. In addition, the improved visualization of robotics “allows for better appreciation of scarred tissue planes and more precise suturing,” he noted.

Overall, “one of the values of the robotic platform is shortening the learning curve,” Dr. Afaneh said. He reviewed data from his fellows and himself, and found no difference in operative times. “My mentee was able to achieve operative times as good as my third year in practice. The robotic platform shaved off several years of learning experience,” he said. Dr. Afaneh’s operative times also decreased with robotics, which shows how experienced surgeons learn from this technology, he said.

Dr. Afaneh disclosed serving as a consultant for Intuitive Surgical.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Use of a robotics platform provides a surgeon with more information so they can make better decisions, especially in challenging situations of primary and revisional bariatric surgery, according to Cheguevara Afaneh, MD, of New York–Presbyterian Hospital and Weill Cornell Medical Center, New York.

“The value of modern technology is to be able to do the most difficult cases in a much simpler format,” he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.

Dr. Afaneh shared examples of how robotic assistance can help surgeons address challenges in bariatric surgery clinical practice, including managing super- and super-super-obese patients, dealing with gastroesophageal reflux disease (GERD), and negating the impact of surgical assistant experience.

“Super-obese patients pose more of a challenge interoperatively for both the surgeon and the assistant,” Dr. Afaneh noted. He and colleagues conducted a study of perioperative outcomes and found no significant differences between morbidly obese and super-obese patients in perioperative morbidity or operating time when a robotic platform was used.

The benefits to the surgeon when using robotic assistance in super-obese patients include effortless navigation of the abdominal wall, the ability to execute complex maneuvers in a challenging environment, and the security of a stable platform with no assistant fatigue, Dr. Afaneh emphasized. “When you are using the robotic platform, you are negating a lot of the patient factors” and fatigue factors that make bariatric surgery in super-obese and super-super-obese patients especially difficult, he said.

For example, in a patient who weighed nearly 500 pounds, pulling up on the stomach to get behind the actual stomach is easier because assistant fatigue is not a factor, so the surgeon can take more time and prevent a more difficult dissection, he said. In addition, Dr. Afaneh’s research showed no difference in operative time, and that the robot assistance outcomes were reproducible across a range of body mass index categories.

Robotic assistance also allows for comparable outcomes in surgeons with less experience, notably in revisional surgery, said Dr. Afaneh. He reviewed data from his first year of experience in revisional procedures using robotic assistance to his partners’ more than 20 years of laparoscopic experience. He found no significant differences in operative time, complications, or conversions to open procedures.

However, the more important message from the study was that less experienced surgeons were able to safely perform some of the most difficult revisional procedures without increasing morbidity, compared with more experienced surgeons. The data suggest that, with robotic assistance, surgeons early in their career can take on some of the bigger cases and expect outcomes similar to those of more experienced surgeons, Dr. Afaneh said.

Robotics has demonstrated improved outcomes in managing patients with GERD, which has become a common problem after bariatric surgery, noted Dr. Afaneh. When he and his colleagues reviewed data from their center on robotic-assisted approaches to GERD after bariatric surgery, they found that, even in primary magnetic sphincter operations, “robotics maintains comparable outcomes in revisional sleeve gastrectomy fields,” he said.

Another notable benefit of robotics in bariatric surgery is the negation of the “assistant effect,” said Dr. Afaneh. Often, less experienced surgeons are matched with less experienced assistants. “We took a look at the use of the robotic in cases of complex GI surgeries,” he said. They compared laparoscopic and robotic cases and stratified them by third-year assistant or fellow. “If you had a fellow, the operative time dropped by half an hour for laparoscopic cases, but the time was no different in robotics cases,” regardless of the use of fellow or third-year assistant, he said.

“The robotic platform allows you to assist yourself,” and allows for full surgeon autonomy, Dr. Afaneh emphasized. “You are the best person at predicting your next step.” The robotics platform also serves as a teaching tool. “For those who teach, there is no added morbidity based on the assistance of the trainee,” he said. In addition, the improved visualization of robotics “allows for better appreciation of scarred tissue planes and more precise suturing,” he noted.

Overall, “one of the values of the robotic platform is shortening the learning curve,” Dr. Afaneh said. He reviewed data from his fellows and himself, and found no difference in operative times. “My mentee was able to achieve operative times as good as my third year in practice. The robotic platform shaved off several years of learning experience,” he said. Dr. Afaneh’s operative times also decreased with robotics, which shows how experienced surgeons learn from this technology, he said.

Dr. Afaneh disclosed serving as a consultant for Intuitive Surgical.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Use of a robotics platform provides a surgeon with more information so they can make better decisions, especially in challenging situations of primary and revisional bariatric surgery, according to Cheguevara Afaneh, MD, of New York–Presbyterian Hospital and Weill Cornell Medical Center, New York.

“The value of modern technology is to be able to do the most difficult cases in a much simpler format,” he said in a presentation at the virtual Annual Minimally Invasive Surgery Symposium by Global Academy for Medical Education.

Dr. Afaneh shared examples of how robotic assistance can help surgeons address challenges in bariatric surgery clinical practice, including managing super- and super-super-obese patients, dealing with gastroesophageal reflux disease (GERD), and negating the impact of surgical assistant experience.

“Super-obese patients pose more of a challenge interoperatively for both the surgeon and the assistant,” Dr. Afaneh noted. He and colleagues conducted a study of perioperative outcomes and found no significant differences between morbidly obese and super-obese patients in perioperative morbidity or operating time when a robotic platform was used.

The benefits to the surgeon when using robotic assistance in super-obese patients include effortless navigation of the abdominal wall, the ability to execute complex maneuvers in a challenging environment, and the security of a stable platform with no assistant fatigue, Dr. Afaneh emphasized. “When you are using the robotic platform, you are negating a lot of the patient factors” and fatigue factors that make bariatric surgery in super-obese and super-super-obese patients especially difficult, he said.

For example, in a patient who weighed nearly 500 pounds, pulling up on the stomach to get behind the actual stomach is easier because assistant fatigue is not a factor, so the surgeon can take more time and prevent a more difficult dissection, he said. In addition, Dr. Afaneh’s research showed no difference in operative time, and that the robot assistance outcomes were reproducible across a range of body mass index categories.

Robotic assistance also allows for comparable outcomes in surgeons with less experience, notably in revisional surgery, said Dr. Afaneh. He reviewed data from his first year of experience in revisional procedures using robotic assistance to his partners’ more than 20 years of laparoscopic experience. He found no significant differences in operative time, complications, or conversions to open procedures.

However, the more important message from the study was that less experienced surgeons were able to safely perform some of the most difficult revisional procedures without increasing morbidity, compared with more experienced surgeons. The data suggest that, with robotic assistance, surgeons early in their career can take on some of the bigger cases and expect outcomes similar to those of more experienced surgeons, Dr. Afaneh said.

Robotics has demonstrated improved outcomes in managing patients with GERD, which has become a common problem after bariatric surgery, noted Dr. Afaneh. When he and his colleagues reviewed data from their center on robotic-assisted approaches to GERD after bariatric surgery, they found that, even in primary magnetic sphincter operations, “robotics maintains comparable outcomes in revisional sleeve gastrectomy fields,” he said.

Another notable benefit of robotics in bariatric surgery is the negation of the “assistant effect,” said Dr. Afaneh. Often, less experienced surgeons are matched with less experienced assistants. “We took a look at the use of the robotic in cases of complex GI surgeries,” he said. They compared laparoscopic and robotic cases and stratified them by third-year assistant or fellow. “If you had a fellow, the operative time dropped by half an hour for laparoscopic cases, but the time was no different in robotics cases,” regardless of the use of fellow or third-year assistant, he said.

“The robotic platform allows you to assist yourself,” and allows for full surgeon autonomy, Dr. Afaneh emphasized. “You are the best person at predicting your next step.” The robotics platform also serves as a teaching tool. “For those who teach, there is no added morbidity based on the assistance of the trainee,” he said. In addition, the improved visualization of robotics “allows for better appreciation of scarred tissue planes and more precise suturing,” he noted.

Overall, “one of the values of the robotic platform is shortening the learning curve,” Dr. Afaneh said. He reviewed data from his fellows and himself, and found no difference in operative times. “My mentee was able to achieve operative times as good as my third year in practice. The robotic platform shaved off several years of learning experience,” he said. Dr. Afaneh’s operative times also decreased with robotics, which shows how experienced surgeons learn from this technology, he said.

Dr. Afaneh disclosed serving as a consultant for Intuitive Surgical.

Global Academy for Medical Education and this news organization are owned by the same parent company.

Patients who underwent conversion to a laparoscopic sleeve gastrectomy after a previous laparoscopic adjustable gastric banding procedure experienced similar weight loss with either a one- or two-step procedure, a study of 78 patients showed.

“Laparoscopic adjustable gastric banding (LAGB) has largely fallen out of favor, likely related to variable efficacy in weight reduction coupled with poor effectiveness in reducing obesity related comorbidities like type 2 diabetes and hypercholesterolemia,” Vasu Chirumamilla, MD, of Westchester Medical Center, Valhalla, N.Y., and colleagues wrote in a poster presented at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

LAGB also can cause complications including, slippage, erosion, and gastric pouch dilation; subsequently many patients undergo conversion to laparoscopic sleeve gastrectomy (LSG). However, the impact of a one-step vs. two-step conversion procedure on patient weight loss remains unclear, the researchers said.

To compare weight loss after the two types of procedures, the researchers reviewed data from 78 patients (71 women) aged 15-74 years treated between 2013 and 2018 at a multi-surgeon, private practice bariatric surgery center. All patients had a history of LAGB; 31 underwent conversion to LSG in one stage, and 47 underwent conversion in two stages. Weight loss, defined as the percentage excess weight loss, was the primary endpoint.

The average excess weight loss was 44% for patients in both the one-stage and two-stage groups, and body mass index decreased by 8.9 points and 8.8 points, respectively, in the two groups, the researchers wrote.

Patients in the two-stage group experienced a significant increase in body mass index (P = .008) during the time between band removal to sleeve gastrectomy, which was an average of 207 days, they said.

The findings were limited in part by the small sample size and retrospective design, and more data are needed to compare complication rates in one-stage and two-stage procedures, the researchers noted. However, the results showed “no difference in excess weight loss in patients converted from laparoscopic adjustable gastric band to sleeve gastrectomy in one-stage versus a two-stage procedure,” they concluded.

“LAGB used to be a very popular weight loss procedure – bands were placed in a great deal of patients,” Dr. Chirumamilla said in an interview. “Now those patients are presenting with increasing frequency to bariatric surgeons with band complications or weight regain. The volume for LSG is increasing and results in percentage excess weight loss of approximately 65% versus approximately 42% for LAGB,” he said. A goal of the study was to provide patients and the surgeons with a more informed approach to performing and consenting to the particular operation, he added.

“The results have not surprised us, because as long as done by experienced surgeons on compliant patients the weight loss outcomes from the day of surgery onward should be equivalent,” Dr. Chirumamilla explained. “We were also not surprised to find that patients undergoing a two-stage conversion gained weight before their second-stage sleeve gastrectomy.”

The bottom line for clinicians is that “patients getting a conversion from band to sleeve in one-stage versus two-stages experience the same percentage excess body weight loss from time of surgery,” although two-stage patients do gain weight while awaiting their second-stage sleeve gastrectomy, Dr. Chirumamilla said.

“More research is needed to compare short- and long-term complications rates between one-stage and two-stage conversions. The ideal research situation would be a randomized, multicenter, large volume study to reduce bias,” he noted.

Dr. Chirumamilla’s collaborators included Akia Caine MD, Zachary Ballinger, Rebecca Castro, Thomas Cerabona MD, and Ashutosh Kaul MD, of the surgical group Advanced Surgeons at nygetfit.com.

Global Academy for Medical Education and this news organization are owned by the same parent company. The study received no outside funding. The researchers had no financial conflicts to disclose.
 

SOURCE: Chirumamilla V et al. MISS 2020. Poster PA-14.

Patients who underwent conversion to a laparoscopic sleeve gastrectomy after a previous laparoscopic adjustable gastric banding procedure experienced similar weight loss with either a one- or two-step procedure, a study of 78 patients showed.

“Laparoscopic adjustable gastric banding (LAGB) has largely fallen out of favor, likely related to variable efficacy in weight reduction coupled with poor effectiveness in reducing obesity related comorbidities like type 2 diabetes and hypercholesterolemia,” Vasu Chirumamilla, MD, of Westchester Medical Center, Valhalla, N.Y., and colleagues wrote in a poster presented at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

LAGB also can cause complications including, slippage, erosion, and gastric pouch dilation; subsequently many patients undergo conversion to laparoscopic sleeve gastrectomy (LSG). However, the impact of a one-step vs. two-step conversion procedure on patient weight loss remains unclear, the researchers said.

To compare weight loss after the two types of procedures, the researchers reviewed data from 78 patients (71 women) aged 15-74 years treated between 2013 and 2018 at a multi-surgeon, private practice bariatric surgery center. All patients had a history of LAGB; 31 underwent conversion to LSG in one stage, and 47 underwent conversion in two stages. Weight loss, defined as the percentage excess weight loss, was the primary endpoint.

The average excess weight loss was 44% for patients in both the one-stage and two-stage groups, and body mass index decreased by 8.9 points and 8.8 points, respectively, in the two groups, the researchers wrote.

Patients in the two-stage group experienced a significant increase in body mass index (P = .008) during the time between band removal to sleeve gastrectomy, which was an average of 207 days, they said.

The findings were limited in part by the small sample size and retrospective design, and more data are needed to compare complication rates in one-stage and two-stage procedures, the researchers noted. However, the results showed “no difference in excess weight loss in patients converted from laparoscopic adjustable gastric band to sleeve gastrectomy in one-stage versus a two-stage procedure,” they concluded.

“LAGB used to be a very popular weight loss procedure – bands were placed in a great deal of patients,” Dr. Chirumamilla said in an interview. “Now those patients are presenting with increasing frequency to bariatric surgeons with band complications or weight regain. The volume for LSG is increasing and results in percentage excess weight loss of approximately 65% versus approximately 42% for LAGB,” he said. A goal of the study was to provide patients and the surgeons with a more informed approach to performing and consenting to the particular operation, he added.

“The results have not surprised us, because as long as done by experienced surgeons on compliant patients the weight loss outcomes from the day of surgery onward should be equivalent,” Dr. Chirumamilla explained. “We were also not surprised to find that patients undergoing a two-stage conversion gained weight before their second-stage sleeve gastrectomy.”

The bottom line for clinicians is that “patients getting a conversion from band to sleeve in one-stage versus two-stages experience the same percentage excess body weight loss from time of surgery,” although two-stage patients do gain weight while awaiting their second-stage sleeve gastrectomy, Dr. Chirumamilla said.

“More research is needed to compare short- and long-term complications rates between one-stage and two-stage conversions. The ideal research situation would be a randomized, multicenter, large volume study to reduce bias,” he noted.

Dr. Chirumamilla’s collaborators included Akia Caine MD, Zachary Ballinger, Rebecca Castro, Thomas Cerabona MD, and Ashutosh Kaul MD, of the surgical group Advanced Surgeons at nygetfit.com.

Global Academy for Medical Education and this news organization are owned by the same parent company. The study received no outside funding. The researchers had no financial conflicts to disclose.
 

SOURCE: Chirumamilla V et al. MISS 2020. Poster PA-14.

Patients who underwent conversion to a laparoscopic sleeve gastrectomy after a previous laparoscopic adjustable gastric banding procedure experienced similar weight loss with either a one- or two-step procedure, a study of 78 patients showed.

“Laparoscopic adjustable gastric banding (LAGB) has largely fallen out of favor, likely related to variable efficacy in weight reduction coupled with poor effectiveness in reducing obesity related comorbidities like type 2 diabetes and hypercholesterolemia,” Vasu Chirumamilla, MD, of Westchester Medical Center, Valhalla, N.Y., and colleagues wrote in a poster presented at the virtual Annual Minimally Invasive Surgery Symposium sponsored by Global Academy for Medical Education.

LAGB also can cause complications including, slippage, erosion, and gastric pouch dilation; subsequently many patients undergo conversion to laparoscopic sleeve gastrectomy (LSG). However, the impact of a one-step vs. two-step conversion procedure on patient weight loss remains unclear, the researchers said.

To compare weight loss after the two types of procedures, the researchers reviewed data from 78 patients (71 women) aged 15-74 years treated between 2013 and 2018 at a multi-surgeon, private practice bariatric surgery center. All patients had a history of LAGB; 31 underwent conversion to LSG in one stage, and 47 underwent conversion in two stages. Weight loss, defined as the percentage excess weight loss, was the primary endpoint.

The average excess weight loss was 44% for patients in both the one-stage and two-stage groups, and body mass index decreased by 8.9 points and 8.8 points, respectively, in the two groups, the researchers wrote.

Patients in the two-stage group experienced a significant increase in body mass index (P = .008) during the time between band removal to sleeve gastrectomy, which was an average of 207 days, they said.

The findings were limited in part by the small sample size and retrospective design, and more data are needed to compare complication rates in one-stage and two-stage procedures, the researchers noted. However, the results showed “no difference in excess weight loss in patients converted from laparoscopic adjustable gastric band to sleeve gastrectomy in one-stage versus a two-stage procedure,” they concluded.

“LAGB used to be a very popular weight loss procedure – bands were placed in a great deal of patients,” Dr. Chirumamilla said in an interview. “Now those patients are presenting with increasing frequency to bariatric surgeons with band complications or weight regain. The volume for LSG is increasing and results in percentage excess weight loss of approximately 65% versus approximately 42% for LAGB,” he said. A goal of the study was to provide patients and the surgeons with a more informed approach to performing and consenting to the particular operation, he added.

“The results have not surprised us, because as long as done by experienced surgeons on compliant patients the weight loss outcomes from the day of surgery onward should be equivalent,” Dr. Chirumamilla explained. “We were also not surprised to find that patients undergoing a two-stage conversion gained weight before their second-stage sleeve gastrectomy.”

The bottom line for clinicians is that “patients getting a conversion from band to sleeve in one-stage versus two-stages experience the same percentage excess body weight loss from time of surgery,” although two-stage patients do gain weight while awaiting their second-stage sleeve gastrectomy, Dr. Chirumamilla said.

“More research is needed to compare short- and long-term complications rates between one-stage and two-stage conversions. The ideal research situation would be a randomized, multicenter, large volume study to reduce bias,” he noted.

Dr. Chirumamilla’s collaborators included Akia Caine MD, Zachary Ballinger, Rebecca Castro, Thomas Cerabona MD, and Ashutosh Kaul MD, of the surgical group Advanced Surgeons at nygetfit.com.

Global Academy for Medical Education and this news organization are owned by the same parent company. The study received no outside funding. The researchers had no financial conflicts to disclose.
 

SOURCE: Chirumamilla V et al. MISS 2020. Poster PA-14.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

“The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura,” said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. “This study highlights the importance of monitoring severe migraine to potentially prevent dementia.”
 

A national register-based study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

“To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura,” Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. “There was a 50% higher dementia rate in individuals who had any migraine diagnosis,” Dr. Islamoska said.

“We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura,” she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. “The dementia rate was higher if individuals had more frequent hospital contacts with migraine.”

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

“The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines,” Dr. Islamoska said. “Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals.”

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, “thus our results only apply to migraine that is severe enough to require a hospital contact,” Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. “We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient’s burden and course of disease,” Dr. Islamoska said.

“Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia,” Dr. Islamoska said. “In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results.”
 

‘Surprising’ findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. “Vanishingly small amounts of attention have been paid to migraine as a potential risk factor,” he said. However, he called the results “surprising” based on his own clinical experience. “I actually had a sense that migraine was somehow protective against Alzheimer’s or other kinds of dementias.”

He questioned if the migraine-dementia link could be a “reporting artifact” of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are “intriguing” and raise important questions about migraine therapy and dementia risk.

“If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms,” Dr. Charles said. “It’s something we should be thinking about in terms of preventing longer-term consequences of this disorder.”

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.

The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.

“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.

The findings in favor of total body irradiation were pronounced enough that the study was halted early by a safety committee, she added.

Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.

Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”

Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.

“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.

“I think it is very important to better identify those who really need total body irradiation in the future,” she added.

In an interview, Dr. Izraeli agreed.

“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”

He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.

For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.

To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.

In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).

Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.

The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
 

Study stopped early

The aim of the study was to demonstrate noninferiority with the chemotherapy approach.

However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.

The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).

The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).

The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).

A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).

“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.

In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.

Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).

Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.

Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.

Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.

“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”

Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.

SOURCE: EHA Congress. Abstract S102.

A version of this article originally appeared on Medscape.com.

Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.

The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.

“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.

The findings in favor of total body irradiation were pronounced enough that the study was halted early by a safety committee, she added.

Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.

Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”

Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.

“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.

“I think it is very important to better identify those who really need total body irradiation in the future,” she added.

In an interview, Dr. Izraeli agreed.

“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”

He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.

For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.

To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.

In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).

Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.

The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
 

Study stopped early

The aim of the study was to demonstrate noninferiority with the chemotherapy approach.

However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.

The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).

The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).

The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).

A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).

“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.

In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.

Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).

Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.

Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.

Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.

“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”

Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.

SOURCE: EHA Congress. Abstract S102.

A version of this article originally appeared on Medscape.com.

Hematopoietic stem cell transplantation (HSCT) may offer the chance of a cure for patients with leukemia and other blood cancers, but the process of preparing the body to receive such a transplant can be brutal, involving whole body irradiation as well as chemotherapy conditioning. New results show that both steps are needed: a trial that omitted whole body irradiation in young patients with acute lymphoblastic leukemia (ALL) was stopped early because of significantly poorer outcomes.

The multicenter, global FORUM (For Omitting Radiation Under Majority Age) trial involved 75 centers in 17 countries between 2013 and 2018.

“Our study shows significantly better outcomes for total body irradiation compared to myeloablative chemo-conditioning arms, with no differences between the [two] chemo-conditioning groups,” concluded Christina Peters, MD, professor of pediatrics in the department of stem cell transplantation at St Anna Children’s Hospital in Vienna.

The findings in favor of total body irradiation were pronounced enough that the study was halted early by a safety committee, she added.

Dr. Peters presented the findings as part of the virtual annual congress of the European Hematology Association.

Describing the results as “sobering,” session comoderator Shai Izraeli, MD, director of the department of hematology-oncology at Schneider Children’s Medical Center, in Petah Tikva, Israel, said an online comment from the virtual meeting audience reflected the reaction to these unwelcome results: “So we are still stuck with total body irradiation?”

Dr. Peters said the good news is that the number of patients needing to undergo stem cell transplants is low, and with research advances, may hopefully drop even further.

“Only 10% of patients under the age of 18 nowadays undergo allogeneic HSCT, and perhaps in the future that will become even less if we are able to rescue some of the groups with other immunological measures such as CAR-T cells and antibodies,” she said.

“I think it is very important to better identify those who really need total body irradiation in the future,” she added.

In an interview, Dr. Izraeli agreed.

“The prognosis of children after bone marrow transplantation is excellent – the majority are cured from their leukemia,” he said. “And we have to remember that those who undergo bone marrow transplant have the worst leukemias.”

He pointed out that, in fact, contemporary chemotherapy alone is effective in the treatment of more than 90% of patients with ALL younger than aged 18.

For the 10% of patients who do not respond to chemotherapy alone and undergo allogeneic HSCT, about 50%-80% of pediatric patients who have resistant leukemia are cured. However, the total body irradiation used to prepare the body to receive the transplant is linked to potentially serious consequences later in life, including sterility, lung problems, growth retardation, and secondary cancer.

To determine if the irradiation component could be safely replaced with a chemotherapy-based conditioning approach, Dr. Peters and colleagues conducted the FORUM trial.

In total 413 patients undergoing HSCT were enrolled and randomized to pretransplant conditioning with total body irradiation and etoposide (n = 202) or a chemotherapy-only approach with fludarabine/thiotepa/busulfan (flu/thio/bu; n = 99) or fludarabine/thiotepa/treosulfan (treo; n = 93).

Most patients (72%) had B-cell precursor ALL and 23% had T-cell ALL. Just over half (54%) were transplanted in first complete remission (CR1), 40% in CR2, and 4% in CR3.

The source of stem cells was bone marrow for most patients (82%); peripheral blood stem cell for 12%, and cord blood for 4%.
 

Study stopped early

The aim of the study was to demonstrate noninferiority with the chemotherapy approach.

However, the significantly inferior outcome observed in the chemotherapy-only group led to randomization being halted in March 2019.

The 2-year overall survival in the intent-to-treat (ITT) analysis, with a mean observation time of 2.1 years, was 0.75 ± 0.04 for chemo-conditioning versus 0.91 ± 0.02 for total body irradiation/etoposide (ITT P < .001).

The ITT analysis showed relapses were significantly higher in the chemo-conditioning group (2-year cumulative incidence of relapse [CIR], 0.33) compared with the total body irradiation group (CIR, 0.12; P < .001).

The 2-year event-free survival (EFS) rate was also significantly higher in the total body irradiation group (0.86 vs 0.58; P < .001), and transplant-related mortality over 2 years was lower with total body irradiation (0.02 vs 0.09; P = .02).

A per-protocol analysis showed the 2-year overall survival to be the same in the two chemotherapy groups (both 0.77 ± 0.05) compared with 0.91 ± 0.02 in the total body irradiation group (P = .003).

“In this cohort [the 91% overall survival rate] may even be lower than contemporary intensive frontline therapy results that are achieved nowadays,” Dr. Peters said.

In looking at subgroups, there were no significant differences according to age group or cancer phenotype, while MLL rearrangement was associated with higher relapse incidence.

Remission status was found to notably influence EFS, dropping from 0.91 in CR1 patients with total body irradiation to 0.76 in CR2 patients. However, total body irradiation remained significantly higher compared with the chemo-conditioning groups in CR1 (P = .004) and CR2 (P < .001).

Transplant-related mortality was not significantly different between the total body irradiation and chemo-conditioning groups in the CR1 or CR2 groups (P = .09 and P = .18, respectively), despite the significant difference when remission status was not included.

Overall, “we tried to identify subgroups in which total body irradiation might be eliminated, however in all analyses, total body irradiation was better than chemo-conditioning in all arms,” Dr. Peters said.

Meanwhile, the findings underscore that even when patients cannot receive total body irradiation, the alternative chemo-conditioning therapy in fact shows favorable efficacy on its own, Dr. Izraeli said.

“The prognosis of the chemotherapy group is also quite remarkably good, although less than the total body irradiation arm. This means that if for some reason total body irradiation cannot be given, the chemotherapy is a very reasonable alternative.”

Dr. Peters has reported relationships with Amgen, Novartis, Pfizer, Medac, Jazz, and Neovii. Dr. Izraeli has reported no relevant financial relationships.

SOURCE: EHA Congress. Abstract S102.

A version of this article originally appeared on Medscape.com.