Boston Children’s Hospital tops annual ranking

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Boston Children’s Hospital is the country’s top hospital for children, according to U.S. New & World Report.

This marks the 3rd consecutive year and the fifth time in 6 years that Boston Children’s Hospital either has earned the honor on its own or been tied for the top spot. This year’s second-place finisher, Children’s Hospital of Philadelphia, was first in 2013-2014 and tied for first in 2014-2015 and 2012-2013.

The institutions in third and fourth place – Cincinnati Children’s Hospital Medical Center and Texas Children’s Hospital in Houston – remain the same as last year, but the fifth-place hospital, Johns Hopkins Children’s Center in Baltimore, was not even in the top 10 last year, U.S. News & World Report said in its 2017-2018 Best Children’s Hospitals rankings, which were released June 27.

Of the 187 facilities that qualified for inclusion this year, 113 submitted sufficient data to be considered in at least one of the 10 specialties that make up the rating: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology, and urology. In addition, a survey of individuals conducted to establish the hospitals’ reputations – generally worth about 15% of a hospital’s score in each specialty – was completed by 3,269 physicians.

Boston Children’s Hospital was ranked first in five of the ten specialties, Children’s Hospital of Philadelphia finished first in diabetes/endocrinology and pulmonology, Texas Children’s Hospital was first in cardiology/heart surgery, Children’s National Medical Center was first in neonatology, and St. Jude Children’s Research Hospital in Memphis topped the cancer ranking, U.S. News & World Report said.

The research organization, RTI International, conducted the physician survey and produced the methodology and national rankings under contract with U.S. News & World Report.

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Boston Children’s Hospital is the country’s top hospital for children, according to U.S. New & World Report.

This marks the 3rd consecutive year and the fifth time in 6 years that Boston Children’s Hospital either has earned the honor on its own or been tied for the top spot. This year’s second-place finisher, Children’s Hospital of Philadelphia, was first in 2013-2014 and tied for first in 2014-2015 and 2012-2013.

The institutions in third and fourth place – Cincinnati Children’s Hospital Medical Center and Texas Children’s Hospital in Houston – remain the same as last year, but the fifth-place hospital, Johns Hopkins Children’s Center in Baltimore, was not even in the top 10 last year, U.S. News & World Report said in its 2017-2018 Best Children’s Hospitals rankings, which were released June 27.

Of the 187 facilities that qualified for inclusion this year, 113 submitted sufficient data to be considered in at least one of the 10 specialties that make up the rating: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology, and urology. In addition, a survey of individuals conducted to establish the hospitals’ reputations – generally worth about 15% of a hospital’s score in each specialty – was completed by 3,269 physicians.

Boston Children’s Hospital was ranked first in five of the ten specialties, Children’s Hospital of Philadelphia finished first in diabetes/endocrinology and pulmonology, Texas Children’s Hospital was first in cardiology/heart surgery, Children’s National Medical Center was first in neonatology, and St. Jude Children’s Research Hospital in Memphis topped the cancer ranking, U.S. News & World Report said.

The research organization, RTI International, conducted the physician survey and produced the methodology and national rankings under contract with U.S. News & World Report.

 

Boston Children’s Hospital is the country’s top hospital for children, according to U.S. New & World Report.

This marks the 3rd consecutive year and the fifth time in 6 years that Boston Children’s Hospital either has earned the honor on its own or been tied for the top spot. This year’s second-place finisher, Children’s Hospital of Philadelphia, was first in 2013-2014 and tied for first in 2014-2015 and 2012-2013.

The institutions in third and fourth place – Cincinnati Children’s Hospital Medical Center and Texas Children’s Hospital in Houston – remain the same as last year, but the fifth-place hospital, Johns Hopkins Children’s Center in Baltimore, was not even in the top 10 last year, U.S. News & World Report said in its 2017-2018 Best Children’s Hospitals rankings, which were released June 27.

Of the 187 facilities that qualified for inclusion this year, 113 submitted sufficient data to be considered in at least one of the 10 specialties that make up the rating: cancer, cardiology and heart surgery, diabetes and endocrinology, gastroenterology and gastrointestinal surgery, neonatology, nephrology, neurology and neurosurgery, orthopedics, pulmonology, and urology. In addition, a survey of individuals conducted to establish the hospitals’ reputations – generally worth about 15% of a hospital’s score in each specialty – was completed by 3,269 physicians.

Boston Children’s Hospital was ranked first in five of the ten specialties, Children’s Hospital of Philadelphia finished first in diabetes/endocrinology and pulmonology, Texas Children’s Hospital was first in cardiology/heart surgery, Children’s National Medical Center was first in neonatology, and St. Jude Children’s Research Hospital in Memphis topped the cancer ranking, U.S. News & World Report said.

The research organization, RTI International, conducted the physician survey and produced the methodology and national rankings under contract with U.S. News & World Report.

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Clearer instructions linked to fewer medication dosing errors

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In nine pediatric dosing trials, more than 80% of parents made more than one medication dosing error, according to a study by H. Shonna Yin, MD, and associates. Misunderstandings about how to accurately choose the right dosing tools as well as confusion related to units of measure contribute to most errors. Matching dosing tools more closely with prescribed dose volumes, as well as using pictograms, can greatly reduce the number of pediatric medication errors, the researchers noted.

The study shows that 83.5% of parents made at least one dosing error (overdosing was present in 12.1% of errors), and 29.3% of parents made at least one large error in administering their children’s medicine. Parents who received text-only instructions or milliliter/teaspoon labels made more large errors. The biggest influence on errors resulted from providing tools more closely matched to the recommended dose measurements.

The researchers conducted a randomized controlled experiment in three pediatric clinics. Each site’s institutional review board approved the study. An average of 491 parents of children older than 8 years were randomly assigned to one of four groups, and given labels and dosing tools that varied in label instruction format and units. Each parent measured nine doses of liquid medicine in a random order, using three different tools.

Parents in group 1 received text and pictogram dosing instructions with milliliter-only labels and tools. They had decreased odds of making a dosing error compared with parents who received milliliter/teaspoon labels and tools without pictographic instructions in groups 2 and 4, and had lower odds of making large dosing errors compared with group 3, whose participants received text-only instructions (Pediatrics. 2017 June 27. doi: 10.1542/peds.2016-3237).

“Our findings support the use of a specific algorithm to help health care providers and pharmacists determine which dosing tool is most optimal to provide to parents,” said Dr. Yin. “We found that pictograms were associated with statistically significant reductions in large overdosing errors, with a trend for reduction in any error.”

No financial disclosures or conflicts of interest were reported.

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In nine pediatric dosing trials, more than 80% of parents made more than one medication dosing error, according to a study by H. Shonna Yin, MD, and associates. Misunderstandings about how to accurately choose the right dosing tools as well as confusion related to units of measure contribute to most errors. Matching dosing tools more closely with prescribed dose volumes, as well as using pictograms, can greatly reduce the number of pediatric medication errors, the researchers noted.

The study shows that 83.5% of parents made at least one dosing error (overdosing was present in 12.1% of errors), and 29.3% of parents made at least one large error in administering their children’s medicine. Parents who received text-only instructions or milliliter/teaspoon labels made more large errors. The biggest influence on errors resulted from providing tools more closely matched to the recommended dose measurements.

The researchers conducted a randomized controlled experiment in three pediatric clinics. Each site’s institutional review board approved the study. An average of 491 parents of children older than 8 years were randomly assigned to one of four groups, and given labels and dosing tools that varied in label instruction format and units. Each parent measured nine doses of liquid medicine in a random order, using three different tools.

Parents in group 1 received text and pictogram dosing instructions with milliliter-only labels and tools. They had decreased odds of making a dosing error compared with parents who received milliliter/teaspoon labels and tools without pictographic instructions in groups 2 and 4, and had lower odds of making large dosing errors compared with group 3, whose participants received text-only instructions (Pediatrics. 2017 June 27. doi: 10.1542/peds.2016-3237).

“Our findings support the use of a specific algorithm to help health care providers and pharmacists determine which dosing tool is most optimal to provide to parents,” said Dr. Yin. “We found that pictograms were associated with statistically significant reductions in large overdosing errors, with a trend for reduction in any error.”

No financial disclosures or conflicts of interest were reported.

 

In nine pediatric dosing trials, more than 80% of parents made more than one medication dosing error, according to a study by H. Shonna Yin, MD, and associates. Misunderstandings about how to accurately choose the right dosing tools as well as confusion related to units of measure contribute to most errors. Matching dosing tools more closely with prescribed dose volumes, as well as using pictograms, can greatly reduce the number of pediatric medication errors, the researchers noted.

The study shows that 83.5% of parents made at least one dosing error (overdosing was present in 12.1% of errors), and 29.3% of parents made at least one large error in administering their children’s medicine. Parents who received text-only instructions or milliliter/teaspoon labels made more large errors. The biggest influence on errors resulted from providing tools more closely matched to the recommended dose measurements.

The researchers conducted a randomized controlled experiment in three pediatric clinics. Each site’s institutional review board approved the study. An average of 491 parents of children older than 8 years were randomly assigned to one of four groups, and given labels and dosing tools that varied in label instruction format and units. Each parent measured nine doses of liquid medicine in a random order, using three different tools.

Parents in group 1 received text and pictogram dosing instructions with milliliter-only labels and tools. They had decreased odds of making a dosing error compared with parents who received milliliter/teaspoon labels and tools without pictographic instructions in groups 2 and 4, and had lower odds of making large dosing errors compared with group 3, whose participants received text-only instructions (Pediatrics. 2017 June 27. doi: 10.1542/peds.2016-3237).

“Our findings support the use of a specific algorithm to help health care providers and pharmacists determine which dosing tool is most optimal to provide to parents,” said Dr. Yin. “We found that pictograms were associated with statistically significant reductions in large overdosing errors, with a trend for reduction in any error.”

No financial disclosures or conflicts of interest were reported.

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Key clinical point: Matching dosing tools with prescribed dose volumes reduces pediatric medication errors.

Major finding: In nine dosing trials, 83.5% of parents made more than one medication dosing error, mainly overdosing.

Data source: A randomized controlled study. Recruitment took place in pediatric outpatient clinics in New York, California, and Georgia. Each site’s institutional review board approved the study.

Disclosures: The National Institutes of Health/National Institute of Child Health and Human Development funded the study. The authors declared no conflict of interest.

CRPM may be promising predictive biomarker for knee osteoarthritis

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Fri, 01/18/2019 - 16:52

 

Serum matrix metalloproteinase-degraded C-reactive protein, or CRPM, may be the answer to two major unmet needs in the effort to develop the first disease-modifying treatments for osteoarthritis, Anne-Christine Bay-Jensen, PhD, said at the World Congress on Osteoarthritis.

Dr. Anne C. Bay-Jensen
Dr. Anne C. Bay-Jensen
To efficiently test candidate disease-modifying osteoarthritis therapies in clinical trials, researchers desperately need two things: a biomarker that’s predictive of individuals at high risk of developing osteoarthritis in the near term to test the efficacy of potential preventive agents; and a means of identifying particular osteoarthritis phenotypes so that a potential treatment with a specific mechanism of action can be matched to the most appropriate patient subgroup.
That way, investigators maximize the likelihood of obtaining a positive outcome undiluted by giving the therapy to the wrong patients.

CRPM shows preliminary evidence of passing muster on both counts, according to Dr. Bay-Jensen, head of rheumatology at Nordic Bioscience in Herløv, Denmark.

The Danish researcher introduced herself to the Las Vegas audience by announcing, “My purpose in life is to develop biomarkers for identifying phenotypes in osteoarthritis.”

Indeed, she has been a pioneer in investigating the clinical utility of CRPM, a degradation fragment of C-reactive protein that is produced in the joint and thus reflects joint-specific tissue inflammation. Unlike C-reactive protein, which is an acute phase reactant, CRPM reflects chronic inflammation, she explained at the meeting sponsored by the Osteoarthritis Research Society International.

Her early work with CRPM explored its use as a biomarker in rheumatoid arthritis (RA) patients. She demonstrated, for example, in a secondary analysis of the phase III, double-blind, placebo-controlled LITHE trial that an 11% reduction in CRPM at week 4 of treatment with tocilizumab (Actemra) plus methotrexate was associated with a fourfold increased likelihood of a clinical response at week 16. That finding indicates that utilizing CRPM as an early predictor of tocilizumab efficacy promotes a more targeted, cost-effective, and personalized use of the biologic agent.

At OARSI 2017, Dr. Bay-Jensen presented evidence that even though the mean serum CRPM is significantly higher in patients with RA than in those with knee osteoarthritis (KOA), one-third or more of KOA patients have levels of joint tissue inflammation comparable to that seen in RA. That patient subset with a highly inflammatory KOA phenotype would be the logical focus of future clinical trials of agents having potent anti-inflammatory effects, rather than potential therapies with bone- or cartilage-modifying effects.

The data came from a biomarker study of 113 patients with early RA, as well as from two Nordic Bioscience–sponsored phase III randomized, multicenter, placebo-controlled clinical trials of oral salmon calcitonin in a total of 2,306 patients with knee osteoarthritis, both of which proved negative (Osteoarthritis Cartilage. 2015 Apr;23[4]:532-43). The mean baseline CRPM in the early RA patients was 17.1 ng/mL, compared with 8.5 ng/mL in the KOA patients. However, 31% of KOA patients in one phase III oral calcitonin trial and 41% in the other had a baseline serum CRPM greater than 9 ng/mL, a level that overlapped with 75% of the RA patients.

A related substudy of the oral calcitonin trials examined CRPM as a predictive biomarker. It included 153 knees without OA at baseline, 50 of which developed radiographic evidence of KOA, as evidenced by a Kellgren-Lawrence grade of 2 or 3 during 2 years of prospective follow-up. A serum CRPM of 9 ng/mL or more at baseline was associated with a 4.6-fold increased likelihood of incident KOA during follow-up.

Nordic Bioscience, Dr. Bay-Jensen’s employer, markets numerous proprietary biomarker assays, including one for CRPM.

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Serum matrix metalloproteinase-degraded C-reactive protein, or CRPM, may be the answer to two major unmet needs in the effort to develop the first disease-modifying treatments for osteoarthritis, Anne-Christine Bay-Jensen, PhD, said at the World Congress on Osteoarthritis.

Dr. Anne C. Bay-Jensen
Dr. Anne C. Bay-Jensen
To efficiently test candidate disease-modifying osteoarthritis therapies in clinical trials, researchers desperately need two things: a biomarker that’s predictive of individuals at high risk of developing osteoarthritis in the near term to test the efficacy of potential preventive agents; and a means of identifying particular osteoarthritis phenotypes so that a potential treatment with a specific mechanism of action can be matched to the most appropriate patient subgroup.
That way, investigators maximize the likelihood of obtaining a positive outcome undiluted by giving the therapy to the wrong patients.

CRPM shows preliminary evidence of passing muster on both counts, according to Dr. Bay-Jensen, head of rheumatology at Nordic Bioscience in Herløv, Denmark.

The Danish researcher introduced herself to the Las Vegas audience by announcing, “My purpose in life is to develop biomarkers for identifying phenotypes in osteoarthritis.”

Indeed, she has been a pioneer in investigating the clinical utility of CRPM, a degradation fragment of C-reactive protein that is produced in the joint and thus reflects joint-specific tissue inflammation. Unlike C-reactive protein, which is an acute phase reactant, CRPM reflects chronic inflammation, she explained at the meeting sponsored by the Osteoarthritis Research Society International.

Her early work with CRPM explored its use as a biomarker in rheumatoid arthritis (RA) patients. She demonstrated, for example, in a secondary analysis of the phase III, double-blind, placebo-controlled LITHE trial that an 11% reduction in CRPM at week 4 of treatment with tocilizumab (Actemra) plus methotrexate was associated with a fourfold increased likelihood of a clinical response at week 16. That finding indicates that utilizing CRPM as an early predictor of tocilizumab efficacy promotes a more targeted, cost-effective, and personalized use of the biologic agent.

At OARSI 2017, Dr. Bay-Jensen presented evidence that even though the mean serum CRPM is significantly higher in patients with RA than in those with knee osteoarthritis (KOA), one-third or more of KOA patients have levels of joint tissue inflammation comparable to that seen in RA. That patient subset with a highly inflammatory KOA phenotype would be the logical focus of future clinical trials of agents having potent anti-inflammatory effects, rather than potential therapies with bone- or cartilage-modifying effects.

The data came from a biomarker study of 113 patients with early RA, as well as from two Nordic Bioscience–sponsored phase III randomized, multicenter, placebo-controlled clinical trials of oral salmon calcitonin in a total of 2,306 patients with knee osteoarthritis, both of which proved negative (Osteoarthritis Cartilage. 2015 Apr;23[4]:532-43). The mean baseline CRPM in the early RA patients was 17.1 ng/mL, compared with 8.5 ng/mL in the KOA patients. However, 31% of KOA patients in one phase III oral calcitonin trial and 41% in the other had a baseline serum CRPM greater than 9 ng/mL, a level that overlapped with 75% of the RA patients.

A related substudy of the oral calcitonin trials examined CRPM as a predictive biomarker. It included 153 knees without OA at baseline, 50 of which developed radiographic evidence of KOA, as evidenced by a Kellgren-Lawrence grade of 2 or 3 during 2 years of prospective follow-up. A serum CRPM of 9 ng/mL or more at baseline was associated with a 4.6-fold increased likelihood of incident KOA during follow-up.

Nordic Bioscience, Dr. Bay-Jensen’s employer, markets numerous proprietary biomarker assays, including one for CRPM.

 

Serum matrix metalloproteinase-degraded C-reactive protein, or CRPM, may be the answer to two major unmet needs in the effort to develop the first disease-modifying treatments for osteoarthritis, Anne-Christine Bay-Jensen, PhD, said at the World Congress on Osteoarthritis.

Dr. Anne C. Bay-Jensen
Dr. Anne C. Bay-Jensen
To efficiently test candidate disease-modifying osteoarthritis therapies in clinical trials, researchers desperately need two things: a biomarker that’s predictive of individuals at high risk of developing osteoarthritis in the near term to test the efficacy of potential preventive agents; and a means of identifying particular osteoarthritis phenotypes so that a potential treatment with a specific mechanism of action can be matched to the most appropriate patient subgroup.
That way, investigators maximize the likelihood of obtaining a positive outcome undiluted by giving the therapy to the wrong patients.

CRPM shows preliminary evidence of passing muster on both counts, according to Dr. Bay-Jensen, head of rheumatology at Nordic Bioscience in Herløv, Denmark.

The Danish researcher introduced herself to the Las Vegas audience by announcing, “My purpose in life is to develop biomarkers for identifying phenotypes in osteoarthritis.”

Indeed, she has been a pioneer in investigating the clinical utility of CRPM, a degradation fragment of C-reactive protein that is produced in the joint and thus reflects joint-specific tissue inflammation. Unlike C-reactive protein, which is an acute phase reactant, CRPM reflects chronic inflammation, she explained at the meeting sponsored by the Osteoarthritis Research Society International.

Her early work with CRPM explored its use as a biomarker in rheumatoid arthritis (RA) patients. She demonstrated, for example, in a secondary analysis of the phase III, double-blind, placebo-controlled LITHE trial that an 11% reduction in CRPM at week 4 of treatment with tocilizumab (Actemra) plus methotrexate was associated with a fourfold increased likelihood of a clinical response at week 16. That finding indicates that utilizing CRPM as an early predictor of tocilizumab efficacy promotes a more targeted, cost-effective, and personalized use of the biologic agent.

At OARSI 2017, Dr. Bay-Jensen presented evidence that even though the mean serum CRPM is significantly higher in patients with RA than in those with knee osteoarthritis (KOA), one-third or more of KOA patients have levels of joint tissue inflammation comparable to that seen in RA. That patient subset with a highly inflammatory KOA phenotype would be the logical focus of future clinical trials of agents having potent anti-inflammatory effects, rather than potential therapies with bone- or cartilage-modifying effects.

The data came from a biomarker study of 113 patients with early RA, as well as from two Nordic Bioscience–sponsored phase III randomized, multicenter, placebo-controlled clinical trials of oral salmon calcitonin in a total of 2,306 patients with knee osteoarthritis, both of which proved negative (Osteoarthritis Cartilage. 2015 Apr;23[4]:532-43). The mean baseline CRPM in the early RA patients was 17.1 ng/mL, compared with 8.5 ng/mL in the KOA patients. However, 31% of KOA patients in one phase III oral calcitonin trial and 41% in the other had a baseline serum CRPM greater than 9 ng/mL, a level that overlapped with 75% of the RA patients.

A related substudy of the oral calcitonin trials examined CRPM as a predictive biomarker. It included 153 knees without OA at baseline, 50 of which developed radiographic evidence of KOA, as evidenced by a Kellgren-Lawrence grade of 2 or 3 during 2 years of prospective follow-up. A serum CRPM of 9 ng/mL or more at baseline was associated with a 4.6-fold increased likelihood of incident KOA during follow-up.

Nordic Bioscience, Dr. Bay-Jensen’s employer, markets numerous proprietary biomarker assays, including one for CRPM.

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Very-low-volume vascular surgery practice linked to worse outcomes

Choosing volume thresholds
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Mon, 01/07/2019 - 12:56

 

The very-low-volume practice of surgeons performing no more than one open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA) per year has persisted in New York State and was associated with worse postoperative outcomes and longer lengths of stay in a cohort study of statewide hospital data.

The study examined inpatient data on elective OARs and CEAs performed from 2000 to 2014 in every hospital in the state.

While the numbers and proportions of very-low-volume surgeons decreased (44.6%-23% for OAR and 35.2%-18.1% for CEA) and the number of procedures performed by these surgeons also decreased (QAR, 346-47; CEA, 395-90), the data are “concerning” and elucidate the “persistence” of very-low-volume practice in open vascular surgery, said Jialin Mao, MD, of Cornell University, New York, and associates (JAMA Surg. doi: 10:1001/jamasurg.2017.1100).

Very-low-volume surgeons were significantly less likely to be vascular surgeons, compared with higher-volume surgeons for both OAR (23.9% vs. 63.9%) and CEA (14.6% vs. 51.7%), they reported.

Compared with patients treated by higher-volume surgeons, those whose OAR was performed by very-low-volume surgeons had a twofold higher risk of postoperative death (6.7% vs. 3.5%) after adjusting for patient risk factors, surgeon specialty, and facility characteristics. Patients of very-low-volume surgeons also had significantly higher odds of sepsis or shock (odds ratio, 1.45), prolonged length of stay (OR, 1.37) and 30-day readmission (OR, 1.19), although the latter was not significant.

Similarly, patients whose CEA was performed by very-low-volume surgeons had a significant 1.8-fold higher odds of experiencing postoperative acute myocardial infarction (1.5% vs. 0.5%) and stroke (3.5% vs. 2.1%). They also were significantly more likely to have 30-day readmission (OR, 1.30).

With both procedures, patients treated by very-low-volume surgeons tended to be younger and healthier (less likely to have two or more comorbidities). They also were more likely to be nonwhite or insured by Medicaid.

“It is reasonable to speculate,” the researchers wrote, “that those treated by very-low-volume surgeons were more likely to be socioeconomically disadvantaged.”

Notably, 30% of the very-low-volume practice occurred in New York City, “where accessibility to high-volume practitioners should generally be higher,” they said.

The findings “indicate the need to eliminate this type of practice, to restrict the practice of these very-low-volume surgeons or to force referrals to higher-volume and specialized surgeons, and to improve disparity in access to high-quality care for all patients,” they said.

The study was funded in part by the U.S. Food and Drug Administration. The researchers reported having no relevant conflicts of interest.

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The delineation of a threshold number of cases of OAR and CEA below which surgeons should not be credentialed remains unclear, despite much discussion of the volume-outcome relationship in vascular surgery.

In the current endovascular era, OAR in particular has become increasingly less frequent, with a dramatic effect on trainee experiences. It is often proposed that these cases be limited to high-volume surgeons. Some are concerned, however, that this action will leave rural surgeons unprepared to deal with ruptured abdominal aortic aneurysm and will force patients to travel long distances.

Dr. Marc Schermerhorn
Researchers have shown that transferring patients from low-volume to high-volume centers can improve outcomes and save lives. But what low volume is too low? Our research on the effect of surgeon volume on mortality after OAR suggests that a threshold of eight or fewer cases may be optimal (J Vasc Surg. 2017;65[3]:626-34). However, it may be more politically acceptable – and therefore more feasible – to work with a threshold that’s much lower. The data that this study presents may be a reasonable place to start.

Sarah E. Deery, MD, and Marc L. Schermerhorn, MD, are in the division of vascular and endovascular surgery at Beth Israel Deaconess Medical Center in Boston. These remarks are adapted from an editorial accompanying the study. They reported having no disclosures.

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The delineation of a threshold number of cases of OAR and CEA below which surgeons should not be credentialed remains unclear, despite much discussion of the volume-outcome relationship in vascular surgery.

In the current endovascular era, OAR in particular has become increasingly less frequent, with a dramatic effect on trainee experiences. It is often proposed that these cases be limited to high-volume surgeons. Some are concerned, however, that this action will leave rural surgeons unprepared to deal with ruptured abdominal aortic aneurysm and will force patients to travel long distances.

Dr. Marc Schermerhorn
Researchers have shown that transferring patients from low-volume to high-volume centers can improve outcomes and save lives. But what low volume is too low? Our research on the effect of surgeon volume on mortality after OAR suggests that a threshold of eight or fewer cases may be optimal (J Vasc Surg. 2017;65[3]:626-34). However, it may be more politically acceptable – and therefore more feasible – to work with a threshold that’s much lower. The data that this study presents may be a reasonable place to start.

Sarah E. Deery, MD, and Marc L. Schermerhorn, MD, are in the division of vascular and endovascular surgery at Beth Israel Deaconess Medical Center in Boston. These remarks are adapted from an editorial accompanying the study. They reported having no disclosures.

Body

 

The delineation of a threshold number of cases of OAR and CEA below which surgeons should not be credentialed remains unclear, despite much discussion of the volume-outcome relationship in vascular surgery.

In the current endovascular era, OAR in particular has become increasingly less frequent, with a dramatic effect on trainee experiences. It is often proposed that these cases be limited to high-volume surgeons. Some are concerned, however, that this action will leave rural surgeons unprepared to deal with ruptured abdominal aortic aneurysm and will force patients to travel long distances.

Dr. Marc Schermerhorn
Researchers have shown that transferring patients from low-volume to high-volume centers can improve outcomes and save lives. But what low volume is too low? Our research on the effect of surgeon volume on mortality after OAR suggests that a threshold of eight or fewer cases may be optimal (J Vasc Surg. 2017;65[3]:626-34). However, it may be more politically acceptable – and therefore more feasible – to work with a threshold that’s much lower. The data that this study presents may be a reasonable place to start.

Sarah E. Deery, MD, and Marc L. Schermerhorn, MD, are in the division of vascular and endovascular surgery at Beth Israel Deaconess Medical Center in Boston. These remarks are adapted from an editorial accompanying the study. They reported having no disclosures.

Title
Choosing volume thresholds
Choosing volume thresholds

 

The very-low-volume practice of surgeons performing no more than one open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA) per year has persisted in New York State and was associated with worse postoperative outcomes and longer lengths of stay in a cohort study of statewide hospital data.

The study examined inpatient data on elective OARs and CEAs performed from 2000 to 2014 in every hospital in the state.

While the numbers and proportions of very-low-volume surgeons decreased (44.6%-23% for OAR and 35.2%-18.1% for CEA) and the number of procedures performed by these surgeons also decreased (QAR, 346-47; CEA, 395-90), the data are “concerning” and elucidate the “persistence” of very-low-volume practice in open vascular surgery, said Jialin Mao, MD, of Cornell University, New York, and associates (JAMA Surg. doi: 10:1001/jamasurg.2017.1100).

Very-low-volume surgeons were significantly less likely to be vascular surgeons, compared with higher-volume surgeons for both OAR (23.9% vs. 63.9%) and CEA (14.6% vs. 51.7%), they reported.

Compared with patients treated by higher-volume surgeons, those whose OAR was performed by very-low-volume surgeons had a twofold higher risk of postoperative death (6.7% vs. 3.5%) after adjusting for patient risk factors, surgeon specialty, and facility characteristics. Patients of very-low-volume surgeons also had significantly higher odds of sepsis or shock (odds ratio, 1.45), prolonged length of stay (OR, 1.37) and 30-day readmission (OR, 1.19), although the latter was not significant.

Similarly, patients whose CEA was performed by very-low-volume surgeons had a significant 1.8-fold higher odds of experiencing postoperative acute myocardial infarction (1.5% vs. 0.5%) and stroke (3.5% vs. 2.1%). They also were significantly more likely to have 30-day readmission (OR, 1.30).

With both procedures, patients treated by very-low-volume surgeons tended to be younger and healthier (less likely to have two or more comorbidities). They also were more likely to be nonwhite or insured by Medicaid.

“It is reasonable to speculate,” the researchers wrote, “that those treated by very-low-volume surgeons were more likely to be socioeconomically disadvantaged.”

Notably, 30% of the very-low-volume practice occurred in New York City, “where accessibility to high-volume practitioners should generally be higher,” they said.

The findings “indicate the need to eliminate this type of practice, to restrict the practice of these very-low-volume surgeons or to force referrals to higher-volume and specialized surgeons, and to improve disparity in access to high-quality care for all patients,” they said.

The study was funded in part by the U.S. Food and Drug Administration. The researchers reported having no relevant conflicts of interest.

 

The very-low-volume practice of surgeons performing no more than one open abdominal aortic aneurysm repair (OAR) or carotid endarterectomy (CEA) per year has persisted in New York State and was associated with worse postoperative outcomes and longer lengths of stay in a cohort study of statewide hospital data.

The study examined inpatient data on elective OARs and CEAs performed from 2000 to 2014 in every hospital in the state.

While the numbers and proportions of very-low-volume surgeons decreased (44.6%-23% for OAR and 35.2%-18.1% for CEA) and the number of procedures performed by these surgeons also decreased (QAR, 346-47; CEA, 395-90), the data are “concerning” and elucidate the “persistence” of very-low-volume practice in open vascular surgery, said Jialin Mao, MD, of Cornell University, New York, and associates (JAMA Surg. doi: 10:1001/jamasurg.2017.1100).

Very-low-volume surgeons were significantly less likely to be vascular surgeons, compared with higher-volume surgeons for both OAR (23.9% vs. 63.9%) and CEA (14.6% vs. 51.7%), they reported.

Compared with patients treated by higher-volume surgeons, those whose OAR was performed by very-low-volume surgeons had a twofold higher risk of postoperative death (6.7% vs. 3.5%) after adjusting for patient risk factors, surgeon specialty, and facility characteristics. Patients of very-low-volume surgeons also had significantly higher odds of sepsis or shock (odds ratio, 1.45), prolonged length of stay (OR, 1.37) and 30-day readmission (OR, 1.19), although the latter was not significant.

Similarly, patients whose CEA was performed by very-low-volume surgeons had a significant 1.8-fold higher odds of experiencing postoperative acute myocardial infarction (1.5% vs. 0.5%) and stroke (3.5% vs. 2.1%). They also were significantly more likely to have 30-day readmission (OR, 1.30).

With both procedures, patients treated by very-low-volume surgeons tended to be younger and healthier (less likely to have two or more comorbidities). They also were more likely to be nonwhite or insured by Medicaid.

“It is reasonable to speculate,” the researchers wrote, “that those treated by very-low-volume surgeons were more likely to be socioeconomically disadvantaged.”

Notably, 30% of the very-low-volume practice occurred in New York City, “where accessibility to high-volume practitioners should generally be higher,” they said.

The findings “indicate the need to eliminate this type of practice, to restrict the practice of these very-low-volume surgeons or to force referrals to higher-volume and specialized surgeons, and to improve disparity in access to high-quality care for all patients,” they said.

The study was funded in part by the U.S. Food and Drug Administration. The researchers reported having no relevant conflicts of interest.

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Key clinical point: The very-low-volume practice of open abdominal aortic aneurysm repair and carotid endarterectomy (one or fewer annual procedures) is associated with worse postoperative outcomes and greater length of stay.

Major finding: Patients whose procedure was performed by very-low-volume surgeons had a twofold higher risk of postoperative death after OAR or 1.8-fold higher odds of experiencing postoperative acute myocardial infarction or stroke after CEA.

Data source: The study was funded in part by the U.S. Food and Drug Administration.

Disclosures: The researchers reported having no relevant conflicts of interest.

MV disease in children requires modified strategies

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Tue, 02/14/2023 - 13:05

 

– Repairing mitral valves in pediatric patients must overcome two issues: the wide variability in their anatomy and their growth. Using strategies and techniques common in adult mitral surgery can accomplish good mitral valve function in children, but some techniques in children differ, like using combined resorbable material with autologous tissue or transferring native chords instead of placing artificial chords to a malfunctioning leaflet.

Pedro del Nido, MD, of Boston Children’s Hospital, said the spectrum of mitral valve pathology in children goes from congenital mitral stenosis with a thick annulus with leaflet immobility to leaflet hypermobility that involves anterior leaflet prolapse and can involve a cleft that causes regurgitation. Dr. del Nido explained his surgical approaches for mitral valve disease in children at the 2017 Mitral Conclave, sponsored by the American Association of Thoracic Surgery.

Dr. Pedro del Nido
“You have to consider mitral valve disease in kids from the top to the bottom,” Dr. del Nido said. “So think about it from the annulus where there’s a supra-annular ring of tissue that’s restricting the mobility of the leaflets, as well as clefts and holes. The more common pathology that we see with stenosis is subvalvar pathology – fusion of the leaflets, fusion of the leaflet tips of the papillaries to absence of chords.”

Accessing the mitral valve in children requires a different approach than in adults, Dr. del Nido said. “Going through the left atrium is generally difficult, so we often enter through a trans-septal incision,” he said. “The main reason for that is because the tricuspid valve is often associated with the mitral valve problem and this gives us the most direct exposure.”

Once the surgeon gains exposure, the surgical analysis for a diseased adult or child valve is almost identical, with the exception that adult disease is acquired whereas childhood disease tends to be congenital, Dr. del Nido said. “In the congenital patient, we often find fibroelastic tissue that the child is born with,” he said. “We see this in neonates and young infants. It thickens over time; it doesn’t often calcify, but it does often restrict the leaflets and it tends to fuse the chords, so in essence you have direct attachments of the leaflets to the papillaries.”

He explained that this pathology requires an approach similar to that for rheumatic mitral disease in adults. “Start splitting the commissures and start resecting the tissue off the chords creating fenestrations in order to improve the inflow.” Dr. del Nido added, “If you don’t do this, the child will always have a gradient, and if you think about an adult having problems and symptoms with a gradient, think about a 10-year-old running around trying to do athletics; it’s impossible.”

Dysfunctional chords also require a somewhat different approach in children than they require in adults. “We find elongation of the chords and the anterior support structure is abnormal; the secondary chords are totally intact,” Dr. del Nido said. When confronting a torn-edge chord, resection is often an option in adults, but is uncommon in children. “We don’t usually have very much leaflet tissue,” he said. Artificial chords do not accommodate growth.

“We tend to use native tissue,” said Dr. del Nido. “You can transfer the strut chord; you can transfer the secondary chord in order to achieve support for the edge of that prolapsed leaflet.”

Leaflet problems are probably the biggest single source of recurrence in children, Dr. del Nido said. A cleft on the anterior leaflet can be particularly vexing. For example, cleft edges attached to the septum can prevent the valve leaflet from coaptation with the posterior leaflet. “If you don’t recognize that on 3-D echocardiography, you’re going to have a problem; that leaflet will never create the coaptation surface that you want,” he said.

The solution may lie underneath the leaflet. Said Dr. del Nido, “We tend to want to close a cleft, and, yes, that will get you relief of regurgitation in the central portion, but if you end up with immobility of that leaflet, then look underneath. Most often there are very abnormal attachments to the edges of that cleft to the septum. You have to get rid of that; if you don’t resect all that, you’ll never have a leaflet that truly floats up to coapt against the posterior leaflet.”

Annular dilation in children can also challenge a cardiothoracic surgeon’s skill.

In rare cases, a suture commissuroplasty may correct the problem. Sometimes Dr. del Nido will use the DeVega suture annuloplasty – “even though it is very much user dependent; it’s very easy in pediatrics to create stenosis with the DeVega.” As an alternative, synthetic ring annuloplasties can confine valve growth and are rarely used.

Dr. del Nido’s preference is to use a hybrid approach of tissue and resorbable material. “The advantage of the resorbable material is that it will go away, but that’s also the problem with the resorbable material,” he said. “Once it does go away, there’s nothing there to support the annulus, so a combination of tissue and resorbable suture is probably the best answer.”

In posterior leaflet deficiency, a patch of pericardium posteriorly can augment the dysfunctional leaflet. You can also use pericardium as an annuloplasty ring. “You can use it circumferentially,” Dr. del Nido said. “It’s a soft ring; you can certainly use this material which is autologous; it does provide strength to the fibrous annulus; it does support that valve; and you do see growth.” He added that bovine pericardium is not ideal for this use.

Dr. del Nido reported no relevant financial relationships.
 

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– Repairing mitral valves in pediatric patients must overcome two issues: the wide variability in their anatomy and their growth. Using strategies and techniques common in adult mitral surgery can accomplish good mitral valve function in children, but some techniques in children differ, like using combined resorbable material with autologous tissue or transferring native chords instead of placing artificial chords to a malfunctioning leaflet.

Pedro del Nido, MD, of Boston Children’s Hospital, said the spectrum of mitral valve pathology in children goes from congenital mitral stenosis with a thick annulus with leaflet immobility to leaflet hypermobility that involves anterior leaflet prolapse and can involve a cleft that causes regurgitation. Dr. del Nido explained his surgical approaches for mitral valve disease in children at the 2017 Mitral Conclave, sponsored by the American Association of Thoracic Surgery.

Dr. Pedro del Nido
“You have to consider mitral valve disease in kids from the top to the bottom,” Dr. del Nido said. “So think about it from the annulus where there’s a supra-annular ring of tissue that’s restricting the mobility of the leaflets, as well as clefts and holes. The more common pathology that we see with stenosis is subvalvar pathology – fusion of the leaflets, fusion of the leaflet tips of the papillaries to absence of chords.”

Accessing the mitral valve in children requires a different approach than in adults, Dr. del Nido said. “Going through the left atrium is generally difficult, so we often enter through a trans-septal incision,” he said. “The main reason for that is because the tricuspid valve is often associated with the mitral valve problem and this gives us the most direct exposure.”

Once the surgeon gains exposure, the surgical analysis for a diseased adult or child valve is almost identical, with the exception that adult disease is acquired whereas childhood disease tends to be congenital, Dr. del Nido said. “In the congenital patient, we often find fibroelastic tissue that the child is born with,” he said. “We see this in neonates and young infants. It thickens over time; it doesn’t often calcify, but it does often restrict the leaflets and it tends to fuse the chords, so in essence you have direct attachments of the leaflets to the papillaries.”

He explained that this pathology requires an approach similar to that for rheumatic mitral disease in adults. “Start splitting the commissures and start resecting the tissue off the chords creating fenestrations in order to improve the inflow.” Dr. del Nido added, “If you don’t do this, the child will always have a gradient, and if you think about an adult having problems and symptoms with a gradient, think about a 10-year-old running around trying to do athletics; it’s impossible.”

Dysfunctional chords also require a somewhat different approach in children than they require in adults. “We find elongation of the chords and the anterior support structure is abnormal; the secondary chords are totally intact,” Dr. del Nido said. When confronting a torn-edge chord, resection is often an option in adults, but is uncommon in children. “We don’t usually have very much leaflet tissue,” he said. Artificial chords do not accommodate growth.

“We tend to use native tissue,” said Dr. del Nido. “You can transfer the strut chord; you can transfer the secondary chord in order to achieve support for the edge of that prolapsed leaflet.”

Leaflet problems are probably the biggest single source of recurrence in children, Dr. del Nido said. A cleft on the anterior leaflet can be particularly vexing. For example, cleft edges attached to the septum can prevent the valve leaflet from coaptation with the posterior leaflet. “If you don’t recognize that on 3-D echocardiography, you’re going to have a problem; that leaflet will never create the coaptation surface that you want,” he said.

The solution may lie underneath the leaflet. Said Dr. del Nido, “We tend to want to close a cleft, and, yes, that will get you relief of regurgitation in the central portion, but if you end up with immobility of that leaflet, then look underneath. Most often there are very abnormal attachments to the edges of that cleft to the septum. You have to get rid of that; if you don’t resect all that, you’ll never have a leaflet that truly floats up to coapt against the posterior leaflet.”

Annular dilation in children can also challenge a cardiothoracic surgeon’s skill.

In rare cases, a suture commissuroplasty may correct the problem. Sometimes Dr. del Nido will use the DeVega suture annuloplasty – “even though it is very much user dependent; it’s very easy in pediatrics to create stenosis with the DeVega.” As an alternative, synthetic ring annuloplasties can confine valve growth and are rarely used.

Dr. del Nido’s preference is to use a hybrid approach of tissue and resorbable material. “The advantage of the resorbable material is that it will go away, but that’s also the problem with the resorbable material,” he said. “Once it does go away, there’s nothing there to support the annulus, so a combination of tissue and resorbable suture is probably the best answer.”

In posterior leaflet deficiency, a patch of pericardium posteriorly can augment the dysfunctional leaflet. You can also use pericardium as an annuloplasty ring. “You can use it circumferentially,” Dr. del Nido said. “It’s a soft ring; you can certainly use this material which is autologous; it does provide strength to the fibrous annulus; it does support that valve; and you do see growth.” He added that bovine pericardium is not ideal for this use.

Dr. del Nido reported no relevant financial relationships.
 

 

– Repairing mitral valves in pediatric patients must overcome two issues: the wide variability in their anatomy and their growth. Using strategies and techniques common in adult mitral surgery can accomplish good mitral valve function in children, but some techniques in children differ, like using combined resorbable material with autologous tissue or transferring native chords instead of placing artificial chords to a malfunctioning leaflet.

Pedro del Nido, MD, of Boston Children’s Hospital, said the spectrum of mitral valve pathology in children goes from congenital mitral stenosis with a thick annulus with leaflet immobility to leaflet hypermobility that involves anterior leaflet prolapse and can involve a cleft that causes regurgitation. Dr. del Nido explained his surgical approaches for mitral valve disease in children at the 2017 Mitral Conclave, sponsored by the American Association of Thoracic Surgery.

Dr. Pedro del Nido
“You have to consider mitral valve disease in kids from the top to the bottom,” Dr. del Nido said. “So think about it from the annulus where there’s a supra-annular ring of tissue that’s restricting the mobility of the leaflets, as well as clefts and holes. The more common pathology that we see with stenosis is subvalvar pathology – fusion of the leaflets, fusion of the leaflet tips of the papillaries to absence of chords.”

Accessing the mitral valve in children requires a different approach than in adults, Dr. del Nido said. “Going through the left atrium is generally difficult, so we often enter through a trans-septal incision,” he said. “The main reason for that is because the tricuspid valve is often associated with the mitral valve problem and this gives us the most direct exposure.”

Once the surgeon gains exposure, the surgical analysis for a diseased adult or child valve is almost identical, with the exception that adult disease is acquired whereas childhood disease tends to be congenital, Dr. del Nido said. “In the congenital patient, we often find fibroelastic tissue that the child is born with,” he said. “We see this in neonates and young infants. It thickens over time; it doesn’t often calcify, but it does often restrict the leaflets and it tends to fuse the chords, so in essence you have direct attachments of the leaflets to the papillaries.”

He explained that this pathology requires an approach similar to that for rheumatic mitral disease in adults. “Start splitting the commissures and start resecting the tissue off the chords creating fenestrations in order to improve the inflow.” Dr. del Nido added, “If you don’t do this, the child will always have a gradient, and if you think about an adult having problems and symptoms with a gradient, think about a 10-year-old running around trying to do athletics; it’s impossible.”

Dysfunctional chords also require a somewhat different approach in children than they require in adults. “We find elongation of the chords and the anterior support structure is abnormal; the secondary chords are totally intact,” Dr. del Nido said. When confronting a torn-edge chord, resection is often an option in adults, but is uncommon in children. “We don’t usually have very much leaflet tissue,” he said. Artificial chords do not accommodate growth.

“We tend to use native tissue,” said Dr. del Nido. “You can transfer the strut chord; you can transfer the secondary chord in order to achieve support for the edge of that prolapsed leaflet.”

Leaflet problems are probably the biggest single source of recurrence in children, Dr. del Nido said. A cleft on the anterior leaflet can be particularly vexing. For example, cleft edges attached to the septum can prevent the valve leaflet from coaptation with the posterior leaflet. “If you don’t recognize that on 3-D echocardiography, you’re going to have a problem; that leaflet will never create the coaptation surface that you want,” he said.

The solution may lie underneath the leaflet. Said Dr. del Nido, “We tend to want to close a cleft, and, yes, that will get you relief of regurgitation in the central portion, but if you end up with immobility of that leaflet, then look underneath. Most often there are very abnormal attachments to the edges of that cleft to the septum. You have to get rid of that; if you don’t resect all that, you’ll never have a leaflet that truly floats up to coapt against the posterior leaflet.”

Annular dilation in children can also challenge a cardiothoracic surgeon’s skill.

In rare cases, a suture commissuroplasty may correct the problem. Sometimes Dr. del Nido will use the DeVega suture annuloplasty – “even though it is very much user dependent; it’s very easy in pediatrics to create stenosis with the DeVega.” As an alternative, synthetic ring annuloplasties can confine valve growth and are rarely used.

Dr. del Nido’s preference is to use a hybrid approach of tissue and resorbable material. “The advantage of the resorbable material is that it will go away, but that’s also the problem with the resorbable material,” he said. “Once it does go away, there’s nothing there to support the annulus, so a combination of tissue and resorbable suture is probably the best answer.”

In posterior leaflet deficiency, a patch of pericardium posteriorly can augment the dysfunctional leaflet. You can also use pericardium as an annuloplasty ring. “You can use it circumferentially,” Dr. del Nido said. “It’s a soft ring; you can certainly use this material which is autologous; it does provide strength to the fibrous annulus; it does support that valve; and you do see growth.” He added that bovine pericardium is not ideal for this use.

Dr. del Nido reported no relevant financial relationships.
 

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AT THE 2017 MITRAL VALVE CONCLAVE

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Key clinical point: Operating on mitral valves in pediatric patients must overcome the wide variability in anatomy among young patients and accommodate growth.

Major finding: Strategies that involve a combination of resorbable material with autologous tissue can accomplish repair in most of these patients.

Data source: Review based on Dr. del Nido’s experience.

Disclosures: Dr. del Nido reported having no relevant financial disclosures.

ALTTO follow-up: Dual HER2 blockade may benefit HER2+/HR- tumors

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Wed, 01/04/2023 - 16:47

 

– HER2-positive/HR-negative breast tumors may have a different biology than HER2+/HR+ tumors and may derive more benefit from dual HER2 blockade, according to 5-year results from the phase III ALTTO trial comparing 1 year of adjuvant anti-HER2 therapy with lapatinib and trastuzumab alone, sequentially, or in combination in patients with HER2-positive early breast cancer.

The hazard ratios for this preplanned updated analysis at a median of 6.9 years of follow-up (when all patients had reached 5 years of follow-up) are similar to those from the primary analysis reported at the 2014 ASCO annual meeting and published in the Journal of Clinical Oncology in 2015 (J Clin Oncol. 2015;34:1034-42) at a median clinical follow-up of 4.5 years, Alvaro Moreno-Aspitia, MD, reported at the annual meeting of the American Society of Clinical Oncology.

In the current analysis, the rate of disease-free survival was 85% with combined lapatinib and trastuzumab (L+T), 84% for sequential trastuzumab and lapatinib (T–L), and 82% with T (hazard ratio for disease-free survival was 0.86 for L+T vs. T and 0.93 for T–L vs. T alone,) said Dr. Moreno-Aspitia of Mayo Clinic, Jacksonville, Fla.

“So, at this time, as noted in the primary analysis, there’s no benefit on the primary endpoint in regard to dual HER2 blockade as provided in this clinical trial,” he said.

There also were no significant differences seen in disease-free survival based on chemotherapy timing, he said.

Notably, disease-free survival was similar across treatment groups among patients with HER2+/HR+ tumors (85% for L+T, 85% to T–L, and 83% for T; HRs, 0.91 and 0.90 vs. T, respectively), but, among those with HER2+/HR– tumors, the 6-year disease-free survival difference for L+T (84%) vs. T (80%) was slightly greater (HR, 0.80).

“This is a hypothesis generating observation that also holds that possibly these patients with hormone receptor–negative tumors may derive benefit from dual HER2 blockade,” Dr. Moreno-Aspitia said, noting that this has also been observed in several other trials.

The 6-year overall survival in ALTTO was 93%, 92%, and 91% for L+T, T–L, and T, respectively (HRs for overall survival, 0.86 for L+T vs. T and 0.88 for T–L).

“At this time, there is absolutely no [overall survival] benefit on dual HER2 blockade over single agent trastuzumab. However, it is very rewarding to see that over 90% of the patients who participated in this trial are alive at this longer-term follow-up,” he said.

As for cardiac events, the numbers remained low as in the primary ALTTO analysis, and no new safety signals had emerged.

ALTTO study subjects were 8,381 patients randomized from 946 sites in 44 countries between June 2007 and July 2011. Those in the L+T group received both agents together for 52 weeks; those in the sequential treatment group received T for 12 weeks followed by a 6-week wash-out period, followed by lapatinib for 34 weeks; and those in the trastuzumab arm (the control arm) and the lapatinib arm each received treatment for 52 weeks. In 2011 the lapatinib arm was closed because of futility, and results for that arm are not included in this analysis.

Long-term follow up of participants continues, a large number of correlative studies are ongoing, and final results will be reported when all patients have been followed for at least 10 years, Dr. Moreno-Aspitia said.

The ALTTO trial was sponsored by GlaxoSmithKline and Novartis. Dr. Moreno-Aspitia reported having no disclosures.

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– HER2-positive/HR-negative breast tumors may have a different biology than HER2+/HR+ tumors and may derive more benefit from dual HER2 blockade, according to 5-year results from the phase III ALTTO trial comparing 1 year of adjuvant anti-HER2 therapy with lapatinib and trastuzumab alone, sequentially, or in combination in patients with HER2-positive early breast cancer.

The hazard ratios for this preplanned updated analysis at a median of 6.9 years of follow-up (when all patients had reached 5 years of follow-up) are similar to those from the primary analysis reported at the 2014 ASCO annual meeting and published in the Journal of Clinical Oncology in 2015 (J Clin Oncol. 2015;34:1034-42) at a median clinical follow-up of 4.5 years, Alvaro Moreno-Aspitia, MD, reported at the annual meeting of the American Society of Clinical Oncology.

In the current analysis, the rate of disease-free survival was 85% with combined lapatinib and trastuzumab (L+T), 84% for sequential trastuzumab and lapatinib (T–L), and 82% with T (hazard ratio for disease-free survival was 0.86 for L+T vs. T and 0.93 for T–L vs. T alone,) said Dr. Moreno-Aspitia of Mayo Clinic, Jacksonville, Fla.

“So, at this time, as noted in the primary analysis, there’s no benefit on the primary endpoint in regard to dual HER2 blockade as provided in this clinical trial,” he said.

There also were no significant differences seen in disease-free survival based on chemotherapy timing, he said.

Notably, disease-free survival was similar across treatment groups among patients with HER2+/HR+ tumors (85% for L+T, 85% to T–L, and 83% for T; HRs, 0.91 and 0.90 vs. T, respectively), but, among those with HER2+/HR– tumors, the 6-year disease-free survival difference for L+T (84%) vs. T (80%) was slightly greater (HR, 0.80).

“This is a hypothesis generating observation that also holds that possibly these patients with hormone receptor–negative tumors may derive benefit from dual HER2 blockade,” Dr. Moreno-Aspitia said, noting that this has also been observed in several other trials.

The 6-year overall survival in ALTTO was 93%, 92%, and 91% for L+T, T–L, and T, respectively (HRs for overall survival, 0.86 for L+T vs. T and 0.88 for T–L).

“At this time, there is absolutely no [overall survival] benefit on dual HER2 blockade over single agent trastuzumab. However, it is very rewarding to see that over 90% of the patients who participated in this trial are alive at this longer-term follow-up,” he said.

As for cardiac events, the numbers remained low as in the primary ALTTO analysis, and no new safety signals had emerged.

ALTTO study subjects were 8,381 patients randomized from 946 sites in 44 countries between June 2007 and July 2011. Those in the L+T group received both agents together for 52 weeks; those in the sequential treatment group received T for 12 weeks followed by a 6-week wash-out period, followed by lapatinib for 34 weeks; and those in the trastuzumab arm (the control arm) and the lapatinib arm each received treatment for 52 weeks. In 2011 the lapatinib arm was closed because of futility, and results for that arm are not included in this analysis.

Long-term follow up of participants continues, a large number of correlative studies are ongoing, and final results will be reported when all patients have been followed for at least 10 years, Dr. Moreno-Aspitia said.

The ALTTO trial was sponsored by GlaxoSmithKline and Novartis. Dr. Moreno-Aspitia reported having no disclosures.

 

– HER2-positive/HR-negative breast tumors may have a different biology than HER2+/HR+ tumors and may derive more benefit from dual HER2 blockade, according to 5-year results from the phase III ALTTO trial comparing 1 year of adjuvant anti-HER2 therapy with lapatinib and trastuzumab alone, sequentially, or in combination in patients with HER2-positive early breast cancer.

The hazard ratios for this preplanned updated analysis at a median of 6.9 years of follow-up (when all patients had reached 5 years of follow-up) are similar to those from the primary analysis reported at the 2014 ASCO annual meeting and published in the Journal of Clinical Oncology in 2015 (J Clin Oncol. 2015;34:1034-42) at a median clinical follow-up of 4.5 years, Alvaro Moreno-Aspitia, MD, reported at the annual meeting of the American Society of Clinical Oncology.

In the current analysis, the rate of disease-free survival was 85% with combined lapatinib and trastuzumab (L+T), 84% for sequential trastuzumab and lapatinib (T–L), and 82% with T (hazard ratio for disease-free survival was 0.86 for L+T vs. T and 0.93 for T–L vs. T alone,) said Dr. Moreno-Aspitia of Mayo Clinic, Jacksonville, Fla.

“So, at this time, as noted in the primary analysis, there’s no benefit on the primary endpoint in regard to dual HER2 blockade as provided in this clinical trial,” he said.

There also were no significant differences seen in disease-free survival based on chemotherapy timing, he said.

Notably, disease-free survival was similar across treatment groups among patients with HER2+/HR+ tumors (85% for L+T, 85% to T–L, and 83% for T; HRs, 0.91 and 0.90 vs. T, respectively), but, among those with HER2+/HR– tumors, the 6-year disease-free survival difference for L+T (84%) vs. T (80%) was slightly greater (HR, 0.80).

“This is a hypothesis generating observation that also holds that possibly these patients with hormone receptor–negative tumors may derive benefit from dual HER2 blockade,” Dr. Moreno-Aspitia said, noting that this has also been observed in several other trials.

The 6-year overall survival in ALTTO was 93%, 92%, and 91% for L+T, T–L, and T, respectively (HRs for overall survival, 0.86 for L+T vs. T and 0.88 for T–L).

“At this time, there is absolutely no [overall survival] benefit on dual HER2 blockade over single agent trastuzumab. However, it is very rewarding to see that over 90% of the patients who participated in this trial are alive at this longer-term follow-up,” he said.

As for cardiac events, the numbers remained low as in the primary ALTTO analysis, and no new safety signals had emerged.

ALTTO study subjects were 8,381 patients randomized from 946 sites in 44 countries between June 2007 and July 2011. Those in the L+T group received both agents together for 52 weeks; those in the sequential treatment group received T for 12 weeks followed by a 6-week wash-out period, followed by lapatinib for 34 weeks; and those in the trastuzumab arm (the control arm) and the lapatinib arm each received treatment for 52 weeks. In 2011 the lapatinib arm was closed because of futility, and results for that arm are not included in this analysis.

Long-term follow up of participants continues, a large number of correlative studies are ongoing, and final results will be reported when all patients have been followed for at least 10 years, Dr. Moreno-Aspitia said.

The ALTTO trial was sponsored by GlaxoSmithKline and Novartis. Dr. Moreno-Aspitia reported having no disclosures.

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Key clinical point: HER2+/HR-negative tumors may benefit more than HER2+/HR+ tumors from dual HER2 blockade, according to 5-year results from the phase III ALTTO trial.

Major finding: DFS differed slightly between lapatinib plus trastuzumab and trastuzumab alone (84% vs. 80%; HR, 0.80) among those with HER2+/HR-negative tumors but not among those with HER2+/HR+ tumors.

Data source: The phase III ALTTO trial of 8,381 patients.

Disclosures: The ALTTO trial was sponsored by GlaxoSmithKline and Novartis. Dr. Moreno-Aspitia reported having no disclosures.

AED Choice Requires an Individualized Approach

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Mon, 01/07/2019 - 10:31
Disease management should be based on the needs of the individual patient.

Jacqueline A. French, MD
BOSTON—There is no such thing as a one-size-fits-all approach to epilepsy therapy, according to an overview presented at the 69th Annual Meeting of the American Academy of Neurology. Given the array of available antiepileptic drugs (AEDs), physicians should create a disease management regimen based on the needs of the individual patient, said Jacqueline A. French, MD, Professor of Neurology at New York University. “Not every patient should be started on levetiracetam, although that seems to be a widespread practice around the country,” she said. “We have to think about a number of important questions that will eventually whittle that long list of AEDs to a relatively short list of drugs that are appropriate for a particular patient.” Key factors in selecting a therapy include the patient’s epilepsy syndrome, drug adverse reactions, and other treatment characteristics, such as how long it will take a patient to receive a therapeutic dose and the potential for drug interactions.

New Epilepsy Classification System

A patient’s epilepsy syndrome is the most important factor when choosing an AED, Dr. French said. According to a new epilepsy classification system published by the International League Against Epilepsy, generalized epilepsy may be further categorized as absence, myoclonic, atonic, tonic, and tonic–clonic. Focal epilepsy (formerly called partial epilepsy) may be categorized as focal aware (formerly simple partial), focal impaired awareness (formerly complex partial), and focal to bilateral tonic–clonic (formerly secondary generalized).

Combined generalized and focal epilepsy is a new category associated with epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Finally, “seizures of unknown onset” describes cases where the clinician does not have enough information to determine whether the epilepsy is focal or generalized.

Narrow-spectrum drugs, including carbamazepine, oxcarbazepine, tiagabine, gabapentin, and pregabalin, should only be used in patients with focal epilepsy. “Narrow-spectrum drugs might make generalized seizures worse, or they fail to treat generalized seizures,” Dr. French said. “People with generalized epilepsy, generalized and focal epilepsy combined, or epilepsy of unknown onset should be on broad-spectrum agents—valproic acid, topiramate, lamotrigine, levetiracetam, zonisamide, and perampanel.”

Risk of Adverse Effects

“With any AED, the most common adverse events are dose-related,” Dr. French said. Some adverse events occur during titration and eventually resolve. Some drugs are associated with specific adverse events and therefore should be avoided in certain patient populations.

For instance, carbamazepine, oxcarbazepine, and eslicarbazepine may cause hyponatremia and should be given with caution to at-risk patients, such as the elderly. Likewise, drugs that may cause renal calculi, such as topiramate and zonisamide, should be given with caution to patients with that condition. Enzyme-inducing AEDs that increase cholesterol levels (eg, carbamazepine and phenytoin) should be avoided in patients with cardiovascular risk factors. For patients with weight problems or eating disorders, physicians should bear in mind that valproate, gabapentin, carbamazepine, pregabalin, ezogabine, and perampanel have been known to increase weight, while topiramate, zonisamide, and felbamate have been known to decrease weight.

AEDs that may worsen psychiatric function include levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel. “Make sure that you ask patients when they are on levetiracetam whether they are experiencing increased irritability, although not everyone recognizes their mood changes,” Dr. French said. “Sometimes the spouse will complain, but the person will not.” On the other hand, carbamazepine, valproic acid, lamotrigine, and pregabalin have a tendency to improve psychiatric function—but not always. Psychiatric function “can go either way” with any of the AEDs, she said.

Some patients experience adverse drug effects as a result of add-on therapy. In some cases, a pharmacodynamic interaction between the new and old drugs may be responsible. Removing the add-on drug or the background drug may help. “Sometimes it is a better idea to take away the background drugs,” she said.

Older AEDs—carbamazepine, phenytoin, phenobarbital, and valproic acid—are associated with idiosyncratic adverse effects, including serious rash, liver failure, bone marrow failure, and pancreatitis. While some of the newer drugs also have such risks, the overall rate of idiosyncratic adverse reactions with their use is lower. Thus far, levetiracetam, brivaracetam, gabapentin, and pregabalin have not been associated with major idiosyncratic adverse effects, Dr. French noted.

Drug Initiation and Interactions

“The ability to initiate a drug rapidly is sometimes the driving characteristic that causes some doctors to pick one drug over another,” Dr. French said. Drugs that can be initiated at a therapeutic dose in a single day include phenytoin, levetiracetam, valproic acid, gabapentin, pregabalin, lacosamide, and brivaracetam. Other AEDs, such as carbamazepine, lamotrigine, perampanel, and oxcarbazepine, require gradual initiation over one to 10 weeks. Some drugs that take longer to initiate may be better tolerated overall, she said.

 

 

Generally, older AEDs are more likely to cause drug interactions, compared with newer drugs. Phenytoin, phenobarbital, and carbamazepine are enzyme inducers, which may cause problems for patients who are on statins. Valproic acid is a hepatic enzyme inhibitor, and phenytoin and valproic acid can have protein-binding interactions. Oral contraceptives reduce lamotrigine’s efficacy by doubling the clearance of the AED, Dr. French explained. “This can be problematic when women do not tell you when they are going on and off the contraceptive pill. They can have a breakthrough seizure, and it is only after the fact that you realize why that happened,” she said.

Interactions between oral contraceptive are common with other AEDs, as well. She cited a recent retrospective study involving 1,144 women with epilepsy ages 18 to 47 who provided demographic, epilepsy, AED, contraceptive, and pregnancy data. Survey results showed that 65% of their pregnancies were unintended. Oral forms of contraception had greater failure rates than nonoral forms, with intrauterine devices having the lowest failure rate.

Adriene Marshall

Suggested Reading

Herzog AG, Mandle HB, Cahill KE, et al. Predictors of unintended pregnancy in women with epilepsy. Neurology. 2017;88(8):728-733.

Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521.

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Disease management should be based on the needs of the individual patient.
Disease management should be based on the needs of the individual patient.

Jacqueline A. French, MD
BOSTON—There is no such thing as a one-size-fits-all approach to epilepsy therapy, according to an overview presented at the 69th Annual Meeting of the American Academy of Neurology. Given the array of available antiepileptic drugs (AEDs), physicians should create a disease management regimen based on the needs of the individual patient, said Jacqueline A. French, MD, Professor of Neurology at New York University. “Not every patient should be started on levetiracetam, although that seems to be a widespread practice around the country,” she said. “We have to think about a number of important questions that will eventually whittle that long list of AEDs to a relatively short list of drugs that are appropriate for a particular patient.” Key factors in selecting a therapy include the patient’s epilepsy syndrome, drug adverse reactions, and other treatment characteristics, such as how long it will take a patient to receive a therapeutic dose and the potential for drug interactions.

New Epilepsy Classification System

A patient’s epilepsy syndrome is the most important factor when choosing an AED, Dr. French said. According to a new epilepsy classification system published by the International League Against Epilepsy, generalized epilepsy may be further categorized as absence, myoclonic, atonic, tonic, and tonic–clonic. Focal epilepsy (formerly called partial epilepsy) may be categorized as focal aware (formerly simple partial), focal impaired awareness (formerly complex partial), and focal to bilateral tonic–clonic (formerly secondary generalized).

Combined generalized and focal epilepsy is a new category associated with epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Finally, “seizures of unknown onset” describes cases where the clinician does not have enough information to determine whether the epilepsy is focal or generalized.

Narrow-spectrum drugs, including carbamazepine, oxcarbazepine, tiagabine, gabapentin, and pregabalin, should only be used in patients with focal epilepsy. “Narrow-spectrum drugs might make generalized seizures worse, or they fail to treat generalized seizures,” Dr. French said. “People with generalized epilepsy, generalized and focal epilepsy combined, or epilepsy of unknown onset should be on broad-spectrum agents—valproic acid, topiramate, lamotrigine, levetiracetam, zonisamide, and perampanel.”

Risk of Adverse Effects

“With any AED, the most common adverse events are dose-related,” Dr. French said. Some adverse events occur during titration and eventually resolve. Some drugs are associated with specific adverse events and therefore should be avoided in certain patient populations.

For instance, carbamazepine, oxcarbazepine, and eslicarbazepine may cause hyponatremia and should be given with caution to at-risk patients, such as the elderly. Likewise, drugs that may cause renal calculi, such as topiramate and zonisamide, should be given with caution to patients with that condition. Enzyme-inducing AEDs that increase cholesterol levels (eg, carbamazepine and phenytoin) should be avoided in patients with cardiovascular risk factors. For patients with weight problems or eating disorders, physicians should bear in mind that valproate, gabapentin, carbamazepine, pregabalin, ezogabine, and perampanel have been known to increase weight, while topiramate, zonisamide, and felbamate have been known to decrease weight.

AEDs that may worsen psychiatric function include levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel. “Make sure that you ask patients when they are on levetiracetam whether they are experiencing increased irritability, although not everyone recognizes their mood changes,” Dr. French said. “Sometimes the spouse will complain, but the person will not.” On the other hand, carbamazepine, valproic acid, lamotrigine, and pregabalin have a tendency to improve psychiatric function—but not always. Psychiatric function “can go either way” with any of the AEDs, she said.

Some patients experience adverse drug effects as a result of add-on therapy. In some cases, a pharmacodynamic interaction between the new and old drugs may be responsible. Removing the add-on drug or the background drug may help. “Sometimes it is a better idea to take away the background drugs,” she said.

Older AEDs—carbamazepine, phenytoin, phenobarbital, and valproic acid—are associated with idiosyncratic adverse effects, including serious rash, liver failure, bone marrow failure, and pancreatitis. While some of the newer drugs also have such risks, the overall rate of idiosyncratic adverse reactions with their use is lower. Thus far, levetiracetam, brivaracetam, gabapentin, and pregabalin have not been associated with major idiosyncratic adverse effects, Dr. French noted.

Drug Initiation and Interactions

“The ability to initiate a drug rapidly is sometimes the driving characteristic that causes some doctors to pick one drug over another,” Dr. French said. Drugs that can be initiated at a therapeutic dose in a single day include phenytoin, levetiracetam, valproic acid, gabapentin, pregabalin, lacosamide, and brivaracetam. Other AEDs, such as carbamazepine, lamotrigine, perampanel, and oxcarbazepine, require gradual initiation over one to 10 weeks. Some drugs that take longer to initiate may be better tolerated overall, she said.

 

 

Generally, older AEDs are more likely to cause drug interactions, compared with newer drugs. Phenytoin, phenobarbital, and carbamazepine are enzyme inducers, which may cause problems for patients who are on statins. Valproic acid is a hepatic enzyme inhibitor, and phenytoin and valproic acid can have protein-binding interactions. Oral contraceptives reduce lamotrigine’s efficacy by doubling the clearance of the AED, Dr. French explained. “This can be problematic when women do not tell you when they are going on and off the contraceptive pill. They can have a breakthrough seizure, and it is only after the fact that you realize why that happened,” she said.

Interactions between oral contraceptive are common with other AEDs, as well. She cited a recent retrospective study involving 1,144 women with epilepsy ages 18 to 47 who provided demographic, epilepsy, AED, contraceptive, and pregnancy data. Survey results showed that 65% of their pregnancies were unintended. Oral forms of contraception had greater failure rates than nonoral forms, with intrauterine devices having the lowest failure rate.

Adriene Marshall

Suggested Reading

Herzog AG, Mandle HB, Cahill KE, et al. Predictors of unintended pregnancy in women with epilepsy. Neurology. 2017;88(8):728-733.

Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521.

Jacqueline A. French, MD
BOSTON—There is no such thing as a one-size-fits-all approach to epilepsy therapy, according to an overview presented at the 69th Annual Meeting of the American Academy of Neurology. Given the array of available antiepileptic drugs (AEDs), physicians should create a disease management regimen based on the needs of the individual patient, said Jacqueline A. French, MD, Professor of Neurology at New York University. “Not every patient should be started on levetiracetam, although that seems to be a widespread practice around the country,” she said. “We have to think about a number of important questions that will eventually whittle that long list of AEDs to a relatively short list of drugs that are appropriate for a particular patient.” Key factors in selecting a therapy include the patient’s epilepsy syndrome, drug adverse reactions, and other treatment characteristics, such as how long it will take a patient to receive a therapeutic dose and the potential for drug interactions.

New Epilepsy Classification System

A patient’s epilepsy syndrome is the most important factor when choosing an AED, Dr. French said. According to a new epilepsy classification system published by the International League Against Epilepsy, generalized epilepsy may be further categorized as absence, myoclonic, atonic, tonic, and tonic–clonic. Focal epilepsy (formerly called partial epilepsy) may be categorized as focal aware (formerly simple partial), focal impaired awareness (formerly complex partial), and focal to bilateral tonic–clonic (formerly secondary generalized).

Combined generalized and focal epilepsy is a new category associated with epileptic encephalopathies, such as Dravet syndrome and Lennox-Gastaut syndrome. Finally, “seizures of unknown onset” describes cases where the clinician does not have enough information to determine whether the epilepsy is focal or generalized.

Narrow-spectrum drugs, including carbamazepine, oxcarbazepine, tiagabine, gabapentin, and pregabalin, should only be used in patients with focal epilepsy. “Narrow-spectrum drugs might make generalized seizures worse, or they fail to treat generalized seizures,” Dr. French said. “People with generalized epilepsy, generalized and focal epilepsy combined, or epilepsy of unknown onset should be on broad-spectrum agents—valproic acid, topiramate, lamotrigine, levetiracetam, zonisamide, and perampanel.”

Risk of Adverse Effects

“With any AED, the most common adverse events are dose-related,” Dr. French said. Some adverse events occur during titration and eventually resolve. Some drugs are associated with specific adverse events and therefore should be avoided in certain patient populations.

For instance, carbamazepine, oxcarbazepine, and eslicarbazepine may cause hyponatremia and should be given with caution to at-risk patients, such as the elderly. Likewise, drugs that may cause renal calculi, such as topiramate and zonisamide, should be given with caution to patients with that condition. Enzyme-inducing AEDs that increase cholesterol levels (eg, carbamazepine and phenytoin) should be avoided in patients with cardiovascular risk factors. For patients with weight problems or eating disorders, physicians should bear in mind that valproate, gabapentin, carbamazepine, pregabalin, ezogabine, and perampanel have been known to increase weight, while topiramate, zonisamide, and felbamate have been known to decrease weight.

AEDs that may worsen psychiatric function include levetiracetam, topiramate, zonisamide, tiagabine, phenobarbital, and perampanel. “Make sure that you ask patients when they are on levetiracetam whether they are experiencing increased irritability, although not everyone recognizes their mood changes,” Dr. French said. “Sometimes the spouse will complain, but the person will not.” On the other hand, carbamazepine, valproic acid, lamotrigine, and pregabalin have a tendency to improve psychiatric function—but not always. Psychiatric function “can go either way” with any of the AEDs, she said.

Some patients experience adverse drug effects as a result of add-on therapy. In some cases, a pharmacodynamic interaction between the new and old drugs may be responsible. Removing the add-on drug or the background drug may help. “Sometimes it is a better idea to take away the background drugs,” she said.

Older AEDs—carbamazepine, phenytoin, phenobarbital, and valproic acid—are associated with idiosyncratic adverse effects, including serious rash, liver failure, bone marrow failure, and pancreatitis. While some of the newer drugs also have such risks, the overall rate of idiosyncratic adverse reactions with their use is lower. Thus far, levetiracetam, brivaracetam, gabapentin, and pregabalin have not been associated with major idiosyncratic adverse effects, Dr. French noted.

Drug Initiation and Interactions

“The ability to initiate a drug rapidly is sometimes the driving characteristic that causes some doctors to pick one drug over another,” Dr. French said. Drugs that can be initiated at a therapeutic dose in a single day include phenytoin, levetiracetam, valproic acid, gabapentin, pregabalin, lacosamide, and brivaracetam. Other AEDs, such as carbamazepine, lamotrigine, perampanel, and oxcarbazepine, require gradual initiation over one to 10 weeks. Some drugs that take longer to initiate may be better tolerated overall, she said.

 

 

Generally, older AEDs are more likely to cause drug interactions, compared with newer drugs. Phenytoin, phenobarbital, and carbamazepine are enzyme inducers, which may cause problems for patients who are on statins. Valproic acid is a hepatic enzyme inhibitor, and phenytoin and valproic acid can have protein-binding interactions. Oral contraceptives reduce lamotrigine’s efficacy by doubling the clearance of the AED, Dr. French explained. “This can be problematic when women do not tell you when they are going on and off the contraceptive pill. They can have a breakthrough seizure, and it is only after the fact that you realize why that happened,” she said.

Interactions between oral contraceptive are common with other AEDs, as well. She cited a recent retrospective study involving 1,144 women with epilepsy ages 18 to 47 who provided demographic, epilepsy, AED, contraceptive, and pregnancy data. Survey results showed that 65% of their pregnancies were unintended. Oral forms of contraception had greater failure rates than nonoral forms, with intrauterine devices having the lowest failure rate.

Adriene Marshall

Suggested Reading

Herzog AG, Mandle HB, Cahill KE, et al. Predictors of unintended pregnancy in women with epilepsy. Neurology. 2017;88(8):728-733.

Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512-521.

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New and Noteworthy Information—July 2017

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Device Helps Patients Move Paralyzed Hands After Stroke

Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.

Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].

Pyrimethamine Lowers Levels of ALS Biomarker

Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.

Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].

Statin Use Linked to Higher Risk of Parkinson’s Disease

Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.

Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.

Is Moderate Drinking Associated With Cognitive Decline?

Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.

Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].

Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease

Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.

 

 

Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].

Elevated Brain Amyloid Increases Likelihood of Cognitive Decline

Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.

Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.

Seven Risk Genes for Insomnia Found

Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1, associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample. Sex-specific analyses suggest that the sexes have different genetic architectures, in addition to shared genetic factors. The researchers also found a substantial positive genetic correlation between insomnia complaints and internalizing personality traits and metabolic traits. There was a negative correlation with subjective well-being and educational attainment.

Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].

Is Telemedicine for Headache as Effective as In-Person Visit?

In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.

Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].

Minocycline Reduces Risk of Conversion From CIS to MS

The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.

Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.

Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?

In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.

 

 

Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].

Support From Children Reduces Risk of Dementia

Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.

Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.

Kimberly Williams

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Device Helps Patients Move Paralyzed Hands After Stroke

Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.

Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].

Pyrimethamine Lowers Levels of ALS Biomarker

Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.

Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].

Statin Use Linked to Higher Risk of Parkinson’s Disease

Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.

Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.

Is Moderate Drinking Associated With Cognitive Decline?

Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.

Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].

Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease

Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.

 

 

Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].

Elevated Brain Amyloid Increases Likelihood of Cognitive Decline

Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.

Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.

Seven Risk Genes for Insomnia Found

Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1, associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample. Sex-specific analyses suggest that the sexes have different genetic architectures, in addition to shared genetic factors. The researchers also found a substantial positive genetic correlation between insomnia complaints and internalizing personality traits and metabolic traits. There was a negative correlation with subjective well-being and educational attainment.

Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].

Is Telemedicine for Headache as Effective as In-Person Visit?

In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.

Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].

Minocycline Reduces Risk of Conversion From CIS to MS

The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.

Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.

Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?

In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.

 

 

Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].

Support From Children Reduces Risk of Dementia

Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.

Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.

Kimberly Williams

Device Helps Patients Move Paralyzed Hands After Stroke

Patients with stroke who learn to use their minds to open and close a device fitted over their paralyzed hands gain some control over their hands, according to a study published online ahead of print May 26 in Stroke. Ten survivors of chronic hemiparetic stroke with moderate-to-severe upper-limb motor impairment used a powered exoskeleton that opened and closed the affected hand using spectral power from EEG signals from the unaffected hemisphere associated with imagined hand movements of the paretic limb. At 12 weeks, participants had a statistically significant average increase of 6.2 points in the Action Research Arm Test. This behavioral improvement significantly correlated with improvements in brain–computer interface control. Secondary outcomes of grasp strength, Motricity Index, and the Canadian Occupational Performance Measure also significantly improved.

Bundy DT, Souders L, Baranyai K, et al. Contralesional brain-computer interface control of a powered exoskeleton for motor recovery in chronic stroke survivors. Stroke. 2017 May 26 [Epub ahead of print].

Pyrimethamine Lowers Levels of ALS Biomarker

Pyrimethamine is safe and well tolerated in amyotrophic lateral sclerosis (ALS), according to a study published online ahead of print May 8 in Annals of Neurology. Participants underwent a multicenter, open-label, nine-month dose-ranging study to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in patients with SOD1 mutations linked to familial ALS. The study included 32 patients with various SOD1 genetic mutations linked to ALS. Participants had three lumbar punctures, blood studies, and a clinical assessment of strength, motor function, quality of life, and potential adverse effects. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit six, with a mean reduction of 13.5%, and at visit nine, with a mean reduction of 10.5%.

Lange DJ, Shahbazi M, Silani V, et al. Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations. Ann Neurol. 2017 May 8 [Epub ahead of print].

Statin Use Linked to Higher Risk of Parkinson’s Disease

Statins, especially lipophilic statins, are associated with higher risk of Parkinson’s disease, according to a study published in the June issue of Movement Disorders. The association is stronger with initial use, which suggests a facilitating effect, said the investigators. Researchers performed a retrospective case–control analysis and identified 2,322 people with incident Parkinson’s disease who had been enrolled in a claims database for at least 2.5 years before diagnosis or prescription of antiparkinson medication. They matched the cases with 2,322 controls by age, gender, and a follow-up window. Statin use was significantly associated with Parkinson’s disease risk. The strongest associations were for lipophilic statins (odds ratio [OR], 1.58) versus hydrophilic statins (OR, 1.19), statins plus nonstatins (OR, 1.95), and for the initial period after starting statins.

Liu G, Sterling NW, Kong L, et al. Statins may facilitate Parkinson’s disease: insight gained from a large, national claims database. Mov Disord. 2017;32(6):913-917.

Is Moderate Drinking Associated With Cognitive Decline?

Moderate alcohol consumption is associated with adverse brain outcomes, including hippocampal atrophy, according to a study published online ahead of print June 6 in BMJ. The study included 550 men and women with a mean age of 43 at study baseline. No patient had alcohol dependence, and all underwent brain MRI at follow-up. Higher alcohol consumption over the 30-year follow-up was associated with increased odds of hippocampal atrophy in a dose-dependent fashion. People consuming more than 30 units/week of alcohol were at the highest risk, compared with abstainers. People who drank moderately had three times the odds of right-sided hippocampal atrophy. There was no protective effect of light drinking over abstinence. Higher alcohol use also was associated with differences in corpus callosum microstructure and faster decline in lexical fluency.

Topiwala A, Allan CL, Valkanova V, et al. Moderate alcohol consumption as risk factor for adverse brain outcomes and cognitive decline: longitudinal cohort study. BMJ. 2017 Jun 6 [Epub ahead of print].

Consuming Low-Fat Dairy May Increase Risk for Parkinson’s Disease

Frequently consuming low-fat dairy products may be associated with an increased risk of Parkinson’s disease, according to a study published online ahead of print June 8 in Neurology. This study is based on data from 80,736 participants in the Nurses’ Health Study and 48,610 participants in the Health Professionals Follow-Up Study, with 26 and 24 years of follow-up, respectively. Both US-based studies were conducted through mailed biennial questionnaires. Dietary intake was assessed with food frequency questionnaires administered repeatedly over the follow-up period. Total dairy intake was not significantly associated with Parkinson’s disease risk, but intake of low-fat dairy foods was associated with Parkinson’s disease risk. This association appeared to result from an increased risk of Parkinson’s disease associated with skim and low-fat milk.

 

 

Hughes KC, Gao X, Kim IY, et al. Intake of dairy foods and risk of Parkinson disease. Neurology. 2017 Jun 8 [Epub ahead of print].

Elevated Brain Amyloid Increases Likelihood of Cognitive Decline

Elevated baseline brain amyloid level, compared with normal brain amyloid level, is associated with higher likelihood of cognitive decline, according to a study published June 13 in JAMA. Exploratory analyses were conducted with longitudinal cognitive and biomarker data from 445 cognitively normal people. Participants were classified at baseline as having normal or elevated brain amyloid using PET amyloid imaging or a CSF assay of amyloid β. Outcomes included scores on the Preclinical Alzheimer Cognitive Composite (PACC), Mini-Mental State Examination (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-SOB), and Logical Memory Delayed Recall. Compared with the group with normal amyloid, people with elevated amyloid had worse mean scores at four years on the PACC, MMSE, and CDR-SOB. For Logical Memory Delayed Recall, between-group scores were not significantly different at four years.

Donohue MC, Sperling RA, Petersen R, et al. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA. 2017;317(22):2305-2316.

Seven Risk Genes for Insomnia Found

Researchers have found seven risk genes for insomnia, according to a study published online ahead of print June 12 in Nature Genetics. To identify genetic factors for insomnia complaints, investigators performed a genome-wide association study and a genome-wide gene-based association study in 113,006 participants. The authors identified three loci and seven genes, including MEIS1, associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample. Sex-specific analyses suggest that the sexes have different genetic architectures, in addition to shared genetic factors. The researchers also found a substantial positive genetic correlation between insomnia complaints and internalizing personality traits and metabolic traits. There was a negative correlation with subjective well-being and educational attainment.

Hammerschlag AR, Stringer S, de Leeuw CA, et al. Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits. Nat Genet. 2017 Jun 12 [Epub ahead of print].

Is Telemedicine for Headache as Effective as In-Person Visit?

In people with headache, a video consultation with a neurologist for treatment may be as effective as an in-person visit, according to a study published online ahead of print June 14 in Neurology. Researchers randomized, allocated, and consulted patients with nonacute headache via telemedicine or in a traditional manner in a noninferiority trial. Efficacy end points assessed by questionnaires at three and 12 months included change from baseline in Headache Impact Test-6 (HIT-6) and pain intensity. The primary safety end point was presence of secondary headache within 12 months after consultation. There were no differences between telemedicine and traditional consultations in HIT-6 or pain intensity over three periods. The absolute difference in HIT-6 from baseline was 0.3 at three months and 0.2 at 12 months.

Müller KI, Alstadhaug KB, Bekkelund SI. A randomized trial of telemedicine efficacy and safety for nonacute headaches. Neurology. 2017 Jun 14 [Epub ahead of print].

Minocycline Reduces Risk of Conversion From CIS to MS

The risk of conversion from clinically isolated syndrome (CIS) to multiple sclerosis (MS) is significantly lower with minocycline than with placebo over six months, but not over 24 months, according to a study published June 1 in the New England Journal of Medicine. This study included 142 participants who had had their first demyelinating symptoms within the previous 180 days. At 12 Canadian MS clinics, researchers randomly assigned participants to receive either 100 mg of minocycline, administered orally twice daily, or placebo. Administration of minocycline or placebo was continued until a diagnosis of MS was established or until 24 months after randomization. The unadjusted risk of conversion to MS within six months after randomization was 61.0% in the placebo group and 33.4% in the minocycline group.

Metz LM, Li DKB, Traboulsee AL, et al. Trial of minocycline in a clinically isolated syndrome of multiple sclerosis. N Engl J Med. 2017;376(22):2122-2133.

Can Gene Mutation Speed Memory Loss in Alzheimer’s Disease?

In a middle-aged cohort with Alzheimer’s disease risk, the BDNF Met allele is associated with steeper decline in episodic memory and executive function, according to a study published online ahead of print May 3 in Neurology. One thousand twenty-three adults enrolled in the Wisconsin Registry for Alzheimer’s Prevention underwent BDNF genotyping and cognitive assessment at as many as five time points. A subset of participants underwent Pittsburgh compound B scanning. Compared with BDNF Val/Val homozygotes, Met carriers had steeper decline in verbal learning and memory, and in speed and flexibility. In addition, amyloid β burden moderated the relationship between BDNF and verbal learning and memory, such that Met carriers with greater amyloid β burden showed even steeper cognitive decline.

 

 

Boots EA, Schultz SA, Clark LR, et al. BDNF Val66Met predicts cognitive decline in the Wisconsin Registry for Alzheimer’s Prevention. Neurology. 2017 May 3 [Epub ahead of print].

Support From Children Reduces Risk of Dementia

Positive social support from children is associated with reduced risk of dementia, whereas negative social support from children and other immediate family increases the risk, according to a study published in the Journal of Alzheimer’s Disease. Researchers analyzed 10-year follow-up data in 10,055 cognitively normal participants age 50 and older from the English Longitudinal Study of Aging. Incidence of dementia was identified from participant- or informant-reported physician diagnosed dementia or overall score of informant-completed IQCODE questionnaire. Positive social support from children significantly reduced the risk of dementia (hazard ratio, 0.83). Negative support from family and friends was significantly associated with increased risk of dementia. The causal mechanisms that create these associations require further research, said the researchers.

Khondoker M, Rafnsson SB, Morris S, et al. Positive and negative experiences of social support and risk of dementia in later life: an investigation using the English Longitudinal Study of Ageing. J Alzheimers Dis. 2017;58(1):99-108.

Kimberly Williams

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T receptor diversity may predict BCP-ALL response to blinatumomab

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– For patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), an extensive and diverse T-cell receptor repertoire may be predictive of response to blinatumomab (Blincyto), investigators suggest.

Nancy B. Baron/Frontline Medical News
Dr. Michaela Kotrova
“The diversity of T lymphocytes is really important for the type of immune system against leukemia,” she said at a briefing at the annual congress of the European Hematology Association.

Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. Although it can induce high remission rates in patients with relapsed/refractory BCP-ALL and has been shown to nearly double overall survival among patients with relapsed/refractory BCP-ALL negative for the Philadelphia chromosome, about half of patients do not achieve a minimal residual disease response. This finding prompted the investigators to determine whether differences in the TRB repertoire could have an effect on individual patient responses to blinatumomab.

They performed next-generation sequencing of immunoglobulin and T-cell receptor gene rearrangements to evaluate the diversity of the repertoire, which can have a profound impact on health.

Dr. Kotrova noted that, in young people, there may be as many as 120 million different TRB gene rearrangements, and the more the merrier because a higher diversity repertoire is capable of protecting people from a large variety of pathogens.

They compared the diversity of the TRB repertoire in 114 patients who were either responders to blinatumomab salvage therapy or who had measurable minimal residual disease (persisters).

They found that there was significantly greater probability than mere chance that the TRB repertoire before blinatumomab administration was more diverse in patients with responses, compared with those without responses.

On day 15 of the first cycle of blinatumomab therapy, there was no significant difference in TRB repertoire between responders and persisters, but, by day 29, there was a sharper and statistically significant increase in repertoire diversity but no significant increase among nonresponders.

Their findings raise the intriguing possibility that response to blinatumomab could be predicted by repertoire diversity prior to the start of therapy, but further studies with larger patient cohorts will be necessary to confirm this, Dr. Kotrova said.

The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.

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– For patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), an extensive and diverse T-cell receptor repertoire may be predictive of response to blinatumomab (Blincyto), investigators suggest.

Nancy B. Baron/Frontline Medical News
Dr. Michaela Kotrova
“The diversity of T lymphocytes is really important for the type of immune system against leukemia,” she said at a briefing at the annual congress of the European Hematology Association.

Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. Although it can induce high remission rates in patients with relapsed/refractory BCP-ALL and has been shown to nearly double overall survival among patients with relapsed/refractory BCP-ALL negative for the Philadelphia chromosome, about half of patients do not achieve a minimal residual disease response. This finding prompted the investigators to determine whether differences in the TRB repertoire could have an effect on individual patient responses to blinatumomab.

They performed next-generation sequencing of immunoglobulin and T-cell receptor gene rearrangements to evaluate the diversity of the repertoire, which can have a profound impact on health.

Dr. Kotrova noted that, in young people, there may be as many as 120 million different TRB gene rearrangements, and the more the merrier because a higher diversity repertoire is capable of protecting people from a large variety of pathogens.

They compared the diversity of the TRB repertoire in 114 patients who were either responders to blinatumomab salvage therapy or who had measurable minimal residual disease (persisters).

They found that there was significantly greater probability than mere chance that the TRB repertoire before blinatumomab administration was more diverse in patients with responses, compared with those without responses.

On day 15 of the first cycle of blinatumomab therapy, there was no significant difference in TRB repertoire between responders and persisters, but, by day 29, there was a sharper and statistically significant increase in repertoire diversity but no significant increase among nonresponders.

Their findings raise the intriguing possibility that response to blinatumomab could be predicted by repertoire diversity prior to the start of therapy, but further studies with larger patient cohorts will be necessary to confirm this, Dr. Kotrova said.

The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.

 

– For patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), an extensive and diverse T-cell receptor repertoire may be predictive of response to blinatumomab (Blincyto), investigators suggest.

Nancy B. Baron/Frontline Medical News
Dr. Michaela Kotrova
“The diversity of T lymphocytes is really important for the type of immune system against leukemia,” she said at a briefing at the annual congress of the European Hematology Association.

Blinatumomab is a bispecific T-cell engager designed to direct cytotoxic T cells to cancer cells expressing the CD19 receptor. Although it can induce high remission rates in patients with relapsed/refractory BCP-ALL and has been shown to nearly double overall survival among patients with relapsed/refractory BCP-ALL negative for the Philadelphia chromosome, about half of patients do not achieve a minimal residual disease response. This finding prompted the investigators to determine whether differences in the TRB repertoire could have an effect on individual patient responses to blinatumomab.

They performed next-generation sequencing of immunoglobulin and T-cell receptor gene rearrangements to evaluate the diversity of the repertoire, which can have a profound impact on health.

Dr. Kotrova noted that, in young people, there may be as many as 120 million different TRB gene rearrangements, and the more the merrier because a higher diversity repertoire is capable of protecting people from a large variety of pathogens.

They compared the diversity of the TRB repertoire in 114 patients who were either responders to blinatumomab salvage therapy or who had measurable minimal residual disease (persisters).

They found that there was significantly greater probability than mere chance that the TRB repertoire before blinatumomab administration was more diverse in patients with responses, compared with those without responses.

On day 15 of the first cycle of blinatumomab therapy, there was no significant difference in TRB repertoire between responders and persisters, but, by day 29, there was a sharper and statistically significant increase in repertoire diversity but no significant increase among nonresponders.

Their findings raise the intriguing possibility that response to blinatumomab could be predicted by repertoire diversity prior to the start of therapy, but further studies with larger patient cohorts will be necessary to confirm this, Dr. Kotrova said.

The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.

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Key clinical point: T-cell receptor–beta diversity is important for protection against a wide variety of pathogens.

Major finding: Patients with responses to blinatumomab had a significantly more diverse TRB gene repertoire at the time of screening, compared with patients who would go on to have minimal residual disease after starting on blinatumomab therapy.

Data source: A next-generation sequencing study of samples from 114 patients with relapsed/refractory B-cell precursor acute lymphocytic leukemia.

Disclosures: The study was supported by Amgen. Dr. Kotrova had no relevant disclosures.

Dermatologist calls for paradigm shift on treating ocular rosacea

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A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.

“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.

Dr. Kara Capriotti
An estimated 16 million people in the United States have rosacea, according to the National Rosacea Society, and researchers have estimated that rosacea affects the eye in 58%-72% of patients (US Ophthalmic Review. 2013;6[2]:86-8). A 2016 Rosacea Society survey of 615 people with rosacea found that up to 92% reported eye symptoms that included irritation, grittiness, or dryness, and 86% reported watery or bloodshot eyes – symptoms that most said started after they developed rosacea. That said, 72% said they had never been treated specifically for ocular rosacea.

Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.

Rosacea.org
Subtype 4 ocular rosacea: Eye irritation: Watery or bloodshot appearance, irritation, burning or stinging.
Dr. Capriotti, who practices in Rosemont, Pa., began developing topical treatments with colleagues who have backgrounds in drug development and ophthalmology, considering the eyelid skin as a target. “The idea of treating blepharitis/ocular rosacea through the skin comes directly out of this progression and the collaboration between a dermatologist looking at the disease as a skin disease and the ophthalmologists ... seeing a new way to think about an ocular surface problem that has its root cause in the lid,” she explained in an interview.

The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”

Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.

In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.

After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”

DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).

There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.

Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”

She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.

Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.

 

 

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A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.

“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.

Dr. Kara Capriotti
An estimated 16 million people in the United States have rosacea, according to the National Rosacea Society, and researchers have estimated that rosacea affects the eye in 58%-72% of patients (US Ophthalmic Review. 2013;6[2]:86-8). A 2016 Rosacea Society survey of 615 people with rosacea found that up to 92% reported eye symptoms that included irritation, grittiness, or dryness, and 86% reported watery or bloodshot eyes – symptoms that most said started after they developed rosacea. That said, 72% said they had never been treated specifically for ocular rosacea.

Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.

Rosacea.org
Subtype 4 ocular rosacea: Eye irritation: Watery or bloodshot appearance, irritation, burning or stinging.
Dr. Capriotti, who practices in Rosemont, Pa., began developing topical treatments with colleagues who have backgrounds in drug development and ophthalmology, considering the eyelid skin as a target. “The idea of treating blepharitis/ocular rosacea through the skin comes directly out of this progression and the collaboration between a dermatologist looking at the disease as a skin disease and the ophthalmologists ... seeing a new way to think about an ocular surface problem that has its root cause in the lid,” she explained in an interview.

The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”

Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.

In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.

After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”

DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).

There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.

Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”

She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.

Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.

 

 

 

A partnership between ophthalmologists and dermatologists holds the potential to produce a better treatment for ocular rosacea, one of the few conditions that brings the two specialties together.

“Hopefully, the paradigm eventually shifts from treating symptoms and signs of ocular rosacea with oral antibiotics or reflexive referral to ophthalmology to approaching cutaneous treatment first,” said dermatologist Kara Capriotti, MD, who has been working with a team of ophthalmologists to develop a treatment that focuses on ocular rosacea as a “lid disease,” instead of as a primary ocular surface problem.

Dr. Kara Capriotti
An estimated 16 million people in the United States have rosacea, according to the National Rosacea Society, and researchers have estimated that rosacea affects the eye in 58%-72% of patients (US Ophthalmic Review. 2013;6[2]:86-8). A 2016 Rosacea Society survey of 615 people with rosacea found that up to 92% reported eye symptoms that included irritation, grittiness, or dryness, and 86% reported watery or bloodshot eyes – symptoms that most said started after they developed rosacea. That said, 72% said they had never been treated specifically for ocular rosacea.

Eye scrubs, artificial tears, stress relief measures, and antibiotics are among the treatments used for the condition, which, however, can be treatment-resistant.

Rosacea.org
Subtype 4 ocular rosacea: Eye irritation: Watery or bloodshot appearance, irritation, burning or stinging.
Dr. Capriotti, who practices in Rosemont, Pa., began developing topical treatments with colleagues who have backgrounds in drug development and ophthalmology, considering the eyelid skin as a target. “The idea of treating blepharitis/ocular rosacea through the skin comes directly out of this progression and the collaboration between a dermatologist looking at the disease as a skin disease and the ophthalmologists ... seeing a new way to think about an ocular surface problem that has its root cause in the lid,” she explained in an interview.

The key, she believes, is to move from a focus on ocular symptoms to an emphasis on lid and skin signs associated with ocular rosacea. “Almost all of the ophthalmology approaches to the disease start at the ocular surface, and these surface treatments are always a little bit [or very] toxic to the ocular surface,” she said. “By treating the lid signs first through a topical approach through the closed lid, we can eliminate a lot of the ocular surface symptoms without ever touching the ocular surface, thus preventing a lot of the associated toxicity and side effects you commonly see with topical ophthalmics.”

Dr. Capriotti and her colleagues have developed a topical treatment that contains dimethyl sulfoxide (DMSO) combined with dilute povidone iodine, which is applied to the lid margin of the closed eye.

In 2015, they published a case report describing the successful use of the treatment for a 78-year-old man with rosacea blepharoconjunctivitis, who had failed oral and topical treatments. He was treated with povidone iodine 10% solution in a DMSO vehicle, which was compounded into a topical gel by a pharmacy and administered twice a day, rubbed onto the lash line and eyelid.

After one week, “remarkable improvements were noted,” with reversal of much of the conjunctivitis, anterior lid erythema, and thickening, they wrote. One month later, after once daily application, “not only were the initial improvements conserved, but the posterior lid margin vessels and telangiectasias had begun to attenuate and involute. Moreover, meibomian capping was no longer present, secretions were less viscous, and tear break-up time normalized.”

DMSO is a skin penetration agent that is rarely used in ophthalmology and povidone iodine is a biocidal agent used in eye care, they pointed out in the case report. “This novel therapy may warrant further investigation in randomized, controlled clinical trials,” they concluded (Ophthalmol Ther. 2015 Dec;4[2]:143-50).

There are plans to start a clinical trial later in 2017, according to Dr. Capriottis, the cofounder of Veloce Biopharma, a company that is developing this product.

Until more specific treatments are available, what can dermatologists do now to improve their care of patients with ocular rosacea? “First and foremost, you have to be comfortable looking at the eyelids and ruling out anything that could be masquerading as blepharitis,” Dr. Capriotti commented. “We have a big disadvantage in dermatology because we don’t use slit-lamp biomicroscopy, but we are pretty good at looking at skin. If the patient has a lot of extraocular rosacea signs, I definitely think dermatologists can manage the prescription of a topical for the lids and evaluate the response.”

She cautioned, however, that referrals are in order in several situations: cases that are severe, those that involve the eye only, and those with which ocular symptoms seem to outweigh the lid signs.

Dr. Capriotti is also the senior vice president of dermatology at Veloce. In the study published in 2015, she and her three coauthors disclosed having financial interest in ALC Therapeutics, a company that was dissolved and restructured into Veloce.

 

 

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